Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To facilitate biochemical, pharmacological, and biophysical studies on the membrane of the body muscle of Ascaris suum, a method for preparing intact vesicles was developed. Vesicles were prepared by incubating a muscle flap preparation with 1 mg/ml collagenase in a saline solution and then washing in saline without enzyme. The vesicles then formed gradually over the next hour as outgrowths of the original surface membrane from the bag region of the muscle. The vesicles were harvested readily by suction using a Pasteur pipette. The structure of the vesicles was examined with the transmission electron microscope. The whole-cell patch-clamp technique showed that the vesicles had a high input resistance and that the membrane was complete. The vesicle membrane was shown to contain Ca-activated Cl channels and gamma-aminobutyric acid-activated Cl channels. The vesicles also were shown to be suitable for fluorescence recovery after photobleaching studies designed to examine lateral and vertical movement of a lipid probe (5-N [octadecanoyl]-aminofluorescein) in the membrane. This probe had a mean lateral diffusion coefficient (DL) of 8.1 x 10(-9) cm2/sec, but only a proportion (68.4%) of the probe was mobile. The latter observation illustrated the nonuniform nature of the membrane. Ivermectin (10(-7) M) had no effect on DL or percent recovery. Trypan blue quenching experiments showed that the lipid probe remained in the outer monolayer of the membrane. These observations illustrate the experimental value of the vesicles; they are potentially useful in discerning anthelmintic mode of action and in drug screening.
 ...
PMID:Surface properties of membrane vesicles prepared from muscle cells of Ascaris suum. 169 73

Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes.
 ...
PMID:Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin. 186 Jan 46

This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted.
 ...
PMID:Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus. 226 70

Uterine and skin derived forms of microfilariae (mf) and earlier developing stages of the cattle filarial nematode Onchocerca gutturosa were examined for the lectin binding properties of their external surfaces (ie. egg shell and microfilarial cuticle). Both the uterine and skin derived forms of mf failed to bind any of the lectins tested. Incubation in known microfilaricides did not promote any binding of lectins to these parasites. Peanut agglutinin (PNA) was the only lectin found to bind specifically to earlier developing stages (i.e. the shells of freshly obtained eggs). Diethylcarbamazine (DEC) did not alter the binding pattern from that observed in untreated eggs. Ivermectin eliminated PNA binding but increased Ricinus communis lectin (RCA-1) positivity. Trypsin, collagenase and protease enzymes all affected the binding; chitinase however did not have any effect. These results support the concept that the eggshells of filariae can interact with the host defence responses.
 ...
PMID:Lectin binding to the developing forms of Onchocerca gutturosa microfilariae. 282 17

A range of culture conditions were examined to optimize parasite maintenance. Using male worms in a cell-free system, good results were obtained with medium NCTC 135 + 10% inactivated calf serum (IFCS) in an atmosphere of 95% N2/5% CO2 (median survival time 45 days). Survival was increased to 6-7 months using medium MEM + 10% IFCS + LLCMK2 (monkey kidney) feeder cells in a gas phase of 5% CO2 in air. Worms exposed to collagenase solution (5 mg/ml) were subsequently less motile and survived shorter periods compared to unexposed controls. The drug responses of worms (in vitro) were examined using 13 antiparasitic compounds. Ivermectin and CGP 6140 were among the most active, with the majority of drugs significantly affecting motility levels at a concentration of 5 x 10(-5) M or less. This system may provide useful information on the intrinsic activity of new compounds. A technique was developed for the successful cryopreservation of males in liquid nitrogen using ethanediol as a cryoprotectant in a 2-step incubation procedure, thereby enabling the long-term storage and transportation of worms. In conclusion, the common bovine parasite O. gutturosa provides a practical alternative for research in the absence of O. volvulus.
 ...
PMID:The development of a laboratory model for onchocerciasis using Onchocerca gutturosa: in vitro culture, collagenase effects, drug studies and cryopreservation. 285 98