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[
J Parasitol,
1975]
At various time periods after an initial exposure to 50 Brugia malayi larvae on one hind foot cats were reexposed to an additional 50 larvae in one of 3 ways: on the previously infected limb only, on the contralateral, uninfected limb only, or on both hind limbs simultaneously. At the time of reexposure uninfected controls were exposed to 50 larvae on one hind foot in a similar manner. From 2 to 4 weeks after reexposure to larvae, the cats were necropsied and the appropriate lymph nodes and vessels examined for adult or developing worms. An existing infection in one limb did not influence early migration or development of larvae introduced into the contralateral leg. Previous infection in the same limb did not consistently result in decreases in the number of developing larvae from the second exposure but did alter the distrubution of larvae. In repeat infections, larvae were consistently located in a moe distal area of the limb than were larvae from an initial infection at a comparable time.
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[
Am J Trop Med Hyg,
1975]
Forty-one experimental and 37 control cats were each infected with 50 Brugia malayi larvae in such a way that a preponderance of the larvae remained localized in the popliteal lymph node or in the lymphatics of the leg draining into that node. During the 1st week after infection cats were treated with varying doses of diethylcarbamazine citrate (DEC). Two weeks after infection, necropsy for worm recovery was performed on treated and control cats. No living larva was recovered from 21 of 22 cats treated with a total of 10 mg DEC/kg body weight or greater. A single living larva was recovered in only 2 of 5 cats treated at 5 mg/kg. At 2 mg/kg, 8 of 10 cats had substantially fewer larvae than their controls; the remaining 2 were negative. In 4 cats treated with a total of 1 mg/kg, there was no reduction of larvae. All 37 untreated controls harbored living larvae, with a mean of 56% of the inoculum being recovered.
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[
Am J Trop Med Hyg,
1979]
Sixty-three experimental and 58 control cats were infected with Brugia malayi so that the developing and adult worms localized in the regional lymphatics of the hind legs. At 20 days after infection when Brugia were in the 4th larval stage, and at 8 weeks when worms were young adults, cats were divided into groups to test the efficacy of diethylcarbamazine citrate (DEC) at various dosage levels. At 100 mg total DEC/kg no 4th-stage larvae were seen in 5 cats compared with a mean of 20.4 living larvae in each of 5 controls. At this level of DEC, 2 of 5 cats had 1 and 2 adult worms while 4 of 4 controls had a mean of 23.2 living adult worms. At 50 and 25 mg/kg there was a substantial reduction of both 4th stage and adult worms when compared to controls. At 10 mg/kg, 4 of 6 cats had 4th-stage larvae but at a lower level (mean = 7.0) than in 6 controls (mean = 23.2). No reduction of either 4th-stage larvae or adult worms was seen at 1 mg/kg. This study establishes the efficacy of DEC against 4th-stage and adult Brugia malayi in cats, although considerably higher levels of the drug were required than the level previously determined to kill 3rd-stage larvae. It appears that the cat-B. malayi model will be an effective method to compare the efficacy of drugs against adult lymphatic-dwelling filariae.
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[
Am J Trop Med Hyg,
1983]
Cats with patent infections of Brugia malayi were treated by intraperitoneal injection of diethylcarbamazine citrate (DEC) for 6 consecutive days, weekly for 6 consecutive weeks or monthly for 3 months. Each cat received a total of 100 mg DEC per kg. At necropsy 7 months after infection, no living worms were recovered from any of eight cats treated weekly and only one of nine cats treated daily had a single living Brugia. Five of nine cats treated monthly and six of eight untreated controls had one or more living worms. Cats treated weekly showed a larger decline in microfilariae than those of the other treated groups. The mean microfilariae level of untreated controls increased 2-fold. At necropsy, gross appearance of regional lymphatics in daily and weekly treated cats resembled those of uninfected controls more closely than those in cats treated monthly or untreated. Differences in degree of histological changes between groups of infected cats were not apparent. Weekly administration of DEC appeared to be the most effective regimen; monthly treatment was less effective.
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[
Lymphology,
1988]
Domestic cats and patas monkeys were infected with Brugia malayi so that the worms localized in the regional lymphatics of the hind legs. Reaction to the filarial parasites resulted in visible local edema in cats and disruption of normal lymph flow in the monkeys. Edematous tissue was examined grossly and by light and electron microscopy. Lymph flow patterns were examined by direct observation following injection of lymph staining dye and reflection of the skin, by X-ray following injection of radio-opaque contrast media, and by lymphscintigraphy after subcutaneous injection of radioisotopes. Clinical edema occurred in cats but not in monkeys. However, disruption of normal lymph flow in monkeys infected with Brugia could be demonstrated by lymphscintigraphy.
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[
Southeast Asian J Trop Med Public Health,
1973]
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Microcirc Endothelium Lymphatics,
1985]
Infection with filarial nematodes induces lymphatic dysfunction in many individuals in endemic areas. The present morphometric study describes changes in lymphatic endothelial cells of Brugia-infected cats. Transmission electron microscopy revealed a decrease in the number of cytoplasmic vesicles in endothelial cells from lymphatic vessels harboring filarial nematodes (4.9 vesicles per micron 2 cytoplasm) when compared with similar cells from the contralateral uninfected control vessels (9.0 vesicles per micron 2). The size of the vesicles and their location within the cytoplasm was not changed. Irregular large vacuoles, often containing degenerating organelles, were common in endothelial cells lining Brugia-infected lymphatic vessels. These studies suggest that damage of cells by living or dead worms or worm products may have a direct effect on the endothelial lining of lymphatic vessels. This may compromise the efficiency of vessels that collect and transport edematous fluid in affected limbs.
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Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO
[
Sci Rep,
2021]
The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).
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[
Front Pharmacol,
2020]
Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.
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[
Naturwissenschaften,
2004]
Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.