Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new male contraception method is undergoing clinical trials in India. The goal of this research is to achieve a method which restricts its effects to the region of the vas deferens. First, the belief that there was a strong peristaltic movement in the vas during ejaculation had to be examined. It was found that only the ampula part of the vas is given a tight squeeze to release the stored sperm into the semen. Therefore, a device to manipulate sperm could safely be inserted into the vas. Using the fact that the acrosomal membrane of the sperm is disturbed when sperm are subjected to electrical currents, Dr. S. K. Guha, of the Indian Institute of Technology in New Delhi, decided to try to generate a current inside the vas to disturb the acrosomal membranes. Since styrene maleic anhydride (SMA) hydrolyses when mixed with body fluids, it creates a slight charge. After injecting SMA into the vas, the electrical balance of the sperm which passes it is disturbed, causing the acrosomal membrane to shrink and rupture, letting water enter the sperm. When the sperm head bursts, the enzymes acrocin and hyaluronidase are released. Without these enzymes, the sperm can not penetrate the ovum and fertility control is achieved. This procedure can be reversed by injecting a solvent to dissolve the SMA in the scrotal sac. Phase I clinical studies began in 1989, and the next Phases should begin soon. The advantages of this method include the fact that no surgical procedure is required, sperm production is not actually blocked so there is no rise in anti-sperm antibody titres, and the contraceptive action can last as long as 10 years. Dr. Guha cautions, however, that education of the people will ultimately play a more important role in population control in India than the availability of a variety of contraceptive methods.
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PMID:Charging the vas deferens -- a novel male contraceptive method. 1217 80

Hyaluronan and its associated water of hydration are the basis of the swelling and edema of acute inflammation. Mystixins are small, synthetic peptides that suppress the acute inflammatory response. Mystixin-7, a prototype of these peptides, has the structure p-anisoyl-Arg-Lys-Leu-Leu-D-Thi-Ile-D-Leu-NH(2). As shown previously by this laboratory, the mystixin-7 peptide inhibits edema formation in vivo following intravenous administration at doses of less than 1.0 mg/kg. Mechanisms by which this peptide might suppress edema were examined here in vitro using cultured cells. Normal human dermal fibroblasts normally secrete large quantities of hyaluronan in response to inflammatory stimuli. Mystixin-7 reduced hyaluronan deposition by up to 80% in such cultures. Stimulation of hyaluronidase activity was observed. Mystixins represent a novel class of anti-inflammatory peptides that suppress the edema associated with inflammation. We propose that stimulation of hyaluronidase activity, with a decrease in net hyaluronan deposition and its associated water of hydration, is among the mechanisms of the anti-inflammatory effect of mystixin peptides.
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PMID:Mystixin peptides reduce hyaluronan deposition and edema formation. 1220 22

Cultured mammalian cells appeared to express specific particles on their surface, which could be detected by their ability to nucleate ice crystals (I-centers) in a newly developed, two-dimensional crystallization assay. Their expression required approximately 24 h independent of cell density, and metabolic energy, and the number and distribution of the I-centers were cell-type specific. Their characteristic ability to nucleate ice crystals was highly sensitive to dehydration, to hyaluronidase and phospholipase C, but not to a number of proteases such as trypsin, chymotrypsin, collagenase, and pronase. However, these proteases, especially pronase, were able to detach the I-centers from the cell surface, without destroying their ability to nucleate ice crystals. I-centers were specific products of live cells, located in relatively small numbers at the cell surface organized in a detachable, sheet-like structure. We propose to consider the ice nucleating ability of I-centers as an expression of their ability to influence the water structure in the surface of cells. Even though their biological function is not known at this time, as water-structuring centers they appear remarkable enough to warrant our attention.
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PMID:Water structuring centers of mammalian cell surfaces. 1224 43

The injection into the dorsal skin of a suspension of guinea pig testis or spermia incorporated in a water-in-oil emulsion containing killed mycobacteria induces aspermatogenesis in guinea pigs. The injury begins with the inhibition of the maturation of spermia and proceeds through the degeneration and exfoliation of spermatids, spermatocytes, and finally spermatogonia. These germinal cells pass from the seminiferous tubules into the epididymis. The process is not associated with inflammation. No significant changes occur in the intertubular spaces and the Leydig cells do not seem to be affected. The seminal vesicles and the prostate remain normal. The aspermatogenesis may begin in 10 days and it lasts for more than 5 months. The process may lead to atrophy of the seminiferous tubules and fibrosis. Guinea pigs which receive a suspension of their own testis or spermia and adjuvants develop a similar injury. The "mitochondrial" fraction of the testis of guinea pig is effective while repeated injections of alcoholic extract of testis emulsified with paraffin oil containing mycobacteria do not cause aspermatogenesis. The presence of acid-fast bacilli in the water-in-oil emulsion containing testis or spermia seems to be essential for the production of testicular lesions; the injection of antigen and mycobacteria into different sites is ineffective. When guinea pig testis is replaced by guinea pig liver or kidney or rabbit testis no testicular damage occurs. The injection of rabbit spinal cord combined with adjuvants results in allergic encephalomyelitis in a large proportion of guinea pigs, accompanied by a great loss of weight. The testes of a few of these animals show a varying degree of aspermatogenesis. When guinea pig brain is combined with adjuvants and administered subcutaneously the incidence of testicular injury is high, although the damage is, in general, mild. From the standpoint of mechanism, the inhibition of spermatogenesis which occurs in these animals may be unrelated to the injury which follows the injection of germinal cells. Aspermatogenesis follows the injection of killed mycobacteria in paraffin oil into the testis as well as into certain sites related to the gonad: the abdominal cavity, the subcutaneous tissue over the abdomen, and the skin of the inguinal region. Antibodies fixing complement in the presence of spermia are demonstrable in the sera of guinea pigs injected with testis or spermia and adjuvants. When the mycobacteria are omitted the titers are low and no testicular injury occurs. Although there seems to be a correlation between testicular damage and complement-fixing titer, this may not be a causal relationship. Antibodies which neutralize guinea pig hyaluronidase and those which immobilize spermia have also been demonstrated in the sera of these guinea pigs.
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PMID:Aspermatogenesis in the guinea pig induced by testicular tissue and adjuvants. 1305 29

Using the death of mice due to the growth of tumor homografts as an end point, the distribution and properties of a tumor homograft-promoting substance(s), the "enhancing substance," were studied. Activity was most largely present in tumor and spleen tissues while that in the liver, kidney, and stomach was relatively slight. Activity was widely distributed in fractions prepared from tumor. Although DNAP and crude RNAP fractions were active, activity could not be associated with either RNA or DNA. The fraction possessing the highest concentration of activity was a residue fraction which was insoluble in water or in dilute or strong saline solutions. Extraction of lyophilized tumor with acetone or 3:1 alcohol:ether reduced, but did not eliminate, activity in the insoluble fraction. However, activity was completely lost after extraction with 80 per cent alcohol at room temperature. Enhancing activity of a tumor fraction was irreversibly lost after exposure for 1 hour to a solution more acid than pH 5 or more alkaline than pH 9. Activity was completely lost after exposure to 50 per cent urea or 90 per cent phenol. Activity was not altered by incubation with trypsin, hyaluronidase, DNAase or the receptor-destroying enzyme of V. cholerae, but it was decreased when trypsin or hyaluronidase was injected with the incubated tumor fraction. Activity was rapidly destroyed by treatment with dilute solutions of sodium periodate at pH 7. Under similar conditions, treatment with KMnO(4) resulted in less extensive destruction of activity while H(2)O(2), K(2)Cr(2)O(7), and NaIO(4) previously inactivated by reaction with glucose had no apparent effect on activity. These results are interpreted as indicating the presence of both carbohydrate and protein in the structure of the activity substance.
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PMID:Studies on a substance that promotes tumor homograft survival (the enhancing substance); its distribution and some properties. 1340 73

Enterococci occur in a remarkable array of environments. They can be found in soil, food, and water, and make up a significant portion of the normal gut flora of humans (10(5)-10(7)/g of stool) and animals. As other bacteria of the gut flora, enterococci can also cause infectious diseases. Most clinical isolates are Enterocococus faecalis, which account for 80-90% of clinical strains. Enterocococus faecium accounts for 5-10% of such isolates. Typical enterococcal infections occur in hospitalised patients with underlying conditions representing a wide spectrum of severity of illness and immune modulation. Enterococci today rank second to third in frequency among bacteria isolated from hospitalised patients. They are isolated from urinary tract infections, intra-abdominal and pelvic infections, bacteremias, wound and tissue infections, and endocarditis--often as part of a polymicrobial flora. Surprisingly, little is known about the factors that contribute to the ability of enterococci to cause infections. Many strains of E. faecalis produce a cytolysin (haemolysin) exhibiting tissue-damaging capacity. Further extracellular products often observed in clinical isolates are a proteinase (gelatinase), hyaluronidase, and extracellular superoxide. Furthermore, many of the clinical isolates possess the aggregation substance on the surface and an extracellular surface protein, both contributing to the adherence to eucaryotic cells. Some strains of E. faecalis, and many E. faecium strains are resistant to multiple antimicrobials. The ultimate role of all these factors in enterococcal pathogenicity remains to be determined. It was previously thought that enterococcal infections were endogenously acquired from the patient's own gut flora. A rather new concept that has emerged is that enterococcal disease is a two-stage process. There is an initial colonisation of the gastrointestinal tract by enterococcal strains possessing virulence traits and/or antibiotic resistance. Subsequently, this population spreads, often facilitated by antibiotic elimination of competitors. For a selected number of patients, there is subsequent tissue invasion from the gastrointestinal tract reservoir. From this concept, it can be deduced that enterococcal strains without virulence traits and antibiotic resistances exogenously transferred into the human gut via food products or probiotics will not represent any risk for immunocompetent individuals. In very severely immunocompromised patients, however, a risk for enterococcal disease by such strains cannot completely be excluded.
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PMID:Safety aspects of enterococci from the medical point of view. 1459 98

Poly(L-lysine)/hyaluronan (PLL/HA) films were chemically cross-linked with a water soluble carbodiimide (EDC) in combination with a N-hydroxysulfo-succinimide (NHS) to induce amide formation. Fourier transform infrared spectroscopy confirms the conversion of carboxylate and ammonium groups into amide bonds. Quartz crystal microbalance-dissipation reveals that the cross linking reaction is accompanied by a change in the viscoelastic properties of the films leading to more rigid films. After the cross-linking reaction, both positively and negatively ending films exhibit a negative zeta potential. It is shown by fluorescence recovery after photobleaching measured by confocal laser scanning microscopy that cross-linking dramatically reduces the diffusion of the PLL chains in the network. Cross linking also renders the films highly resistant to hyaluronidase, an enzyme that naturally degrades hyaluronan. Finally, the adhesion of chondrosarcoma cells on the films terminating either with PLL or HA is also investigated. Whereas the non cross-linked films are highly resistant to cell adhesion, the cells adhere and spread well on the cross-linked films.
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PMID:Improvement of stability and cell adhesion properties of polyelectrolyte multilayer films by chemical cross-linking. 1500 86

This study was designed to identify the specific proteoglycans and glycosaminoglycans (GAGs) in the leaflets and chordae of the mitral valve and to interpret their presence in relation to the tensile and compressive loads borne by these tissues. Leaflets and chordae from normal human mitral valves (n = 31, obtained at autopsy) were weighed and selected portions digested using proteinase K, hyaluronidase, and chondroitinases. After fluorescent derivatization, fluorophore-assisted carbohydrate electrophoresis was used to separate and quantify the derivatized saccharides specific for each GAG type. In addition, the lengths of the chondroitin/dermatan sulfate chains were determined. Proteoglycans were identified by western blotting. The regions of the valve that experience tension, such as the chordae and the central portion of the anterior leaflet, contained less water, less hyaluronan, and mainly iduronate and 4-sulfated N-acetylgalactosamine with chain lengths of 50-70 disaccharides. These GAGs are likely associated with the small proteoglycans decorin and biglycan, which were found in abundance in the tensile regions. The valve regions that experience compression, such as the posterior leaflet and the free edge of the anterior leaflet, contained significantly more water, hyaluronan, and glucuronate and 6-sulfated N-acetylgalactosamine with chain lengths of 80-90 disaccharides. These GAGs are likely components of water-binding versican aggregates, which were abundant in the compressive loading regions. The relative amounts and distributions of these GAGs are therefore consistent with the tensile and compressive loads that these tissues bear. Finally, the concentrations of total GAGs and many different chondroitin/dermatan sulfate subclasses were significantly decreased with advancing age.
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PMID:Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading. 1504 91

Heterotrophic plate counts (HPCs) are commonly used to assess the general microbiological quality of drinking water. Drinking water quality specifications worldwide recommend HPC limits from 100 to 500 cfu ml(-1). A number of recent studies revealed evidence that these bacteria may not be as harmless as generally accepted. It appears that immuno-compromised individuals are particularly at risk. This would include the very young and very old patients with diseases such as AIDS and patients on therapy for purposes such as organ transplantation and cancer treatment. In this study, 339 bacterial colonies were isolated at random from selected treated and untreated drinking water in South Africa using routine heterotrophic plate count tests. In a first step to screen for potentially pathogenic properties, 188 (55.5%) of the isolates showed alpha- or beta-haemolysis on human- and horse-blood agar media. Subsequent analysis of the haemolytic isolates for enzymatic properties associated with pathogenicity revealed the presence of chondroitinase in 5.3% of the isolates, coagulase in 16.0%, DNase in 60.6%, elastase in 33.0%, fibrinolysin in 53.7%, gelatinase in 62.2%, hyaluronidase in 21.3%, lecithinase in 47.9%, lipase in 54.8% and proteinase in 64.4%. Fluorescein and pyocyanin were not produced by any of the isolates. Among the haemolytic isolates, 77.7% were resistant to oxacillin 1 microg, 59.6% to penicillin G 2 units, 47.3% to penicillin G 10 units, 54.3% to ampicillin 10 microg and 43.1% to ampicillin 25 microg. Cell culture studies revealed that 96% of haemolytic isolates were cytotoxic to HEp-2 cells, and 98.9% of the 181 cytotoxic isolates adhered to HEp-2 or Caco-2 cells. HEp-2 cells were invaded by 43.6%, and Caco-2 cells by 49.7%, of the 181 cytotoxic isolates. The invasion index on HEp-2 cells ranged from 1.9 x 10(-1) to 8.9 x 10(-6), whereas the invasion index on Caco-2 cells varied between 7.7 x 10(-2) and 8.3 x 10(-6). The most commonly isolated genera with these potentially pathogenic features were Aeromonas, Acinetobacter, Aureobacterium, Bacillus, Chryseobacterium, Corynebacterium, Klebsiella, Moraxella, Pseudomonas, Staphylococcus, Tsukamurella and Vibrio. The results obtained in this study support earlier findings on potentially pathogenic features of bacteria detected by routine HPCs on drinking water. These findings are in agreement with some epidemiological studies, which indicated an association between HPCs in drinking water and the incidence of gastroenteritis in consumers. However, the extent of the health risk concerned needs to be defined in more detail for meaningful revision of quality guidelines for HPCs in drinking water.
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PMID:Potentially pathogenic features of heterotrophic plate count bacteria isolated from treated and untreated drinking water. 1514 86

Hyaluronan has great potential in medicine as a biomaterial. However, in its native form, hyaluronan is rapidly metabolized in vivo by free radicals and enzymes such as hyaluronidase, and it is highly soluble. Various methods have been adopted therefore, to modify the physicochemical properties of hyaluronan, while maintaining biocompatibility, and thereby widen its spectrum of therapeutic applications. Hyaluronan has four reactive groups (acetamido, carboxyl, hydroxyl and the reducing end) available for crosslinking to itself or other polymers. Using a variety of crosslinking agents, researchers have developed a host of crosslinked hyaluronan derivatives with an increased in vivo residence time. This chemical modification has enabled the production of gels and films, which can be used in applications such as the prevention of post-surgical adhesions, wound healing and dermal augmentation. We have found that if hyaluronan is crosslinked to itself, or to other polymers (either synthetic or biopolymer), in two stages, then a high degree of crosslinking is achieved, conferring improved biostability. In each of the two stages, the same crosslinking agent is used, but different functional groups are bound by altering the reaction conditions. The novel process can be tailored to yield water insoluble gels and films with a broad range of physical and chemical characteristics, and greater resistance to degradation by hyaluronidase and free radicals. These derivatives are currently undergoing biocompatibility testing, and should ultimately lead to a series of innovative second-generation medical products.
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PMID:Synthesis and characterization of a novel double crosslinked hyaluronan hydrogel. 1534 98


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