Cat's Claws and
shark cartilage/ Una de Gato
y Cartilago de Tiburon.
Data-Medicos
Dermagic/Express No. 2-(90)
08 Marzo 2.000 08 March 2.000
~ Una de gato y Cartilago de Tiburon ~
~ Cat's Claw and Shark Cartilage ~
EDITORIAL ESPANOL
=================
Hola amigos de la Red, DERMAGIC de nuevo con ustedes. Hoy un
tema NO DERMATOLOGICO bastante interesante. LA UÑA DE GATO Y EL
CARTILAGO DE TIBURON.
LA UÑA DE GATO no es en realidad " la uña de un gato",
se trata de una planta originaria del PERU llamada UNCARIA TOMENTOSA, a
la cual se le han descubierto algunas acciones beneficas para el organismo,
pudiendo ser utilizada en: artritis, reumatismo, bursitis, gota, deficiencias
inmunologicas, permeabilidad intestinal, intoxicaciones, y CANCER, inhibe la
agregacion plaquetaria y actua como anti-inflamatorio. Esta
de moda hoy dia el uso de la UNCARIA TOMENTOSA como coadyuvante a diversos
tratamientos.
EL CARTILAGO DE TIBURON no se queda atras, tiene efectos ANTI-TUMORALES
y ANTI-ANGIOGENESIS comprobados cientificamente, incluso se ha sugerido
su utilización en la PSORIASIS (referencia 25). Otros efectos incluyen:
anti-inflamatorio, analgesico, y supresor de la aterogenesis.
Lo cierto es que estos productos, al igual que el ginkgo biloba,
Pygeum Africanum, Saw palmeto y otros, hoy en dia son una veridica muestra
de que estas medicinas ALTERNATIVAS estan ocupando un lugar importante
en nuestro MUNDO CIENTIFICO.
En las referencias Los Hechos ...
Dr Jose Lapenta R.
EDITORIAL ENGLISH
=================
Hello friends of the Net, DERMAGIC again with you. Today a quite interesting
NON DERMATOLOGIC topic. THE CAT'S CLAW AND THE SHARK CARTILAGE.
THE CAT'S CLAW is not in fact the "fingernail of a cat", it is a plant
from PERU called UNCARIA TOMENTOSA, to which have been discovered
some beneficent actions for the organism, being able to be used in: arthritis,
rheumatism, bursitis, gout, immunologic deficiencies, intestinal permeability,
intoxications, AND CANCER, it inhibits the platelet aggregation and it acts as anti-inflammatory.
This in fashion nowadays the use of the UNCARIA TOMENTOSA like helping
to diverse treatments.
THE SHARK CARTILAGE doesn't lag behind, he has effects scientifically
proven ANTI-TUMOR and ANTI ANGIOGENESIS activities, its use has even been
suggested in PSORIASIS (reference 25). Other effects include: anti-inflammatory,
analgesic, and suppression of atherogenesis.
The really TRUTH is that these products, the same as the ginkgo biloba,
Pygeum Africanum, Saw palmeto and other, today in day they are a truthful
sample that that these ALTERNATIVE medicines are occupying an important
place in our SCIENTIFIC WORLD.
In the references, The facts,
Dr. Jose Lapenta R.
=============================================================
BIBLIOGRAPHICAL REFERENCES / REFERENCIAS BIBLIOGRAFICAS
=============================================================
1.) Enhanced DNA repair, immune function and reduced toxicity of C-MED-100,
a novel aqueous extract from Uncaria tomentosa.
2.) Uncaria tomentosa (Willd.) D.C.: cat's claw, una de gato, or saventaro.
3.) Stimulation of interleukin-1 and -6 production in alveolar macrophages
by the neotropical liana, Uncaria tomentosa (una de gato).
4.) Uncaria tomentosa (Willd.) DC.--ethnomedicinal use and new pharmacological,
toxicological and botanical results.
5.) Induction of apoptosis and inhibition of proliferation in human
tumor cells treated with extracts of Uncaria tomentosa.
6.) Evaluation of the toxicity of Uncaria tomentosa by bioassays in
vitro.
7.) Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human
endothelial cells to release a lymphocyte-proliferation-regulating factor.
8.) Depletion of specific binding sites for estrogen receptor by Uncaria
tomentosa.
9.) Antiinflammatory actions of cat's claw: the role of NF-kappaB.
10.) Mutagenic and antimutagenic activities of Uncaria tomentosa and
its extracts.
11.) Plant metabolites. New compounds and anti-inflammatory activity
of Uncaria tomentosa.
12.) New polyhydroxylated triterpenes from Uncaria tomentosa.
13.) Plant metabolites. Structure and in vitro antiviral activity of
quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda.
14.) [Phytochemical and biological study of Uncaria tomentosa].
15.) The alkaloids of Uncaria tomentosa and their phagocytosis-stimulating
action].
16.) CAT'S CLAW (Una de Gato) #K725 INGREDIENTS:
=============================================================
CARTILAGO DE TIBURON / SHARK CARTILAGE
=============================================================
17.) How useful are unconventional cancer treatments?
18.) A monoclonal antibody which recognizes a glycosaminoglycan epitope
in both dermatan sulfate and chondroitin sulfate proteoglycans of human
skin.
19.) [The national cancer fund (Koningin Wilhelmina Fonds) and the
Houtsmuller-therapy for cancer].
20.) Effect of U-995, a potent shark cartilage-derived angiogenesis
inhibitor, on anti-angiogenesis and anti-tumor activities.
21.) Shark cartilage-containing preparation: protection against reactive
oxygen species.
22.) The effect of shark cartilage extracts on the growth and metastatic
spread of the SCCVII carcinoma.
23.) Phase I/II trial of the safety and efficacy of shark cartilage
in the treatment of advanced cancer.
24.) Occurrence of a novel collagen with three distinct chains in the
cranial cartilage of the squid Sepia officinalis: comparison with shark
cartilage collagen.
25.) Antiangiogenic properties of a novel shark cartilage extract:
potential role in the treatment of psoriasis.
26.) Dietary supplement use by women at risk for breast cancer recurrence.
The Women's Healthy Eating and Living Study Group.
27.) The analgesic and anti-inflammatory effects of shark cartilage
are due to a peptide molecule and are nitric oxide (NO) system dependent.
28.) Shark cartilage-induced hepatitis.
29.) Anti-inflammatory and analgesic activity of a water-soluble fraction
from shark cartilage.
30.) Shark-cartilage containing preparation protects cells against
hydrogen peroxide induced damage and mutagenesis.
31.) McGuire TR, Kazakoff PW, Hoie EB, Fienhold MA
Department of Pharmacy Practice, University of Nebraska,
32.) Demonstration of immunogenic keratan sulphate in commercial chondroitin
6-sulphate from shark cartilage. Implications for ELISA assays.
33.) Production and characterization of monoclonal antibodies to shark
cartilage proteoglycan.
34.) Differential effects of glycosaminoglycans on neurite outgrowth
from hippocampal and thalamic neurones.
35.) Structural studies on sulfated oligosaccharides derived from the
carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans
of shark cartilage. II. Seven compounds containing 2 or 3 sulfate residues.
36.) Structural studies on sulfated oligosaccharides derived from the
carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans
of shark cartilage. I. Six compounds containing 0 or 1 sulfate and/or phosphate
residues.
37.) In vitro control of neuronal polarity by glycosaminoglycans.
38.) A novel angiogenic inhibitor derived from Japanese shark cartilage
(I). Extraction and estimation of inhibitory activities toward tumor and
embryonic angiogenesis.
39.) Determination of the distribution of constituent disaccharide
units within the chain near the linkage region of shark-cartilage chondroitin
sulfate C.
40.) Suppression of atherogenesis in hypercholesterolemic rabbits by
chondroitin-6-sulfate.
41.) High-field n.m.r. studies of keratan sulphates. 1H and 13C assignments
of keratan sulphate from shark cartilage.
42.) Ultrastructural cytochemistry of proteoglycans associated with
calcification of shark cartilage.
43.) Distribution of different molecular species of collagen in the
vertebral cartilage of shark (Carcharius acutus).
44.) Shark cartilage contains inhibitors of tumor angiogenesis.
45.) Galactose 6-sulfate sulfatase activity in Morquio syndrome.
46.) Comparative studies of water sorption of hyaline cartilage.
47.) Structure of chondroitin sulfates. Analyses of the products formed
from chondroitin sulfates A and C by the action of the chondroitinases
C and AC from Flavobacterium heparinum.
============================================================
UÑA DE GATO / CAT'S CLAW
=============================================================
1.) Enhanced DNA repair, immune function and reduced toxicity of C-MED-100,
a novel aqueous extract from Uncaria tomentosa.
=============================================================
J Ethnopharmacol 2000 Feb;69(2):115-126 (ISSN: 0378-8741)
Sheng Y [Find other articles with this Author]
Department of Cell and Molecular Biology, University of Lund, Sweden.
[email protected].
Female W/Fu rats were gavaged daily with a water-soluble extract (C-MED-100)
of Uncaria tomentosa supplied commercially by CampaMed at the doses of
0, 5, 10, 20, 40 and 80 mg/kg for 8 consecutive weeks. Phytohemagglutinin
(PHA) stimulated lymphocyte proliferation was significantly increased in
splenocytes of rats treated at the doses of 40 and 80 mg/kg. White blood
cells (WBC) from the C-MED-100 treatment groups of 40 and 80 mg/kg for
8 weeks or 160 mg/kg for 4 weeks were significantly elevated compared with
controls (P < 0.05). In a human volunteer study, C-MED-100 was given
daily at 5 mg/kg for 6 consecutive weeks to four healthy adult males. No
toxicity was observed and again, WBC were significantly elevated (P <
0.05) after supplement. Repair of DNA single strand breaks (SSB) and double
strand breaks (DSB) 3 h after 12 Gy whole body irradiation of rats were
also significantly improved in C-MED-100 treated animals (P < 0.05).
The LD50 and MTD of a single oral dose of C-MED-100 in the rat were observed
to be greater than 8 g/kg. Although the rats were treated daily with U.
tomentosa extracts at the doses of 10-80 mg/kg for 8 weeks or 160 mg/kg
for 4 weeks, no acute or chronic toxicity signs were observed symptomatically.
In addition, no body weight, food consumption, organ weight and kidney,
liver, spleen, and heart pathological changes were found to be associated
with C-MED-100 treatment.
=============================================================
2.) Uncaria tomentosa (Willd.) D.C.: cat's claw, una de gato, or saventaro.
=============================================================
J Altern Complement Med 1999 Apr;5(2):143-51 (ISSN: 1075-5535)
Reinhard KH [Find other articles with this Author]
Apotheke am Oswaldgarten, Giessen, Germany.
Recently, Uncaria tomentosa (Willd.) D.C. has become known as a healing
plant with an ethnomedicinal background. There have been several reports
on its constituents, in particular, oxindole alkaloids. It was found that
2 chemotypes of Uncaria tomentosa with different alkaloid patterns occur
in nature. The roots of one type contain pentacyclic oxindoles and the
other contains tetracyclic oxindoles. This difference should be considered
when the plant is to be used for medicinal applications. Tetracyclic oxindole
alkaloids act on the central nervous system, whereas pentacyclic oxindole
alkaloids affect the cellular immune system. Recent studies have shown
that the tetracyclic alkaloids exert antagonistic effects on the action
of the pentacyclic alkaloids. Mixtures of these 2 types of drugs are therefore
unsuitable for medicinal uses.
=============================================================
3.) Stimulation of interleukin-1 and -6 production in alveolar macrophages
by the neotropical liana, Uncaria tomentosa (una de gato).
=============================================================
J Ethnopharmacol 1999 Feb;64(2):109-15 (ISSN: 0378-8741)
Lemaire I; Assinewe V; Cano P; Awang DV; Arnason JT [Find other articles
with these Authors]
Department of Cellular and Molecular Medicine, University of Ottawa,
Ont., Canada.
Two extracts of different collections of the traditional medicine una
de gato (Uncaria tomentosa) from Peru were characterized by High Pressure
Liquid Chromatography as containing approximately 6 mg/g total oxindole
content prior to studies with alveolar macrophages. The plant preparations
greatly stimulated IL-1 and IL-6 production by rat macrophages in a dose
dependent manner in the range of 0.025-0.1 mg/ml. They were also able to
enhance IL-1 and -6 in lipopolysaccharide-stimulated macrophages. The results
suggest a strong immunostimulant action of this plant.
=============================================================
4.) Uncaria tomentosa (Willd.) DC.--ethnomedicinal use and new pharmacological,
toxicological and botanical results.
=============================================================
J Ethnopharmacol 1999 Jan;64(1):23-34 (ISSN: 0378-8741)
Keplinger K; Laus G; Wurm M; Dierich MP; Teppner H [Find other articles
with these Authors]
Immodal Pharmaka GmbH, Volders, Austria.
The medicinal system of the Ashaninka Indians in Peru is portrayed.
Three categories of medical disorders and healers are recognized. A human
is viewed to consist of a physical and a spiritual being who communicate
with each other by means of a regulating element. The significance of Uncaria
tomentosa (Willd.) DC. (Rubiaceae), locally known as una de gato, in traditional
medicine is emphasized by its exclusive use by priests to influence this
regulation. Pharmacological and toxicological results obtained with extracts
or isolated compounds are summarized. Pentacyclic oxindole alkaloids stimulate
endothelial cells in vitro to produce a lymphocyte-proliferation-regulating
factor. Tetracyclic oxindole alkaloids act as antagonists. A significant
normalization of lymphocyte percentage was observed in vivo although total
leucocyte numbers did not change.
=============================================================
5.) Induction of apoptosis and inhibition of proliferation in human
tumor cells treated with extracts of Uncaria tomentosa.
=============================================================
Anticancer Res 1998 Sep-Oct;18(5A):3363-8 (ISSN: 0250-7005)
Sheng Y; Pero RW; Amiri A; Bryngelsson C [Find other articles with these
Authors]
Department of Cell and Molecular Biology, University of Lund, Sweden.
[email protected].
Growth inhibitory activities of novel water extracts of Uncaria tomentosa
(C-Med-100) were examined in vitro using two human leukemic cell lines
(K562 and HL60) and one human EBV-transformed B lymphoma cell line (Raji).
The proliferative capacities of HL60 and Raji cells were strongly suppressed
in the presence of the C-Med-100 while K562 was more resistant to the inhibition.
Furthermore, the antiproliferative effect was confirmed using the clonogenic
assay, which showed a very close correlation between C-Med-100 concentration
and the surviving fraction. The suppressive effect of Uncaria tomentosa
extracts on tumor cell growth appears to be mediated through induction
of apoptosis which was demonstrated by characteristic morphological changes,
internucleosomal DNA fragmentation after agarose gel electrophoresis and
DNA fragmentation quantification. C-Med-100 induced a delayed type of apoptosis
becoming most dose-dependently prominent after 48 hours of exposure. Both
DNA single and double strand breaks were increased 24 hours after C-Med-100
treatment, which suggested a well-established linkage between the DNA damage
and apoptosis. The induction of DNA strand breaks coupled to apoptosis
may explain the growth inhibition of the tumor cells by Uncaria tomentosa
extracts. These results provide the first direct evidence for the antitumor
properties of Uncaria tomentosa extracts to be via a mechanism of selective
induction of apoptosis.
=============================================================
6.) Evaluation of the toxicity of Uncaria tomentosa by bioassays in
vitro.
=============================================================
J Ethnopharmacol 1997 Aug;57(3):183-7 (ISSN: 0378-8741)
Santa Maria A; Lopez A; Diaz MM; Alban J; Galan de Mera A; Vicente Orellana
JA; Pozuelo JM [Find other articles with these Authors]
Departamento de Toxicologia, Instituto de Salud Carlos III, Majadahonda,
Madrid, Spain.
Aqueous extracts of Uncaria tomentosa (Willdenow ex Roemer and Schultes)
DC. (Rubiaceae) ('Una de gato'), were analyzed for the presence of toxic
compounds in Chinese hamster ovary cells (CHO) and bacterial cells (Photobacterium
phosphoreum). Toxicity was evaluated by four systems: Neutral red assay
(NR), total protein content (KB), tetrazolium assay (MTT) and Microtox
test. The extracts of U. tomentosa did not show toxicity in vitro at the
concentrations tested. Testing in vitro could be a valuable tool for evaluating
toxicity of medicinal plants.
=============================================================
7.) Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human
endothelial cells to release a lymphocyte-proliferation-regulating factor.
=============================================================
Planta Med 1998 Dec;64(8):701-4 (ISSN: 0032-0943)
Wurm M; Kacani L; Laus G; Keplinger K; Dierich MP [Find other articles
with these Authors]
Institut fur Hygiene, Leopold-Franzens-Universitat Innsbruck, Austria.
In the present study we show that pentacyclic but not tetracyclic oxindole
alkaloids from Uncoria tomentosa (Willd.) DC. (Rubiaceae) induced EA.hy926
endothelial cells to release some yet to be determined factor(s) into the
supernatant; this factor was shown to significantly enhance proliferation
of normal human resting or weakly activated B and T lymphocytes. In contrast,
proliferation of normal human lymphoblasts and of both the human lymphoblastoid
B cell line Raji and the human lymphoblastoid T cell line Jurkat was inhibited
significantly while cell viability was not affected. Tetracyclic oxindole
alkaloids dose-dependently reduce the activity of pentacyclic oxindole
alkaloids on human endothelial cells.
=============================================================
8.) Depletion of specific binding sites for estrogen receptor by Uncaria
tomentosa.
=============================================================
Proc West Pharmacol Soc 1998;41:123-4 (ISSN: 0083-8969)
Salazar EL; Jayme V [Find other articles with these Authors]
Unidad de Investigacion Medica en Biologia de la Reproduccion, Hospital
de Gineco Obstetricia Luis Castelazo Ayala IMSS, Mexico, D.F.
=============================================================
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9.) Antiinflammatory actions of cat's claw: the role of NF-kappaB.
=============================================================
Aliment Pharmacol Ther 1998 Dec;12(12):1279-89 (ISSN: 0269-2813)
Sandoval-Chacon M; Thompson JH; Zhang XJ; Liu X; Mannick EE; Sadowska-Krowicka
H; Charbonnet RM; Clark DA; Miller MJ [Find other articles with these Authors]
LSU Medical Center, Department of Paediatrics and Stanley S. Scott
Cancer Center, New Orleans, LA 70112, USA.
BACKGROUND: Uncaria tomentosa is a vine commonly known as cat's claw
or 'una de gato' (UG) and is used in traditional Peruvian medicine for
the treatment of a wide range of health problems, particularly digestive
complaints and arthritis. PURPOSE: The aim of this study was to determine
the proposed anti-inflammatory properties of cat's claw. Specifically:
(i) does a bark extract of cat's claw protect against oxidant-induced stress
in vitro, and (ii) to determine if UG modifies transcriptionally regulated
events. METHODS: Cell death was determined in two cell lines, RAW 264.7
and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression
of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects
on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in
RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation
was induced in rats with indomethacin (7.5 mg/kg), with UG administered
orally in the drinking water (5 mg/mL). RESULTS: The administration of
UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis
in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat's claw inhibited
lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell
death and inhibited the activation of NF-kappaB. Cat's claw markedly attenuated
indomethacin-enteritis as evident by reduced myeloperoxidase activity,
morphometric damage and liver metallothionein expression. CONCLUSIONS:
Cat's claw protects cells against oxidative stress and negated the activation
of NF-kappaB. These studies provide a mechanistic evidence for the widely
held belief that cat's claw is an effective anti-inflammatory agent.
=============================================================
10.) Mutagenic and antimutagenic activities of Uncaria tomentosa and
its extracts.
=============================================================
J Ethnopharmacol 1993 Jan;38(1):63-77
Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L, Stivala
LA
Departmento di Farmacologia, Chemioterapia e Tossicologia Medica, Universita
degli Studi di Milano, Italy.
Mutagenic and antimutagenic activities of extracts and chromatographic
fractions of Uncaria tomentosa bark are reported. The plant extracts and
fractions show no mutagenic effect in different strains of Salmonella typhimurium
with and without metabolic activation. However, the plant extracts and
fractions show a protective antimutagenic effect in vitro against photomutagenesis
induced by 8-methoxy-psoralen (8-MOP) plus UVA in S. typhimurium TA 102.
A decoction of U. tomentosa ingested daily for 15 days by a smoker decreased
the mutagenicity induced in S. typhimurium TA98 and TA100 by the subject's
urine.
=============================================================
11.) Plant metabolites. New compounds and anti-inflammatory activity
of Uncaria tomentosa.
=============================================================
J Nat Prod 1991 Mar-Apr;54(2):453-9
Aquino R, De Feo V, De Simone F, Pizza C, Cirino G
Dipartimento di Chimica delle Sostanze Naturali, Universita degli Studi
di Napoli Federico II, Italy.
Bioassay-directed fractionation of the anti-inflammatory extracts of
Uncaria tomentosa, using the carrageenan-induced edema in rat paw, has
led to the isolation of a new quinovic acid glycoside 7 as one of the active
principles. Furthermore, a new triterpene 8 was isolated as its methyl
ester. The structures were elucidated by spectral and chemical studies.
=============================================================
12.) New polyhydroxylated triterpenes from Uncaria tomentosa.
=============================================================
J Nat Prod 1990 May-Jun;53(3):559-64
Aquino R, De Simone F, Vincieri FF, Pizza C, Gacs-Baitz E
Dipartimento di Chimica delle Sostanze Naturali, Universita degli Studi
di Napoli, Italy.
Three novel polyhydroxylated triterpenes have been isolated from Uncaria
tomentosa. Their structures were established as 1, 2, and 3 by detailed
spectral studies including 1H-13C correlations via long range couplings
using the INAPT pulse sequence, nOeds, and 2D 1H-13C direct chemical shift
correlation (HETCOR) nmr techniques.
=============================================================
13.) Plant metabolites. Structure and in vitro antiviral activity of
quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda.
=============================================================
J Nat Prod 1989 Jul-Aug;52(4):679-85
Aquino R, De Simone F, Pizza C, Conti C, Stein ML
Dipartimento di Chimica delle Sostanze Naturali, Universita di Napoli,
Italy.
A reinvestigation of the bark of Uncaria tomentosa afforded, in addition
to the major quinovic acid glycosides 1-3, three further glycosides 4-6.
The structures were elucidated by spectral and chemical studies. Furthermore,
a series of antiviral tests were performed on all these glycosides and
on the related glycosides 7-9, previously isolated from Guettarda platypoda.
=============================================================
14.) [Phytochemical and biological study of Uncaria tomentosa].
=============================================================
Boll Soc Ital Biol Sper 1989 Jun;65(6):517-20
Senatore A, Cataldo A, Iaccarino FP, Elberti MG
The investigation on steroidic fraction of Uncaria tomentosa, commonly
called Una de gato, showed the presence of beta-sitosterol (60%), stigmasterol,
and campesterol. The percentage of sterols have been carried out by GLC.
The spectroscopic data 1H-NMR and MS of the three compounds are also reported,
with the beta-sitosterol as the main sterol. Preliminary pharmacological
investigations prove a moderate antiinflammatory activity.
=============================================================
15.) The alkaloids of Uncaria tomentosa and their phagocytosis-stimulating
action].
Planta Med 1985 Oct;(5):419-23
=============================================================
=============================================================
16.) CAT'S CLAW (Una de Gato) #K725 INGREDIENTS:
=============================================================
Each VEGICAP®: Capsule Contains: 500 Mg. of Cat's Claw (Una de
Gato), (Uncaria Tomentosa Standardized 4:1 Extract)
This concentrated herbal extract contains no sugar, yeast, corn, wheat,
rice, soy, artificial color, flavor or preservatives. Contains NO animal
products. VEGICAPS®: is a registered trademark of GS Technologies.
PHYSIOLOGY:
------------
After using cat's claw in working with approximatly 150 patients between
1988 and 1992, Dr. Brent Davis reports that Uncaria Tomentosa has the ability
to break through severe intestinal derangements that no other available
products can touch. He refers to the herb as "the opener of the way" because
of its remarkable ability to cleanse the entire intestinal tract and help
patients suffering from many different stomach and bowel disorders. A wealth
of beneficial phytochemicals have been found in cat's claw including quinovic
acid glycosides, several oxindol alkaloids, proanthocyanidins, polyphenols,
triterpines and the plant sterols beta-siosterol, stigmasterol and campesterol.
Rynchophylline a fifth alkaloid found in cat's claw displays an ability
to inhibit platelet aggregation and thrombosis. This suggests that cat's
claw be be useful in preventing strokes and reducing the risk of heart
attack by lowering blood pressure, increasing circulation, inhibiting formation
of plaque on arterial walls and formation of blood clots in the brain,
heart and arteries.
INDICATIONS:
-------------
May be useful as an anti-inflammatory, arthritis, rheumatism, bursitis
and gout, immune deficiencies, intestinal permeability and toxic overload.
=============================================================
CARTILAGO DE TIBURON / SHARK CARTILAGE
=============================================================
=============================================================
17.) How useful are unconventional cancer treatments?
=============================================================
Eur J Cancer 1999 Oct;35(11):1608-13
Ernst E, Cassileth BR
Department of Complementary Medicine, School of Postgraduate Medicine
and Health Sciences, University of Exeter, U.K. [email protected]
Unconventional cancer treatments are used frequently. Therefore, oncologists
need to know about them. This article gives an overview of current knowledge
on the most prevalent complementary or alternative cancer therapies. A
distinction is made between alleged cures, preventive and adjunctive measures.
Shark cartilage, mistletoe, thymus therapy, essiac, hydrazine sulphate,
714-X, dietary regimens, green tea and Panax ginseng are all covered specifically.
None of these treatments offer reasonable hope for a cure. Some strategies
are promising in terms of cancer prevention. The true potential of unconventional
therapies might lie in adjunctive and palliative care. It is concluded
that good evidence in this area is scarce. Vis-a-vis the high prevalence
of unconventional cancer treatments, rigorous investigations are mandatory,
not least for increasing the safety of future patients.
=============================================================
18.) A monoclonal antibody which recognizes a glycosaminoglycan epitope
in both dermatan sulfate and chondroitin sulfate proteoglycans of human
skin.
=============================================================
Histochem J 1999 Aug;31(8):549-58
Sorrell JM, Carrino DA, Baber MA, Asselineau D, Caplan AI
Department of Biology and Skeletal Research Center, Case Western Reserve
University, Cleveland, OH 44106, USA.
Studies have been initiated to identify various cell surface and matrix
components of normal human skin through the production and characterization
of murine monoclonal antibodies. One such antibody, termed PG-4, identifies
both cell surface and matrix antigens in extracts of human foetal and adult
skin as the dermatan sulfate proteoglycans, decorin and biglycan, and the
chondroitin sulfate proteoglycan versican. Treatment of proteoglycans with
chondroitinases completely abolishes immunoreactivity for all of these
antigens which suggests that the epitope resides within their glycosaminoglycan
chains. Further evidence for the carbohydrate nature of the epitope derives
from competition studies where protein-free chondroitin sulfate chains
from shark cartilage react strongly; however, chondroitin sulfate chains
from bovine tracheal cartilage fail to exhibit a significant reactivity,
an indication that the epitope, although present in some chondroitin sulfate
chains, does not consist of random chondroitin 4- or 6-sulfate disaccharides.
The presence of the epitope on dermatan sulfate chains and on decorin was
also demonstrated using competition assays. Thus, PG-4 belongs to a class
of antibodies that recognize native epitopes located within glycosaminoglycan
chains. It differs from previously described antibodies in this class in
that it identifies both chondroitin sulfate and dermatan sulfate proteoglycans.
These characteristics make PG-4 a useful monoclonal antibody probe to identify
the total population of proteoglycans in human skin.
=============================================================
19.) [The national cancer fund (Koningin Wilhelmina Fonds) and the
Houtsmuller-therapy for cancer].
=============================================================
Ned Tijdschr Geneeskd 1999 Jul 3;143(27):1431-3
Renckens CN, van Dam FS
Nederlands Kanker Instituut/Antoni van Leeuwenhoek ziekenhuis, afd.
Psychosociaal Onderzoek en Epidemiologie, Amsterdam.
Dr. Houtsmuller, a retired internist, introduced an anticancer diet
ten years ago. He claimed to have cured himself from metastatic melanoma
by following a diet consisting of healthy nutrients, large amounts of vitamins,
minerals, antioxidants and shark cartilage powder in combination with psychological
support. The efficacy of the therapy was never described in a scientific
article. Currently about 63% of all cancer patients in the Netherlands
using a diet use the Houtsmuller diet. The national cancer fund (Koningin
Wilhelmina Fonds) invited him to speak at their 50-year commemorative symposium.
Shortly before he admitted that his medical history did not mention metastatic
melanoma. Dr. Houtsmuller has seriously damaged the position of physicians
in the Netherlands by addressing patients directly without first seeking
support from his scientific medical peers. Cancer organizations such as
Koningin Wilhelmina Fonds are urged to properly inform the public about
the real value or lack of value of alternative treatments in general and
of alternative diets in particular.
=============================================================
20.) Effect of U-995, a potent shark cartilage-derived angiogenesis
inhibitor, on anti-angiogenesis and anti-tumor activities.
=============================================================
Anticancer Res 1998 Nov-Dec;18(6A):4435-41
Sheu JR, Fu CC, Tsai ML, Chung WJ
Cancer Research Center, Gwo-Chyang GMP Pharmaceutical Co., Ltd., Tainan,
Taiwan. [email protected]
BACKGROUND: A potent angiogenesis inhibitor, U-995, has been purified
from the cartilage of the blue shark (Prionace glauca). U-995 is composed
of two single peptides with molecular mass of 10 and 14 kDa, respectively.
MATERIALS AND METHODS: U-995 was designed to study human umbilical vein
endothelial cell (HUVEC) migration and proliferation in vitro and angiogenesis
induced by TNF alpha in chicken chorioallantoic membrane (CAM). Furthermore,
we determined the ability of U-995 to inhibiting tumor cell growth and
metastasis. RESULTS: U-995 (15 and 30 micrograms/ml) markedly inhibited
HUVEC migration and, at 15-50 micrograms/ml produced a dose-dependent decline
in [3H]-thymidine incorporation. 30 and 50 micrograms/ml of U-995, when
added to TNF alpha-induced angiogenesis caused discontinuous and disrupted
blood vessels. Moreover, U-995 (30 micrograms/ml) markedly prevented collagenase-induced
collagenolysis. In addition, when 200 micrograms U-995 was injected i.p.
into mice it suppressed sarcoma-180 cell growth and B16-F10 mouse melanoma
cell metastasis in vivo. CONCLUSIONS: These results suggest that the anti-angiogenic
effects of U-995 may be be due to interference with the proliferation and
migration of HUVECs as well as inhibition of collagenolysis, thereby leading
to inhibition of both angiogenesis and tumor cell growth.
=============================================================
21.) Shark cartilage-containing preparation: protection against reactive
oxygen species.
=============================================================
Food Chem Toxicol 1998 Dec;36(12):1079-84
Felzenszwalb I, Pelielo de Mattos JC, Bernardo-Filho M, Caldeira-de-Araujo
A
Universidade do Estado do, Rio de Janeiro, Instituto de Biologia, Departamento
de Biofisica e Biometria, Brazil.
There is overwhelming evidence to indicate that free radicals cause
oxidative damage to lipids, proteins and nucleic acids and are involved
in the pathogenesis of several degenerative diseases. Therefore, antioxidants,
which can neutralize free radicals, may be of central importance in the
prevention of these disease states. The protection that fruits and vegetables
provide against disease has been attributed to the various antioxidants
contained in them. Recently, an anti-inflammatory and analgesic activity
of a water-soluble fraction from shark cartilage has been described. Using
electrophoretical assays, bacteria survival and transformation and the
Salmonella/mammalian-microsome assay, we investigated the putative role
of shark cartilage-containing preparation in protecting cells against reactive
oxygen species induced DNA damage and mutagenesis. If antimutagens are
to have any impact on human disease, it is essential that they are specifically
directed against the most common mutagens in daily life. Our data suggest
that shark cartilage-containing preparation can play a scavenger role for
reactive oxygen species and protects cells against inactivation and mutagenesis.
=============================================================
22.) The effect of shark cartilage extracts on the growth and metastatic
spread of the SCCVII carcinoma.
=============================================================
Acta Oncol 1998;37(5):441-5
Horsman MR, Alsner J, Overgaard J
Danish Cancer Society, Department of Experimental Clinical Oncology,
Aarhus University Hospital.
This study was designed to investigate the potential of shark cartilage
extracts to inhibit the growth and metastatic spread of a murine solid
tumour. The SCCVII carcinoma, implanted in the right rear foot of C3H mice,
was used. Following tumour implantation, two different commercially available
extracts of shark cartilage (Sharkilage and MIA Shark Powder) were dissolved
in water and orally administered to the mice at doses that ranged from
5 to 100 mg per mouse. These injections were repeated on a daily basis
for up to 25 days post-implantation of the primary tumour. Compared to
non-drug-treated animals, daily administration of the shark cartilage extracts
did not show any adverse toxicity (as measured by changes in body weight
and lethality). More importantly, none of the shark cartilage doses tested
had any retarding effect on the growth of the primary tumour, nor did they
inhibit the development of metastases seen in the lungs of the tumour-bearing
mice at autopsy. In conclusion, our results offer no support for the proposed
use of shark cartilage extracts as an anti-cancer therapy.
=============================================================
23.) Phase I/II trial of the safety and efficacy of shark cartilage
in the treatment of advanced cancer.
=============================================================
J Clin Oncol 1998 Nov;16(11):3649-55
Miller DR, Anderson GT, Stark JJ, Granick JL, Richardson D
Cancer Treatment Research Foundation, Cancer Treatment Centers of America,
Arlington Heights, IL 60005, USA. [email protected]
PURPOSE: Patients with cancer and chronic inflammatory disorders have
used shark cartilage (SC) preparations for many years. Preclinical studies
that support their beneficial effects are scanty, and reports of clinical
trials have been anecdotal. The proposed mechanisms of antitumor action
include direct or indirect inhibition of angiogenesis. Because of the emerging
use of SC as an alternative to conventional cancer therapy, this trial
was launched to evaluate the safety and efficacy of SC. PATIENTS AND METHODS:
Sixty adult patients with advanced previously treated cancer (breast, 16
patients; colorectal, 16 patients; lung, 14 patients; prostate, eight patients;
non-Hodgkin lymphoma, three patients; brain, one patient; and unknown primary
tumor, two patients) were enrolled. Eligibility criteria included confirmation
of diagnosis, resistance to conventional therapy, objective measurable
disease, life expectancy of 12 weeks or greater, Eastern Cooperative Oncology
Group (ECOG) performance status of 0 to 2, no recent or concomitant anticancer
therapy, no prior SC, and informed consent. Patients underwent evaluation
of the extent of disease, quality-of-life score (Functional Assessment
of Cancer Therapy-General [FACT-G] scale), and hematologic, biochemical,
and selected immune function studies at baseline and after 6 and 12 weeks
of SC therapy. The dose of SC was 1 g/kg daily orally in three divided
doses. Standard criteria were used to evaluate adverse events and response.
RESULTS: Ten of 60 patients were lost to follow-up(LTFU) or refused further
treatment (RFT) before the 6-week evaluation and were not assessable for
toxicity and response. Three patients with stable disease at 6 weeks were
LTFU or RFT thereafter. Of the 47 fully assessable patients, five were
taken off study because of gastrointestinal toxicity or intolerance to
SC. Progressive disease (PD) at 6 or 12 weeks occurred in 22 and five patients,
respectively. Five patients died of PD while undergoing SC therapy. No
complete (CRs) or partial responses (PRs) were noted. Median time to tumor
progression in the entire study population was 7+/-9.7 weeks (mean, 11.4
weeks; range, 3.7 to 45.7 weeks). Ten (20%) of 50 assessable patients,
or 16.7% of the 60 intent-to-treat patients, had stable disease (SD) for
12 weeks or more. The median time to tumor progression was 27 weeks, the
mean was 28.8+/-9.9 weeks, and the range was 18.6 to 45.7 weeks. In this
subset, FACT-G scores improved in four patients, were unchanged in four
patients, and declined in two patients. Twenty-one adverse events (grade
1, eight events; grade 2, seven events; and grade 3, six events) were recorded,
14 of which were gastroenterologic (nausea, vomiting, constipation). CONCLUSION:
Under the specific conditions of this study, SC as a single agent was inactive
in patients with advanced-stage cancer and had no salutary effect on quality
of life. The 16.7% rate of SD was similar to results in patients with advanced
cancer treated with supportive care alone.
=============================================================
24.) Occurrence of a novel collagen with three distinct chains in the
cranial cartilage of the squid Sepia officinalis: comparison with shark
cartilage collagen.
=============================================================
Biochim Biophys Acta 1998 Jul 23;1381(2):161-9
Sivakumar P, Chandrakasan G
Department of Biochemistry, Central Leather Research Institute, Adyar,
Chennai 600 020, India.
A unique collagen with three distinct chains, was purified from the
cranial cartilage of the squid Sepia officinalis, by pepsinisation and
salt precipitation and compared with shark cartilage collagen. These chains,
which were different from the known cartilage collagen chains, were referred
as C1, C2 and C3, had approximate molecular weights of 105 kDa, 115 kDa
and 130 kDa, respectively, and were present in a ratio of 3:2:1, suggestive
of two molecules of composition, [(C1)2C2] and [C1C2C3]. These collagens
were purified by fractionation at acid and neutral pH, and by ammonium
sulfate precipitation. Solubility data indicated that this collagen was
more crosslinked than the type I collagen isolated from cartilage of shark,
Carcharius acutus. In vitro fibrillogenesis revealed that the sepia collagen
formed denser aggregates, as compared to shark collagen, and was stabilised
by a higher degree of carbohydrate association. Polyclonal antisera raised
against shark collagen was also reactive against the sepia collagens, while
the converse was not true, indicating the high immunospecificity of the
latter. These results demonstrate collagen polymorphism in an invertebrate
cartilage and may hold significance in understanding tissue calcification
and molecular evolution. Further, these collagens may represent ancestral
forms of vertebrate minor collagens like typeV/XI. Copyright 1998 Elsevier
Science B.V. All rights reserved.
=============================================================
25.) Antiangiogenic properties of a novel shark cartilage extract:
potential role in the treatment of psoriasis.
=============================================================
J Cutan Med Surg 1998 Jan;2(3):146-52
Dupont E, Savard PE, Jourdain C, Juneau C, Thibodeau A, Ross N, Marenus
K, Maes DH, Pelletier G, Sauder DN
Les Laboratoires Aeterna, Ste-Foy, PQ, Canada.
BACKGROUND: A number of inflammatory and immune diseases are associated
with vascular changes. Psoriasis, as an example, is a common inflammatory
skin disease with dilation of capillaries as an early histological change.
In more developed psoriatic lesions there is proliferation of blood vessels
and neovascularization. The use of agents that target these vascular changes
represents a novel therapeutic strategy in the treatment of inflammatory
diseases. Since cartilage is an avascular tissue, it has been hypothesized
that there may be factors found in cartilage that inhibit blood vessel
formation. OBJECTIVE: The objectives of this study were 1) to determine
whether extracts of cartilage could inhibit angiogenesis, and 2) since
altered angiogenesis is associated with certain diseases, including psoriasis,
to examine whether inhibition of angiogenesis could potentially contribute
to the treatment of psoriasis. METHODS: Extracts of shark cartilage were
prepared by homogenization and ultrafiltration to derive the active agent
termed AE -941. This agent was tested for antiangiogenesis activity using
the embryonic vascularization test, which is a modification of the ex vivo
chick embryo culture (CAM). Since one of the first steps in angiogenesis
is degradation by metalloproteinases of the basement membrane of capillaries,
AE -941 was tested for collagenase activity using a fluorogenic peptide
substrate. Anti-inflammatory properties were tested using a cutaneous irritation
model in humans. RESULTS: A dose dependent inhibition in embryonic neovascularization
as well as in collagenase activity by AE -941 was demonstrated. When test
compounds were applied on the forearms of test subjects, AE -941 was shown
to have anti-inflammatory properties. Anecdotal data suggested that topical
AE -941 had a beneficial effect in psoriasis. CONCLUSION: Our results show
that AE -941 has anti-angiogenic and anti-inflammatory properties. Antiangiogenesis
agents such as AE -941 provide an entirely new class of agents to treat
cutaneous and systemic diseases associated with altered vascularity.
=============================================================
26.) Dietary supplement use by women at risk for breast cancer recurrence.
The Women's Healthy Eating and Living Study Group.
=============================================================
J Am Diet Assoc 1998 Mar;98(3):285-92
Newman V, Rock CL, Faerber S, Flatt SW, Wright FA, Pierce JP
Department of Family and Preventive Medicine, University of California-San
Diego, La Jolla 92093-0901, USA.
OBJECTIVE: To develop a method of collecting, organizing, and analyzing
information on nutrient and nonnutrient dietary supplement use by women
at risk for breast cancer recurrence as a component of nutrition assessment
and monitoring, and to describe the characteristics associated with dietary
supplement use in this population at enrollment in a clinical trial to
prevent breast cancer recurrence. DESIGN: Cross-sectional descriptive study
design. SUBJECTS: Women diagnosed with breast cancer within the previous
4 years (n=435). ANALYSIS: Dietary supplements reported in four 24-hour
dietary recalls were categorized according to primary nutrient and nonnutrient
contents. Prevalence of dietary supplement use is described. Associations
between supplement use and demographic and participant characteristics
were examined using chi(2) analysis and logistic regression. RESULTS: Dietary
supplement use was reported by 80.9% of the women. Increased likelihood
of supplement use was associated with demographic (eg, older age, higher
level of education, white race vs other ethnic groups) and personal (eg,
lower body mass index, moderate alcohol consumption) characteristics. Use
of vitamin C and related compounds, other nutrients (eg, n-3 fatty acids,
evening primrose oil), and herbal products was inversely associated with
months since diagnosis; use of miscellaneous supplements (eg, shark cartilage)
was directly associated with more advanced stage at diagnosis. APPLICATIONS:
Monitoring dietary supplement use is an important aspect of nutrition assessment,
especially in populations with chronic health conditions or medical diagnoses.
Demographic and personal characteristics, time passed since diagnosis,
and stage of cancer at diagnosis are predictive of dietary supplement use
by women at risk for breast cancer recurrence. Associations in this population
may be present in other groups that are the object of nutrition intervention
efforts.
=============================================================
27.) The analgesic and anti-inflammatory effects of shark cartilage
are due to a peptide molecule and are nitric oxide (NO) system dependent.
=============================================================
Biol Pharm Bull 1997 Nov;20(11):1151-4
Fontenele JB, Araujo GB, de Alencar JW, Viana GS
Department of Physiology and Pharmacology, Federal University of Ceara,
Fortaleza, CE, Brazil.
The present work shows an antinociceptive and dose-dependent effect
of shark cartilage hydrosoluble fraction (HF) on writhing and formalin
tests in mice. The effect was not altered by thalidomide, a known inhibitor
of tumor necrosis factor-alfa (TNF-alfa) synthesis. Similarly, the antinociceptive
effect did not change in the presence of naloxone, indicating that the
opioid system is not involved. However, the effect observed was blocked
by L-arginine, a NO synthesis substrate, and it was potentiated by L-NAME,
suggesting a role of the NO system in the shark cartilage antinociceptive
effect. Effects similar to those seen with the HF were detected with peak
II from gel filtration chromatography. The increase in vascular permeability
induced by serotonin in rats was significantly abolished by the HF at the
dose of 2 mg/kg, p.o., and again it was not potentiated by thalidomide.
The observed blockade in the vascular permeability increase induced by
histamine was detected only with a higher dose (10 mg/kg, p.o.).
=============================================================
28.) Shark cartilage-induced hepatitis.
=============================================================
Ann Intern Med 1996 Nov 1;125(9):780-1
Ashar B, Vargo E
Publication Types:
Letter
=============================================================
=============================================================
29.) Anti-inflammatory and analgesic activity of a water-soluble fraction
from shark cartilage.
=============================================================
Braz J Med Biol Res 1996 May;29(5):643-6
Fontenele JB, Viana GS, Xavier-Filho J, de-Alencar JW
Departamento de Fisiologia e Farmacologia, Universidade Federal do
Ceara, Fortaleza, CE, Brasil.
The anti-inflammatory and analgesic activities of a water-soluble fraction
(WSF), extracted with 0.1 M ammonium bicarbonate, pH 8.0, from shark cartilage
were studied in several experimental models. Orally administered WSF (10
mg/kg) caused 25.7 and 23.6% inhibition of the paw edema produced in female
Wistar rats (200-250 g) by carrageenan and dextran, respectively, after
3 h, as compared to controls. WSF administered orally had no effect on
acetic acid-induced writhings in male Swiss mice (25-30 g) at the dose
of 0.01 mg/kg but caused 52.8 and 61.4% inhibition at the doses of 0.1
and 0.5 mg/kg, respectively, compared to controls (No. of writhings/20
min, means +/- SEM: treated groups = 18.6 +/- 2.5, N = 12 and 15.2 +/-
1.4, N = 12, respectively; controls = 39.3 +/- 1.3, N = 77). In the formalin
test (male Swiss mice, 25-30 g), orally administered WSF (0.5 and 1 mg/kg)
caused 12.0 and 46.6% inhibition of licking time, respectively, only in
the 2nd phase (inflammatory) of the test (licking time, means +/- SEM:
treated group = 18.3 +/- 4.4 sec, N = 7 and 11.1 +/- 3.4 sec, N = 13; controls
= 20.8 +/- 2.4 sec, N = 44). The results suggest that a molecule of a protein
nature in shark cartilage is probably responsible for the effects observed.
=============================================================
30.) Shark-cartilage containing preparation protects cells against
hydrogen peroxide induced damage and mutagenesis.
=============================================================
Mutat Res 1996 Apr 6;367(4):204-8
Gomes EM, Souto PR, Felzenszwalb I
CETOX-Departamento de Biofisica e Biometria, Universidade do Estado
do Rio de Janeiro, Brazil.
Natural products from flora and fauna are frequently used as nutritional
supplements and medicaments. Two short-term assays were carried out and
negative results were obtained for shark-cartilage containing preparation.
The tests employed were the Salmonella/mammalian microsome assay using
tester strains TA97, TA98, TA100, TA102 and TA1535 with or without S9 mix
and the SOS-Chromotest with Escherichia coli strain PQ37. Evidence for
shark-cartilage containing preparation functioning as an antimutagen was
detected. Using bacterial survival assays with Escherichia coli fpg (BH20)
and xthA (BW9091), we investigated the putative role of shark-cartilage
containing preparation in protecting cells against lesions induced by hydrogen
peroxide in normal and low iron level conditions. Our data suggest that
shark-cartilage containing preparation can play a scavenger role for reactive
oxygen species and protect against DNA lesions in both conditions.
Antiproliferative activity of shark cartilage with and without tumor
necrosis factor-alpha in human umbilical vein endothelium.
Pharmacotherapy 1996 Mar-Apr;16(2):237-44
=============================================================
31.) McGuire TR, Kazakoff PW, Hoie EB, Fienhold MA
Department of Pharmacy Practice, University of Nebraska, =============================================================
Omaha 68198-6045, USA.
We evaluated the antiangiogenic activity of shark cartilage, tumor necrosis
factor-alpha (TNF-alpha), and a combination of the two using a human umbilical
vein endothelial cell proliferation assay. Proliferation of endothelium
is a hallmark of angiogenesis, and inhibition of endothelial cell proliferation
indicates potential antiangiogenic activity. Shark cartilage produced a
concentration-dependent decline in endothelial cell 3H-thymidine incorporation.
This activity was heat stable and was found in molecular weight fractions
of less than 10 kd. The antiproliferative effect of shark cartilage was
specific for vascular endothelium and did not affect the proliferative
rate of human astrocytoma cells or human skin fibroblasts. Shark cartilage
at a concentration of 500 mu g/ml and TNF-alpha at a concentration of 10
ng/ml reduced endothelial cell proliferation by 32% and 29%, respectively.
Treatment of endothelial cells with the combination of shark cartilage
and TNF-alpha resulted in a 44% reduction in endothelial cell proliferation.
The isolation and identification of the active components of shark cartilage
is continuing.
=============================================================
32.) Demonstration of immunogenic keratan sulphate in commercial chondroitin
6-sulphate from shark cartilage. Implications for ELISA assays.
=============================================================
Clin Chim Acta 1995 May 15;236(2):195-204
Moller HJ, Moller-Pedersen T, Damsgaard TE, Poulsen JH
Department of Clinical Biochemistry, K.H. University Hospital, Aarhus,
Denmark.
The prototype monoclonal keratan sulphate (KS) antibody 5D4 that is
widely used for detection of KS in tissues and biological fluids reacts
strongly with commercial low grade shark cartilage chondroitin 6-sulphate.
Characterization of the immunogenic material by chondroitinase ABC digestion,
ELISA inhibition studies, immunoblotting and HPLC analyses confirmed the
presence of substantial amounts of KS, probably as a large proteoglycan
(> 120 kDa). Commercial and heterogenic glycosaminoglycan preparations
therefore must be used with great caution in immunological analyses. On
the other hand the shark cartilage chondroitin 6-sulphate is an easy accessible
source of immunogenic KS that can be used as a reference standard and as
coating antigen in KS-ELISAs. The concentration of immunogenic KS in synovial
fluid measured with an ELISA based solely on reagents of shark cartilage
chondroitin 6-sulphate correlated well (r = 0.90) with the concentrations
obtained with a traditional KS-ELISA that uses purified aggrecan as standard
and coating antigen, and KS in both serum and synovial fluid could be measured
with sufficient linearity.
=============================================================
33.) Production and characterization of monoclonal antibodies to shark
cartilage proteoglycan.
=============================================================
Braz J Med Biol Res 1994 Sep;27(9):2103-8
Alves ML, Straus AH, Takahashi HK, Michelacci YM
Departamento de Bioquimica, Escola Paulista de Medicina, Sao Paulo,
Brasil.
1. Two proteoglycans, PG1 and PG2, have been isolated from shark cartilage.
Both are highly polydisperse and large (molecular mass: 1-10 x 10(6) Daltons)
and contain chondroitin sulfate and keratan sulfate side chains, but PG2
is somewhat smaller than PG1 and contains less keratan sulfate. 2. Monoclonal
antibodies were raised against PG1. Many antibodies were obtained and one
of them, MST1, was subcloned and further characterized. This monoclonal
antibody reacts with PG1 and PG2 from shark cartilage and also with aggrecan
from bovine trachea cartilage. Chondroitinase AC-treated proteoglycans
react with MST1, indicating that the antibody does not recognize chondroitin
sulfate. MST1 also recognizes aggrecan from human cartilage and a proteoglycan
from bovine brain (neurocan) but it does not recognize proteoglycans from
rat Walker tumor, fetal calf muscle and decorin from human myoma. 3. Using
MST1 we were able to demonstrate that both PG1 and PG2 aggregate with hyaluronic
acid.
=============================================================
34.) Differential effects of glycosaminoglycans on neurite outgrowth
from hippocampal and thalamic neurones.
=============================================================
J Cell Sci 1994 Jun;107 ( Pt 6):1437-48
Fernaud-Espinosa I, Nieto-Sampedro M, Bovolenta P
Instituto Cajal, Madrid, Spain.
Chondroitin sulphate proteoglycans are expressed in a temporally restricted
pattern from embryonic day 17 to postnatal day 0 in both the thalamus and
the cortical subplate, to which thalamic neurones transiently project.
To study whether chondroitin sulphate proteoglycans could be specifically
involved in the modulation of thalamic axon outgrowth, we compared neurite
outgrowth from cultured rat embryonic hippocampal and thalamic neurones,
in the presence of chondroitin sulphate type C (isolated from shark cartilage)
and chondroitin sulphate type B (dermatan sulphate; isolated from bovine
mucosa). When added to the culture medium, both types of glycosaminoglycan
lowered the adhesion to laminin and polylysine of both hippocampal and
thalamic neurones. However, only chondroitin sulphate specifically modified
the pattern of thalamic but not hippocampal neurone outgrowth, promoting
axon growth. The morphological changes induced by chondroitin sulphate
were concentration dependent and correlated with the selective binding
of chondroitin sulphate to the neuronal plasma membrane and its subsequent
internalisation. Chondroitin sulphate loosely bound to the surface of hippocampal
neurones, but was not internalised. These results indicate that proteoglycans,
and in particular the glycosaminoglycan component of these molecules, can
differentially modulate neurite outgrowth, depending on their biochemical
composition and on the type of neurones they bind to; this would be a possible
mechanism of controlling axon guidance in vivo.
=============================================================
35.) Structural studies on sulfated oligosaccharides derived from the
carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans
of shark cartilage. II. Seven compounds containing 2 or 3 sulfate residues.
=============================================================
J Biol Chem 1992 Mar 25;267(9):6036-43
de Waard P, Vliegenthart JF, Harada T, Sugahara K
Department of Bio-Organic Chemistry, Utrecht University, The Netherlands.
Shark cartilage proteoglycans bear predominantly chondroitin 6-sulfate.
After exhaustive protease digestion, reductive beta-elimination and subsequent
chondroitinase ABC digestion, 13 hexasaccharide alditols were obtained
from the carbohydrate-protein linkage region and six of them contain 0
or 1 sulfate and/or 1 phosphate residue (Sugahara, K., Ohi, Y., Harada,
T., de Waard, P., and Vliegenthart, J. F. G. (1992) J. Biol. Chem. 267,
6027-6035). The other seven compounds, which represent approximately 60%
of the isolated linkage hexasaccharides, were analyzed by chondroitinase
ACII digestion in conjunction with high performance liquid chromatography
and by 500-MHz one- and two dimensional 1H NMR spectroscopy. All seven
compounds have the following conventional structure in common. [formula:
see text] Two disulfated compounds have an O-sulfate on C-6 of the Gal-2
residue attached to xylitol in combination with an O-sulfate on C-4 or
on C-6 of the GalNAc residue. The third disulfated compound has O-sulfate
on C-6 of Gal-2, and also on C-6 of Gal-3. Two of the trisulfated compounds
also have O-sulfate on C-6 of both Gal-2 and Gal-3 with in addition sulfate
on C-6 or C-4 of GalNAc. The other two trisulfated compounds have O-sulfate
on C-6 of Gal-2 and on C-4 of Gal-3 in conjunction with sulfate on C-6
or C-4 of GalNAc.
=============================================================
36.) Structural studies on sulfated oligosaccharides derived from the
carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans
of shark cartilage. I. Six compounds containing 0 or 1 sulfate and/or phosphate
residues.
=============================================================
J Biol Chem 1992 Mar 25;267(9):6027-35
Sugahara K, Ohi Y, Harada T, de Waard P, Vliegenthart JF
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences,
Kyoto University, Japan.
Shark cartilage proteoglycans bear predominantly chondroitin 6-sulfate.
After exhaustive protease digestion, reductive beta-elimination, and subsequent
chondroitinase ABC digestion, 13 hexasaccharide alditols, which are nonsulfated,
sulfated, and/or phosphorylated, were obtained from the carbohydrate-protein
linkage region. Six compounds, containing 0 or 1 sulfate and/or phosphate
residue, represent approximately 40% of the isolated linkage hexasaccharide
alditols. They were analyzed by chondroitinase ACII or alkaline phosphatase
digestion in conjunction with high performance liquid chromatography, and
by 500 MHz one- and two-dimensional 1H NMR spectroscopy. All six compounds
have the conventional structure in common. Delta 4,5-GlcA beta 1-3GalNAc
beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl-ol One compound has no
sulfate nor phosphate. Two of the monosulfated compounds have a O-sulfate
on C-6 or on C-4 of the GalNAc residue. The third monosulfated compound
has a novel O-sulfate on C-6 of the Gal residue attached to xylitol. The
two phosphorylated compounds have O-phosphate on C-2 of Xyl-ol, and one
of them has in addition sulfate on C-6 of GalNAc.
=============================================================
37.) In vitro control of neuronal polarity by glycosaminoglycans.
=============================================================
Development 1992 Jan;114(1):17-29
Lafont F, Rouget M, Triller A, Prochiantz A, Rousselet A
CNRS URA 1414, Ecole Normale Superieure, Paris, France.
We have studied the effects of proteoglycans (PGs) and glycosaminoglycans
(GAGs) on the growth and morphology of neurons in culture. PGs from glial
cells or Engelbreth-Holm-Swarm tumor cells (EHS), pure bovine kidney heparan
sulfate (HS), shark cartilage type C chondroitin sulfate (CSc) and bovine
mucosa dermatan sulfate (DS) added to embryonic rat neurons strongly enhanced
total neurite growth after 48 h in vitro. No trophic effects were seen
when PGs treated with a mixture of glycanases were used. PGs, CSc and HS
not only enhanced neurite growth but induced the appearance of a majority
of neurons with a single long axon whereas, in contrast, DS increased dendrite
growth. GAGs bound to the cell surface and were rapidly internalized, a
feature that correlated well with the absence of neurotrophicity of GAGs
previously immobilized on the culture substratum. Although the mechanisms
involved in GAGs neurotrophic effects and in the separate regulation of
neuronal polarity by HS and DS were not elucidated, we found that, as opposed
to HS, DS was able to enhance neuronal adhesion and spreading and to maintain
a high level of expression of microtubule-associated protein 2 (MAP2),
a specific dendritic marker. This finding confirms and extends our previous
observations on the role of adhesion in the regulation of dendrite growth.
=============================================================
38.) A novel angiogenic inhibitor derived from Japanese shark cartilage
(I). Extraction and estimation of inhibitory activities toward tumor and
embryonic angiogenesis.
=============================================================
Cancer Lett 1990 Jun 15;51(3):181-6
Oikawa T, Ashino-Fuse H, Shimamura M, Koide U, Iwaguchi T
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of
Medical Science, Japan.
Guanidine extraction and crude fractionation of Japanese shark cartilage
by ultrafiltration on a molecular weight basis were conducted and the antiangiogenic
activities were assayed as to the inhibitions of tumor and embryonic angiogenesis.
Significant inhibition of angiogenesis was found, and there was a linear
relationship between the results of the two assays. The inhibitory activities
were concentrated in the fraction in the molecular weight range of 103
to 104, and were resistant to heat treatment.
=============================================================
39.) Determination of the distribution of constituent disaccharide
units within the chain near the linkage region of shark-cartilage chondroitin
sulfate C.
=============================================================
Biochim Biophys Acta 1987 Dec 7;926(3):239-48
Uchiyama H, Kikuchi K, Ogamo A, Nagasawa K
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
A method for analyzing the distribution of constituent disaccharide
units within the chain near the linkage region of chondroitin sulfate has
been developed. The method consists of (a) chemical modification of the
reducing terminal residue in the polysaccharide by a 2-(2,4-dinitrophenylamino)ethylamino
(DNP-AEA) group, (b) controlled fragmentation of the DNP-AEA-labeled polysaccharide
with chondroitinase AC-I, followed by separation of the digestion products
into the DNP-AEA-labeled fragments and unlabeled fragments on octyl-Sepharose
CL-4B gel, (c) fractionation of the DNP-AEA-labeled fragments into fractions
having different chain-lengths on Sephadex G-100 (superfine), and (d) determination
of the disaccharide unit composition of the de-dinitropheylated products
(AEA-labeled fragments) by the method combining chondroitinase AC-II treatment
with HPLC analysis. A preparation of shark cartilage chondroitin sulfate
C, which had been characterized well with regard to molecular species (Mr
48,000; average number of repeating disaccharide units (dpav) 93-94; consisting
of chondroitin 6-sulfated 66.8%, 4-sulfated 22.5%, disulfated (D type)
10.3%, and nonsulfated units 0.4%), was analyzed by the above method. On
the basis of the data obtained, distribution features of the disaccharide
units within the chain near the linkage region of the polysaccharide (dpav
27) were estimated. It was, however, difficult to propose a final primary
sequence of the polysaccharide chain, although there was a definite trend
towards an enrichment of 4-sulfated and nonsulfated disaccharide residues
in the area close to the linkage region (dpav 3-9 or 11). This was apparent
together with an enrichment of 6-sulfated and disulfated disaccharide residues
in the area distant from the linkage region (dpav 11 or 13-27).
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40.) Suppression of atherogenesis in hypercholesterolemic rabbits by
chondroitin-6-sulfate.
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Artery 1987;14(6):316-37
Matsushima T, Nakashima Y, Sugano M, Tasaki H, Kuroiwa A, Koide O
2nd Department of Internal Medicine, University of Occupational and
Environmental Health, School of Medicine, Kitakyushu, Japan.
The effect of chondroitin-6-sulfate, obtained from shark cartilage,
on atherogenesis in rabbits fed a high-cholesterol diet was studied. Male
Japanese white rabbits were housed for 10 weeks in three groups, one group
was fed ordinary pellets and was injected intraperitoneally with saline
(standard-diet group), one was fed pellets containing 1% cholesterol and
was injected intraperitoneally with saline (cholesterol-diet group), and
the third group was fed pellets containing 1% cholesterol, and was injected
intraperitoneally with 10 mg of chondroitin-6-sulfate (C-6-S group). Injections
were done daily. The plasma total cholesterol, and cholesterol from very
low-density lipoprotein in the C-6-S group after 5 weeks in the test period,
and low-density lipoprotein cholesterol in the C-6-S group at the end of
the test period were lower than those of the cholesterol-diet group. Significantly
fewer atherosclerotic lesions of the aortic surface were found macroscopically
in the C-6-S group than in the cholesterol-diet group. The cholesterol,
esterified cholesterol and calcium concentrations of the aortic intima-media
in the C-6-S group were significantly lower than in the cholesterol-diet
group. Hydroxyproline levels in these three groups were not different.
The uronic acid concentration of the intima-media in the cholesterol-diet
group was significantly higher than in the C-6-S group (P less than 0.02).
Though the percentage of heparan sulfate on total glycosaminoglycans (GAGs)
of the C-6-S group was lower than in the cholesterol-diet group, there
were no significant differences in the percentages of dermatan sulfate
and chondroitin-4/6-sulfate in total GAGs between the cholesterol-diet
and C-6-S groups. These results suggest that chondroitin-6-sulfate suppresses
cholesterol deposition in the aorta of rabbits fed a 1% cholesterol diet,
probably partly due to a decrease in the plasma low-density lipoprotein
cholesterol, and partly due to a change in arterial metabolism.
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41.) High-field n.m.r. studies of keratan sulphates. 1H and 13C assignments
of keratan sulphate from shark cartilage.
=============================================================
Biochem J 1986 Jun 15;236(3):921-4
Cockin GH, Huckerby TN, Nieduszynski IA
Keratan sulphate was extracted from a shark/whale cartilage preparation
and examined by 400 MHz 1H- and 100 MHz 13C-n.m.r. spectroscopy. Assignment
of the majority of the resonances was facilitated by two-dimensional 13C-1H
correlation by using a modified COLOC procedure and a COSY-45 experiment.
The spectra are consistent with an N-acetyl-lactosamine repeating unit
that is predominantly sulphated at C-6 of both galactose and N-acetylglucosamine.
Gel chromatography of a keratanase digest of the shark keratan sulphate
confirmed the high degree of galactose sulphation.
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42.) Ultrastructural cytochemistry of proteoglycans associated with
calcification of shark cartilage.
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Anat Rec 1984 Feb;208(2):149-58
Takagi M, Parmley RT, Denys FR, Yagasaki H, Toda Y
Proteoglycans (PGs) as well as sulfated glycosaminoglycans (GAGs) are
closely associated with cartilage calcification. An inner zone of endoskeletal
tesserae of sharks is composed of a unique calcified hyaline cartilage.
Initial calcification can be seen in the cartilage close to the inner zone.
We have ultrastructurally examined shark, Triakis scyllia, noncalcifying,
calcifying, and calcified cartilage using the tannic acid-ferric chloride
(TA-Fe), the high iron diamine (HID), and the HID-thiocarbohydrazide-silver
proteinate (HID-TCH-SP) methods for localization of sulfated complex carbohydrates.
In noncalcifying cartilage, TA-Fe and HID strongly stained matrix granules
which were round, ovoid, elongated, or irregularly shaped and presumably
represented PG monomers. The size and staining intensity of the reactive
matrix granules progressively decreased in calcifying cartilage toward
the calcification front of the calcified cartilage. Similarly, a progressive
decrease in the size of the HID-TCH-SP stain deposits in the matrix granules
was observed in the calcifying cartilage close to the calcification front
and was interpreted as a decrease in length of sulfate containing GAG chains.
In the calcified cartilage, the highly calcified areas were often localized
in the calcification front and contained few or no small HID-TCH-SP stain
deposits, whereas the weakly calcified regions contained more stain deposits.
These results indicate that partial and complete degradation of sulfated
GAGs and/or PGs may be a requisite for calcification of shark cartilage.
=============================================================
43.) Distribution of different molecular species of collagen in the
vertebral cartilage of shark (Carcharius acutus).
=============================================================
Connect Tissue Res 1984;12(2):111-8
Rama S, Chandrakasan G
It is known that cartilage collagen in higher vertebrates conforms
to Type II collagen but very little is known of the nature of shark cartilage.
This study was undertaken to determine the differences, if any, between
shark cartilage collagen and that of higher vertebrates. Collagen was obtained
from shark cartilage by pepsin solubilization and characterized by amino
acid analysis and determination of chain composition by SDS-polyacrylamide
gel electrophoresis and CM-cellulose chromatography. Results indicated
the presence not only of Type II collagen but also of Type I collagen.
Type I collagen accounted for about one third of the total collagen content
of shark cartilage.
=============================================================
44.) Shark cartilage contains inhibitors of tumor angiogenesis.
=============================================================
Science 1983 Sep 16;221(4616):1185-7
Lee A, Langer R
Shark cartilage contains a substance that strongly inhibits the growth
of new blood vessels toward solid tumors, thereby restricting tumor growth.
The abundance of this factor in shark cartilage, in contrast to cartilage
from mammalian sources, may make sharks an ideal source of the inhibitor
and may help to explain the rarity of neoplasms in these animals.
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45.) Galactose 6-sulfate sulfatase activity in Morquio syndrome.
=============================================================
Clin Chim Acta 1982 Jul 1;122(2):169-80
Yutaka T, Okada S, Kato T, Inui K, Yabuuhi H
We have prepared a new substrate (o-beta-D-sulfo-galactosyl-(1-4)-beta-D-6-sulfo-2-acetamido-2-deoxyglucosyl-
(1-4)-D-[1-3H]galactitol), from shark cartilage keratan sulfate, for the
assay of galactose 6-sulfate sulfatase activity. Using this substrate,
we found there was a striking deficiency of galactose 6-sulfate sulfatase
activity, in addition to the known deficiency of N-acetylgalactosamine
6-sulfate sulfatase, in the cultured skin fibroblasts of patients with
Morquio syndrome. Our results could be explained by the hypothesis that
accumulation of keratan sulfate and chondroitin 6-sulfate in Morquio syndrome
is due to a deficiency of galactose 6-sulfate sulfatase and N-acetylgalactosamine
6-sulfate sulfatase activity, which are necessary for the degradation of
these two mucopolysaccharides.
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46.) Comparative studies of water sorption of hyaline cartilage.
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Biochim Biophys Acta 1977 Mar 29;497(1):151-9
Mathews MB, Decker L
Vapor phase, water sorption isotherms were obtained for specimens of
bovine, sturgeon and shark cartilage and for membranes composed of collagen
and various proportions of cartilage proteoglycan. The data were interpreted
in the light of an elementary model for swelling of gels which regards
equilibrium swelling a resultant of a balance between contractile forces
of an elastic matrix and expansive forces, principally osmotic in nature.
Swelling ratios for bovine and sturgeon cartilage compared at the same
water vapor pressure are nearly identical, whereas the swelling ratios
for shark cartilage are elevated. These high values are due principally
to a higher ratio of glycosaminoglycan to collagen but also reflect a higher
salt and urea content and possibly also a different type of collagen fibril
network.
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47.) Structure of chondroitin sulfates. Analyses of the products formed
from chondroitin sulfates A and C by the action of the chondroitinases
C and AC from Flavobacterium heparinum.
=============================================================
Biochim Biophys Acta 1976 Dec 21;451(2):436-43
Michelacci YM, Dietrich CP
The structures of chondroitin sulfate A from whale cartilage and chondroitin
sulfate C from shark cartilage have been examined with the aid of the chondroitinases
AC and C from Flavobacterium heparinum. The analyses of the products formed
from the chondroitin sulfates by the action of the chondroitinases have
shown that three types of oligosaccharides compose the structure of chondroitin
sulfate A, namely, a dodeca-, hexa- and a tetra-saccharide, containing
five, two and one 4-sulfated disaccharides per 6-sulfated disaccharide
residue, respectively. The polymer contains an average of 3 mol of each
oligosaccharide per mol of chondroitin sulfate A. Each mol of chondroitin
sulfate C contains an average of 5 mol of 4-sulfated disaccharide units.
A tetra-saccharide containing one 4-sulfated disaccharide and one 6-sulfated
disaccharide C indicating that the 4-sulfated disaccharides are not linked
together in one specific region but spaced in the molecule.
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DATA-MEDICOS/DERMAGIC-EXPRESS No 2-(90) 08/03/2.000 DR. JOSE
LAPENTA R.
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