Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the summer of 1996, an outbreak of Flavobacterium meningosepticum infection developed in a colony of South African clawed frogs (Xenopus laevis). Clinical signs were consistent with septicemia: ascites, anasarca, dyspnea, extreme lethargy, congestion of web vessels, petechial hemorrhages, and sudden death. Mortality rate reached 35%, and all infections were fatal. The organism was resistant to most antibiotics but was susceptible to enrofloxacin, chloramphenicol, and trimethoprim-sulfadiazine. Treatment with trimethoprim-sulfadiazine was unsuccessful. Although the point source of the infection was not determined, several environmental reservoirs were identified, including a communal water barrel and various pieces of equipment. Molecular strain typing by pulsed-field gel electrophoresis and biochemical analyses revealed that frogs were infected with a single strain of F meningosepticum. Sanitation and management procedures were effective in controlling the outbreak.
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PMID:Identification and management of an outbreak of Flavobacterium meningosepticum infection in a colony of South African clawed frogs (Xenopus laevis). 1038 28

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.
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PMID:Developmental toxicity study of glycolic acid in rats. 1053 49

Ethyl methacrylate (ethyl 2-methyl-2-propenoate, EMA) has been implicated in the development of neurologic impairment following occupational exposure. The potential of EMA to produce neurotoxicity was investigated in adult male Sprague-Dawley rats in two experiments. In the first experiment, animals were administered 100, 200, 400, or 800 mg/kg by daily intraperitoneal (i.p.) injections for 60 d. Control rats received daily i.p. injections of 1 ml saline/kg. Clinical observations, spontaneous motor activity, and performance in the Morris water maze were assessed. Alterations in clinical parameters in the higher dose groups included lethargy, impaired breathing, decreased weight gain, and increased mortality. Alterations in motor activity were observed at 100 mg/kg, a dose that did not cause alterations in clinical parameters, body weight gain, or mortality. There was also a dose-dependent impairment in performance in the Morris water maze. In the second experiment, animals were administered EMA in drinking water at concentrations of 0.1, 0.2, or 0.5% for 60 d. Control rats were administered tap water. Animals were perfused at the termination of exposure and samples of brain, spinal cord, and sciatic nerve were prepared for histological examination. Spongiform alterations were observed in fiber tracts of the forebrain, brainstem, and spinal cord. Clusters of axonal swellings were scattered throughout the dorsal, ventral, and lateral columns of the spinal cord, and typically involved internodal segments of two or three neighboring axons. Shrunken axons with separated myelin lamellae and large axons with thinner than normal myelin sheaths were apparent in the sciatic nerve. The patterns of alterations in the white matter of the spinal cord and the sciatic nerve are consistent with myelinopathy, but additional experiments are necessary to confirm whether oligodendroglia and Schwann cells are the primary sites of injury. In addition to the alterations associated with myelin, there was a decrease in the density of neurons in the ventral horn of the spinal cord. While the observed effects of EMA on the nervous system of rats are consistent with neurologic symptoms of workers exposed to EMA, additional experiments are necessary to determine if the level and route of exposures associated with occupational use produce these impairments in experimental animals.
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PMID:Neurotoxicity of ethyl methacrylate in rats. 1065 38

The feasibility of water channel gene delivery to kidney tubules and microvessels was evaluated by delivery of an adenovirus encoding aquaporin 1 (AQP1-Ad5) to transgenic AQP1 null mice. In wild-type mice, AQP1 is expressed in kidney proximal tubule, thin descending limb of Henle, and descending vasa recta, where urine osmolality (Uosm) increases from 1000-1500 mOsm (before) to 2500-3500 mOsm after 36 hr of water deprivation. Uosm in AQP1 null mice remains nearly fixed at 650-750 mOsm. AQP1-Ad5 (with a CMV promoter) was generated and purified. Infection of CHO cells gave strong uniform AQP1 expression with plasma membrane localization and eightfold increased water permeability over noninfected cells. AQP1-Ad5 was delivered to 20 to 25-g AQP1 null mice by tail vein infusion (0-10(10) PFU). At 3-7 days, AQP1 protein expression was strongest in liver (approximately 20 microg of AQP1 protein per liver) and next strongest in kidney, with expression in proximal tubule apical and basolateral membranes, and renal microvessels. Functional analysis showed increased water permeability in apical membrane vesicles from proximal tubule. AQP1 expression was not detected in glomerulus, limb of Henle, or collecting duct. In water-deprived null mice receiving 5 x 10(9) PFU of AQP1-Ad5, Uosm increased by up to 510 mOsm (mean increase, 225 +/- 24 mOsm; n = 33 mice). Whereas the control null mice became lethargic and lost 34.2 +/- 0.6% body weight, the virus-treated mice remained relatively active and lost 32.3 +/- 0.7% body weight. Viral DNA and AQP1 transcript were detected in kidney and liver of null mice up to 17 weeks after virus infusion; partial correction of the urinary concentrating defect persisted for 3-5 weeks. These results demonstrate partial functional correction of a urinary concentrating defect by adenoviral delivery of the AQP1 gene.
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PMID:Partial correction of the urinary concentrating defect in aquaporin-1 null mice by adenovirus-mediated gene delivery. 1072 35

The potential toxicity of RTI 4587-056, a hexahydroindenopyridine analog of SANDOZ 20-438, was examined in adult male Sprague-Dawley rats. Testicular, intestinal, and erythropoietic histology was assessed after 28 days of gavage treatment at 0, 10, and 100 mg/kg/day. During the first 10 days, dose-related clinical signs included mild to moderate lethargy shortly after dosing, lower consumption of feed and water, and body weight loss or decreased weight gain. Tolerance developed, such that lethargy disappeared and weight gains were equivalent to the control group during the second through fourth weeks. The compound did not affect intestinal epithelium or bone marrow. RTI 4587-056 was a highly effective antispermatogenic agent at both doses causing epididymal hypospermia and testicular atrophy. Based upon the Spermatogenic Index ratings, still lower doses would be effective male contraceptive agents. RTI 4587-056 has potential as a male contraceptive without overt side effects. Further testing is required.
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PMID:28-day toxicology test: indenopyridine RTI 4587-056 in male Sprague-Dawley rats. 1083 28

The use of nitrate-contaminated drinking water to prepare infant formula is a well-known risk factor for infant methemoglobinemia. Affected infants develop a peculiar blue-gray skin color and may become irritable or lethargic, depending on the severity of their condition. The condition can progress rapidly to cause coma and death if it is not recognized and treated appropriately. Two cases of blue baby syndrome were recently investigated. Both cases involved infants who became ill after being fed formula that was reconstituted with water from private wells. Water samples collected from these wells during the infants' illnesses contained nitrate-nitrogen concentrations of 22.9 and 27.4 mg/L.
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PMID:Blue babies and nitrate-contaminated well water. 1117 32

The prophylactic effect of in-feed medication of conventional pigs with sulphadimethoxine (SDM), sulphamethoxazole (SMX), and trimethoprim (TMP) was tested by using an Actinobacillus pleuropneumoniae infection model. In each of five experiments, six pigs were given medicated feed twice daily and three pigs received antibiotic-free feed and served as positive (unmedicated, infected) controls. The following drugs or drug combinations were tested (in mg per kg feed): 500 SDM + 100 TMP, 500 SMX + 100 TMP, 125 SMX + 25 TMP, 125 SMX (alone) and 25 TMP (alone). After six days of feed medication, all animals were endobronchially inoculated with A. pleuropneumoniae in a dose of 1-3.10(4) colony-forming units (CFU). The response to the challenge in all control pigs was characterized by fever, lethargy, anorexia, reduced water consumption, and laboured breathing. At autopsy all controls manifested a fibrinous haemorrhagic pleuropneumonia. In-feed medication with 500 SDM + 100 TMP, 500 SMX + 100 TMP as well as 125 SMX + 25 TMP resulted in an effective protection against the challenge in all treated animals. After consumption of feed medicated with 125 mg per kg SMX or 25 mg per kg TMP, pleuropneumonia was evident in all challenged pigs. The results of this study indicate an in vivo potentiation of SMX and TMP in pigs against this respiratory tract pathogen.
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PMID:Prevention of pleuropneumonia in pigs by in-feed medication with sulphadimethoxine and sulphamethoxazole in combination with trimethoprim. 1095 47

Nile crocodiles of three age classes, hatched in captivity and reared in fresh water, when exposed acutely to water of 17 and 35 ppt NaCl, suffered marked dehydration, were lethargic, ceased to feed and lost mass. When exposed to gradually increasing salinities (3-35 ppt), with a short acclimation period at each salinity, crocodiles survived, continued to feed and increased in mass and size. All age classes had a relatively constant plasma osmolality across the salinity spectrum. Cloacal urine osmolality varied throughout the acclimation experiment, but did not increase with increasing salinity. No significant increase was found in plasma concentrations of any of the osmolytes. There was a trend of decreasing cloacal urine [Na(+)] and [Cl(-)] and increasing cloacal urine [K(+)] with increased salinity, indicating that urine was not an important route for Na(+) and Cl(-) excretion. Crocodiles exposed to saline conditions maintained relatively constant plasma uric acid concentrations, but urinary uric acid concentrations increased markedly with increasing salinities. This suggests that uric acid is the main constituent of nitrogenous waste excretion in saline exposed Nile crocodiles. As in Crocodylus porosus, C.niloticus has the physiological ability to survive and thrive in periodically hyper-osmotic environments. However, its euryhalinity is restricted, in that acute exposure to sea water leads to dehydration, but with an acclimation period at lower salinities, it survives and thrives in sea water.
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PMID:Osmoregulation of the Nile crocodile, Crocodylus niloticus, in Lake St. Lucia, Kwazulu/Natal, South Africa. 1096 30

To analyze the physiological functions of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Homozygous mutant Clcnk1-/- mice produced approximately 5 times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24-hour water deprivation, Clcnk1-/- mice became severely dehydrated and lethargic. Intraperitoneal injection of the V2 agonist, deamino-Cys(1), D-Arg(8) vasopressin, induced an increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice from approximately 1,000 to approximately 3,000 mosm/kg H(2)O, whereas the increase in Clcnk1-/- mice was only from approximately 600 to approximately 840 mosm/kg H(2)O, indicating nephrogenic diabetes insipidus in Clcnk1-/- mice. These results clearly established that CLC-K1 plays a major role in the urinary-concentrating mechanisms.
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PMID:Severely impaired urine-concentrating ability in mice lacking the CLC-K1 chloride channel. 1101 33

Mortality among hatchery-reared juvenile white seabass Atractoscion nobilis in southern California, USA, was associated with infections by a Piscirickettsia salmonis-like organism (WSPSLO). Infected fish had no consistent external signs other than pale gills, lethargy and impaired swimming behavior. Internally, the kidney and spleen were enlarged, and some fish had livers with multiple pale foci. Smears from infected kidney, liver, and spleen stained with Wright-Giemsa had intracytoplasmic coccoid organisms, often in pairs, that ranged in size from 0.5 to 1.0 microm. Microscopic lesions included multifocal hepatic, renal, and splenic necrosis, and intralesional macrophages often contained the WSPSLO. The bacterium was isolated from infected fish on cell lines of salmonid (CHSE-214) and white seabass (WSBK) origin. The WSPSLO induced plaque formation and destroyed the cell monolayers within 10 to 14 d incubation at temperatures of 15 and 20 degrees C. The bacterium retained infectivity for cell lines up to 14 d at 4 and 13 degrees C, up to 7 d at 20 degrees C, but it was inactivated at 37 and 56 degrees C within 24 and 1 h, respectively. Freezing at -20 degrees C reduced infectivity by 100-fold. Dehydration and resuspension in distilled water completely inactivated the bacterium. In contrast, the WSPSLO retained nearly all of its infectivity for CHSE-214 cells following a 72 h period in seawater at 20 degrees C. Polyclonal rabbit antibodies made to the WSPSLO reacted specifically in indirect fluorescent antibody tests (IFAT) with the bacterium in cell cultures and smears from infected fish tissues. Tissue smears from infected salmon or CHSE-214 cells with P. salmonis reacted weakly with the anti-WSPSLO serum. Conversely, polyclonal anti-P. salmonis serum produced a weakly positive reaction with the WSPSLO from infected CHSE-214 cells. The WSPSLO as propagated in CHSE-214 cells was highly virulent for juvenile coho salmon Oncorhynchus kisutch, inducing 80% mortality within 10 d of intraperitoneal injection of 10(2.5)-50% tissue culture infectious doses per fish. We conclude that the bacterium from white seabass possesses antigenic differences from P. salmonis yet possesses virulence for salmon equal to known strains of P. salmonis.
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PMID:A Piscirickettsia salmonis-like bacterium associated with mortality of white seabass Atractoscion nobilis. 1114 52


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