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The effect of various concentrations of praziquantel at different time intervals post-treatment on the ultrastructure of Schistosoma margrebowiei using scanning and transmission electron microscopy has been examined. The major changes involved blebbing of the entire surface tegument of both sexes (although more marked in males) together with vacuolation of the basal membrane accompanied by the development of membraneous whorls. These effects were progressively more marked with increased concentration and time of exposure resulting in severe erosion of the tubercles and collapse of the sensory organelles. Exposure of the underlying tegumental tissue resulted and paralysis and contraction of the suckers and neck region was apparent. Disruption of the subtegumental musculature and the appearance of vacuolation and membraneous whorl formation were seen. The gastrodermis was similarly affected and the S4 cells of the vitelline gland showed protein disruption of the vitelline droplets. Host cells were seen adhering to the surface of the worms following drug treatment and the synergism between PZQ and the action of the hosts immune system has been discussed.
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PMID:The effect of praziquantel on the ultrastructure of Schistosoma margrebowiei. 188 Mar 89

Onchocerca volvulus worms, extracted from nodules by collagenase digestion, stained with haematoxylin and cleared in glycerol, were unravelled for longitudinal examination and later embedded in brain blocks for study of serial transverse sections. A classification system for female worms is proposed, based on the reproductive status of 446 worms from Guatemala, 94 from Liberia and 125 from Mali. They were categorized into fecund, inseminated specimens; uninseminated, but potentially fertile specimens, shedding ova destined to degenerate; worms changing from the uninseminated to the inseminated state and vice versa, which were few in number; old worms, with degenerate ovaries, whose genital tracts were either empty or had disappeared; and moribund or dead worms, characterized by loss of turgor, collapse and degeneration, calcification, or invasion by polymorphic, basophilic cells. Potentially fertile worms shed oocytes continuously and, when they were inseminated, embryonic development ensured. No evidence was found of a periodic cycle of reproduction. Inseminated worms were found in nodules without a male worm, and uninseminated worms in nodules harbouring male worms. Measurements are recorded of portions of the female reproductive tract and of the length of uterus occupied by the various embryonic stages in fully fecund worms. A significant difference in the length of the body behind the first and second ovaries was observed as between worms from West African savanna (Mali) and forest (Liberia). Limited observations were also made on meiosis in the oocyte, penetration of the oocyte by sperm, formation of the ovum, syngamy and zygote formation.
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PMID:On the reproductive activity of the female Onchocerca volvulus. 207 83

The in vivo effects of oxamniquine on the tegumental surface of adult Schistosoma mansoni were studied using scanning electron microscopy. Pronounced tegumental alterations were observed in all worms including marked oedema, wrinkling and distortion, atrophy, loss of tone and complete disorganization of suckers, blebbing, destruction of tubercles, collapse of sensory papillae and erosion or peeling of the surface layer. The amount of damage was more marked in males than females and varied considerably among worms recovered from the same host and even in different regions of the same worm. Damage was irreversible and all worms were eventually eliminated.
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PMID:Schistosoma mansoni: tegumental surface alterations following oxamniquine treatment of infected mice. 250 53

Amoscanate, when administered orally as an aqueous or "formulated" preparation, induced pronounced ultrastructural abnormalities in male and female Schistosoma haematobium. Higher dose levels of the aqueous suspension (300 mg/kg body wt) had to be administered to achieve the full range of effects induced by formulated doses of 2.5-8 mg/kg body wt. Worms were recovered from hamsters between 1 and 120 hr after treatment. Although the amount of amoscanate-induced damage varied considerably between worms, an overall pattern of damage emerged. Initially, 1 hr after treatment, amoscanate caused tegumental vacuolation and oedema. As the drug treatment period was extended to 24 hr, blebbing, exudation, collapse of sensory organelle bases, and abnormal mitochondria became increasingly evident. With exposure to higher drug doses (50-300 mg/kg body wt), the tegument became further distorted with the appearance of necrotic structures and myelin whorls, which appeared to represent various stages in lysosomal formation and digestion. Eventually, erosion of surface layers resulted in the breakdown of tegumental integrity. The caeca and vitellaria were also adversely affected by drug treatment. Basal vacuolation and the formation of myelin whorls occurred in the gastrodermis. In the mature S4 vitelline cells, coalesced vitelline droplets and myelin whorls were evident.
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PMID:Schistosoma haematobium: amoscanate and adult worm ultrastructure. 650 1

A single dose (1 mg/kg) of milbemycin D was administered orally to 24 dogs with microfilaremia of Dirofilaria immitis, and the number of circulating microfilariae was counted weekly. The number was decreased by 3 to 8% of the pretreatment levels 1 week after the drug administration. The number remained relatively stable for the first 8 weeks and was gradually increased thereafter without returning to the pretreatment levels by 20 weeks. Three or 4 dogs each were euthanatized on day 1, and 1, 4, 8, 12, 16 and 20 weeks after the drug administration to examine the effects of the drug on intrauterine microfilariae and embryos of the worms. Although no intrauterine microfilariae were destroyed directly by the drug, degeneration and collapse of morular embryos and decrease in the number of intrauterine microfilariae were observed 12 after weeks the drug administration. These findings became more remarkable with time, and no intrauterine microfilariae developed in any worms by 20 weeks. The electron-microscopic findings revealed that the nucleoli of oocytes had a high density in the worms of 1, 4 and 8 week groups. Unequal size of cleavage cells and decrease of polysome number were noticed in the early-stage embryos after 8 weeks. It was assumed that the drug might have some effect on the chromosomes or genes in the germinal stem-cell of the heartworm and interfere with protein syntheses, resulting in inhibition of embryonic development. Twelve dogs were given milbemycin D (1 mg/kg) a total of 4 or 6 times monthly according to a prophylactic program.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of milbemycin D on microfilarial number and reproduction of Dirofilaria immitis in dogs. 828 28

Alterations in the tegument of 21-day-old Schistosoma mansoni, caused by artemether administered to the infected mice, were studied using scanning electron microscopy (SEM). Mice were infected with S. mansoni cercariae, and after 21 days a single dose of artemether (400 mg/kg) was administered intragastrically. After 24, 72 h and 7 days groups of three mice were killed and the schistosomules collected by perfusion, fixed and processed routinely, and examined by SEM. After 24 h, all male and female worms examined showed alterations in the tegument, characterised by swelling, vesiculation and fusion of tegumental ridges; peeling, erosion and collapse of damaged tegumental surface, and also destruction of the oral sucker and acetabulum. After 72 h, severe damage to the tegument was seen, usually including extensive peeling, swelling and vesiculation, and host leukocytes were adhered to the damaged surface. Some worms were surrounded by clusters of host leukocytes or had even disintegrated. Seven days after treatment, some schistosomules still showed severe tegumental damage, but in some cases the damage was less than at earlier times, which suggested that those schistosomules that had survived were beginning to recover. The ability of artemether to cause severe damage to the tegument correlates with its high efficacy in killing 21-day-old schistosomules.
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PMID:Tegumental changes in 21-day-old Schistosoma mansoni harboured in mice treated with artemether. 1083 18

The semaphorin family of proteins constitute one of the major cues for axonal guidance. The prototypic member of this family is Sema3A, previously designated semD/III or collapsin-1. Sema3A acts as a diffusible, repulsive guidance cue in vivo for the peripheral projections of embryonic dorsal root ganglion neurons. Sema3A binds with high affinity to neuropilin-1 on growth cone filopodial tips. Although neuropilin-1 is required for Sema3A action, it is incapable of transmitting a Sema3A signal to the growth cone interior. Instead, the Sema3A/neuropilin-1 complex interacts with another transmembrane protein, plexin, on the surface of growth cones. Certain semaphorins, other than Sema3A, can bind directly to plexins. The intracellular domain of plexin is responsible for initiating the signal transduction cascade leading to growth cone collapse, axon repulsion, or growth cone turning. This intracellular cascade involves the monomeric G-protein, Rac1, and a family of neuronal proteins, the CRMPs. Rac1 is likely to be involved in semaphorin-induced rearrangements of the actin cytoskeleton, but how plexin controls Rac1 activity is not known. Vertebrate CRMPs are homologous to the Caenorhabditis elegans unc-33 protein, which is required for proper axon morphology in worms. CRMPs are essential for Sema3A-induced, neuropilin-plexin-mediated growth cone collapse, but the molecular interactions of growth cone CRMPs are not well defined. Mechanistic aspects of plexin-based signaling for semaphorin guidance cues may have implications for other axon guidance events and for the basis of growth cone motility.
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PMID:Molecular basis of semaphorin-mediated axon guidance. 1093 24

Schistosoma mansoni infected mice were treated with naproxen (CAS 22204-53-1) in a dose of 3-4 mg/kg body weight. Treatment was conducted for 7 days before and/or 28 days post infection. Adult worms, developed 7 weeks post infection, were studied by electron microscopy. In both groups, the dorsal surface of the male worms was much more affected by the drug than that of female ones. The most significant morphological degeneration was the change in the aspect and the form of tubercles. Moreover, shrinkage and loss of spines from the ventral surface were also observed. A small portion of the posterior end of female worms showed loss of spines. However, in the first group given naproxen 7 days before infection, the level and extent of changes increased particularly in male worms. There was pronounced oedema, swelling, wrinkling with constriction and collapse of sensory bulbs.
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PMID:Tegumental alterations in Schistosoma mansoni worms induced by treatment of infected mice with naproxen pre- and/or post-infection. 1171 38

Measuring Mirazid ability for contracting the worm muscle and its effect on the worm surface ultra-structure can be used to monitor the in vitro effect of any drug. This study aims at investigating the actual effect of Mirazid (a new schistosomicide; purified oleo-resin extract of Myrrh, derived from Commiphora molmol plant) on S. mansoni worms by detecting its in vitro effect. Three groups of white albino mice (5 mice in each group) were infected by 100 cercariae for each mouse. The 3rd group served as a control group. Seven weeks post-infection the mice were sacrificed, perfused and worms were collected. Muscle tension of the worms collected from the first group of mice, was assayed in response to Mirazid in rising concentrations of 100, 200, 300 and 400 nM. The in vitro effect of Mirazid on the muscle tension of single S. mansoni worm was determined using a special device to determine percentage of change in worm length (% shortening). The drug elicited somatic muscle contraction and reached the highest response with 400 nM Mirazid. The maximal increase in the muscle tension (48% shortening) was induced by the highest concentration (400 nM) of the drug. The worms collected from the second group of mice were scanned by electron microscopy. The worms were exposed each to 10 ul of Mirazid in concentration of 10(-6) and collected after 10, 20 and 30 minutes of exposure. Ten minutes exposure caused disruption of the tegument and collapse of tubercles. After 20 minutes, the tegument appeared edematous with more disruption and more shrinkage of tubercles. After 30 minutes, the tegument appeared markedly edematous with extensive disruption of the inter-papillary areas and sensory bulbs. The spines covering the tubercles appeared to be lost.
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PMID:In vitro effect of Mirazid on Schistosoma mansoni worms. 1470 69

The effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice were compared using scanning electron microscopy (SEM). Forty-two mice infected with S. mekongi for 49 days were treated intragastrically with either 300 mg/kg praziquantel or 300 mg/kg artesunate. Mice were sacrificed 1 or 3 days post-treatment. Worms were collected by perfusion and examined by SEM. One to 3 days after administration of artesunate, the tegument of S. mekongi showed severe swelling, vacuolization, fusion of the tegumental ridges and loss or shortening of the spines on the trabeculae, collapse and peeling. Praziquantel induced similar tegumental alterations as those observed after administration of artesunate, but they were less severe. Three days post-treatment, there was evidence of recovery only in the case of praziquantel. The results of our study suggest that artesunate is more effective than praziquantel in causing tegumental damage in adult S. mekongi, and provides a basis for subsequent clinical trials.
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PMID:Effects of praziquantel and artesunate on the tegument of adult Schistosoma mekongi harboured in mice. 1592 40


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