Immunopathologic changes in the thymus during the acute stage of experimentally induced feline immunodeficiency virus infection in juvenile cats.

The feline thymus is a target organ and site of viral replication during the acute stage of feline immunodeficiency virus (FIV) infection. This was demonstrated by histologic, immunohistologic, flow cytometric, and virologic tests. Thymic lesions developed after 28 days postinoculation (p.i.) and included thymitis, premature cortical involution, and medullary B-cell hyperplasia with germinal center formation and epithelial distortion. Alterations in thymocyte subsets also developed. Fewer CD4+ CD8- cells were detected at 28 days p.i., while an increase in CD4- CD8+ cells resulted in an inversion of the thymic CD4/CD8 ratio of single-positive cells, similar to events in peripheral blood. Provirus was present in all thymocyte subpopulations including cortical CD1(hi), CD1(lo), and B cells. The CD1(hi) thymocyte proviral burden increased markedly after 56 days p.i., coincident with the presence of infiltrating inflammatory cells. Increased levels of provirus in the CD1(lo) thymocyte subpopulation were detected prior to 56 days p.i. This was likely due to inclusion of infected infiltrating inflammatory cells which could not be differentiated from mature, medullary thymocytes. Proviral levels in B cells also increased from 70 days p.i. Morphologic alterations, productive viral infection, and altered thymocyte subpopulations suggest that thymic function is compromised, thus contributing to the inability of FIV-infected cats to replenish the peripheral T-cell pool.     

Biochemical changes in rat testis induced in vitro by reactive oxygen species

We report the effects of reactive oxygen species generated by ultraviolet-A radiation on some biochemical parameters specific for oxidative stress, in rat testis homogenates. Results show an increase in lipid peroxidation products under ultraviolet-A exposure, and suggest that the involved mechanism is typical for a radical-mediated chain reaction. The amount of SH groups also increases during irradiation, probably as a consequence of conformational changes in proteins. Electrophoresis results revealed protein pattern changes mainly in the low molecular weight domain. The catalytic activities of alkaline phosphatase and gamma-glutamil transpeptidase are modified under the oxidative conditions generated by reactive oxygen species. The changes of the enzymatic activities are UVA exposure time-dependent, suggesting that conformational modifications are responsible for enzymatic activities enhancement.     

Involution of the rat thymus in experimentally induced hypothyroidism

The thymus, as part of the immune-neuroendocrine axis, is greatly influenced by factors from most endocrine glands, especially the thyroid. Antithyroid drugs (carbimazole and methimazole) were used to induce hypothyroidism in rats. Histological and ultrastructural examination of the thymus showed progressive thymic involution after 4 weeks of drug treatment to the end of observations (7 weeks). The involution was characterised by increased thymocyte apoptosis and thymocyte phagocytosis by macrophages. This resulted in thymocyte depopulation, increases in numbers of interdigitating cells, alterations to mainly subcapsular and medullary epithelial cells, an apparent increase of mast cells and collagen in the capsule and septa, and increased numbers of B cells and plasma cells. Lymphoid cells immuno-reactive with MRC OX12 (which detects B cells) were observed within blood vessel walls, suggesting that they may have been moving in and out of the thymus. The administration of drugs causing hypothyroidism, therefore, also caused marked involution of the thymus.     

大剂量顺铂所致大鼠急性肾衰过程中肠道细菌易位与肠内菌群比例变化的关系

目的研究大剂量顺铂(cisplatin,DDP)所致大鼠急性肾功能衰竭过程中肠道细菌易位与肠内菌群比例变化的关系。方法SD大鼠24只,雌雄各半,依体重随机分为DDP用药后24、48、72 h组和NS对照组,每组6只。10 mg/kg DDP单次腹腔内注射,等量生理盐水对照。随后观察并记录大鼠用药后的表现及体重变化情况;DDP用药后不同时间点分别取用药组大鼠和对照组大鼠,称重后内眦静脉取血,生化法检测血清尿素氮和肌酐的浓度;无菌条件下剖腹取回盲部淋巴结进行细菌培养;同时取十二指肠、空肠、回肠和结肠段内容物进行细菌涂片检查。结果大剂量DDP用药后6 h大鼠体重开始降低,用药48 h后出现腹泻症状并进行性加重。DDP用药后48 h大鼠出现血尿素氮、肌酐的比例显著升高,与对照组比较差异有非常显著性(P0.01)。DDP用药后24 h66%的大鼠回盲部淋巴结出现革兰阴性菌生长,用药后48 h革兰阴性菌生长的阳性率为83%,而对照组大鼠则无细菌生长。对照组大鼠十二指肠、空肠和回肠内主要以革兰阳性球菌为主,结肠内主要以革兰阴性杆菌和革兰阳性球菌为主。DDP用药后24 h,十二指肠、空肠、回肠和结肠内仍然以革兰阳性球菌为主;用药48 h后,空肠、回肠和结肠内革兰阴性杆菌所占比例逐渐增加。结论大剂量DDP可导致大鼠肠道细菌易位、空肠、回肠和结肠内菌群比例失衡,可能与大鼠内毒素血症及急性肾功能衰竭的发生、发展及恶化有关。     

Apoptotic differences in experimentally induced colorectal rat tumours

The presence of apoptotic bodies and of intraepithelial lymphocytes (IELs) were assessed in colorectal adenomas and adenocarcinomas induced in 158 rats by two different carcinogens: 1,2 dimethylhydrazine (DMH) and glutamic acid pyrolysate (GLU-P-1 and 2). Apoptotic granules were present in 97.5% ( n=40) of the 41 GLU-induced adenomas and adenocarcinomas, but only in 20.5% ( n=24) of the 117 DMH-induced tumours. IELs were found in 95.1% ( n=39) of the 41 GLU-induced tumours but only in 21.4% (n=25) of the 117 DMH-induced neoplasias. The differences were significant ( p< 0.001). The presence of IELs and apoptotic granules in GLU tumours (and their absence in the majority of the DMH tumours) is new evidence that IELs are the cells from which many of the apoptotic granules — seen in colorectal neoplasias — derive. GLU neoplasias were induced following daily treatment, for 24 months (about half the life span of the animals) and DMH neoplasias by weekly doses, for a period of only 2.8-6 months. It would appear that 'slowly growing' colorectal GLU neoplasias often attract IELs and trigger lymphocytic apoptosis whereas 'quickly growing' DMH tumours seldom evoke those reactions.     

Seasonally and experimentally induced changes in testicular function of the Australian bush rat (Rattus fuscipes)

Serum concentrations of LH, FSH and testosterone were measured monthly throughout the year in male bush rats. Testicular size and ultrastructure, LH/hCG, FSH and oestradiol receptors and the response of the pituitary to LHRH were also recorded. LH and FSH rose in parallel with an increase in testicular size after the winter solstice with peak gonadotrophin levels in the spring (September). The subsequent fall in LH and FSH levels was associated with a rise in serum testosterone which reached peak levels during summer (December and January). In February serum testosterone levels and testicular size declined in parallel, while the pituitary response to an LHRH injection was maximal during late summer. The number of LH/hCG, FSH and oestradiol receptors per testis were all greatly reduced in the regressed testes when compared to active testes. In a controlled environment of decreased lighting (shortened photoperiod), temperature and food quality, the testes of sexually active adult males regressed at any time of the year, the resultant testicular morphology and endocrine status being identical to that of wild rats in the non-breeding season. Full testicular regression was achieved only when the photoperiod, temperature and food quality were changed: experiments in which only one or two of these factors were altered failed to produce complete sexual regression.     

Biochemical and immunological changes in guinea pigs with experimentally reproduced amyotrophic leukospongiosis

Biochemical blood serum tests at different stages of amyotrophic leukospongiosis have shown differences in lactate and pyruvate levels as well as in lactate dehydrogenase activity, indicative of the increased oxidative exchange in sick guinea-pigs. It is suggested that intensified glycolysis is a compensatory-adaptive reaction in response to hypoxia due to respiratory disorders (spinal type) and degeneration and death of motoneurons. Leukospongiosis was accompanied by the decline in the complement level in the blood serum and production of antibodies to nervous fiber proteins.     

Inhibition of the glycogen phosphorylase system during ochratoxicosis in chickens

Graded doses of ochratoxin A incorporated into the diet (0, 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/g) of broiler chickens significantly (P < 0.05) inhibited activity of protein kinase, the initiator enzyme of the glycogen phosphorylase system, in the livers at all dose levels. Only the highest dose, 8.0 micrograms/g, significantly reduced the total activity of phosphorylase kinase, which is activated by protein kinase. The total activity of phosphorylase, which is activated by phosphorylase kinase, was unaltered by ochratoxin A at any level. Additon of ochratoxin A to liver extracts control birds inhibited protein kinase but not phosphorylase kinase. When added to extracts of livers from control birds, cyclic adenosine 3',5'-monophosphate stimulated protein kinase but not phosphorylase kinase. The cyclic adenosine 3',5'-monophosphate had no effect when added to extracts from birds fed ochratoxin A. These results suggest that ochratoxin A affects primarily the cyclic adenosine 3',5'-monophosphate-dependent protein kinase which initiates the enzymatic cascade leading to glycogenolysis. Furthermore, these results conform an earlier assignment on morphological criteria of the glycogenosis of ochratoxicosis as a type X glycogen storage disease.     

Mitochondrial functions during experimentally induced cardiac hypertrophy

When the hearts of albino rats are subjected to pressure-induced stress through constriction of ascending aorta, changes in the mitochondrial functions are observed as early as 24 h after the imposition of the stress. These include the abolition of oxidative phosphorylation, decrease in the energy dependent [⁴⁵Ca]-uptake and decrease in the rate of energized swelling. A large influx of calcium ions and an increase in the fluidity of mitochondrial membranes also occur in this period. At later stages of hypertrophy (17, 28, 40%), these mitochondrial functions gradually return to normal levels.     

Decreased glycogen mobilization during ochratoxicosis in broiler chickens.

Graded doses of pure ochratoxin A (0, 0.5, 1.0, 2.0, 4.0, and 8.0 microgram of toxin per g of feed) were incorporated into a commercial diet which was fed to chickens from hatching to 3 weeks of age, at which time the experiments were terminated. Liver glycogen levels were elevated significantly (P less than 0.05) by 4.0 and 8.0 microgram/g but not lower doses. Glucagon stimulation of glycogen mobilization was inhibited at the same concentrations. Histopathological examination revealed cytoplasmic but not nuclear deposits of glycogen in cells at the periphery of liver lobes. These data demonstrated that ochratoxin inhibited glycogenolysis. Impaired ability to generate glucose from glycogen could account for the increased susceptibility to cold stress previously reported to occur in ochratoxicosis. Based on present and prior observations, it seems possible that ochratoxin induces a syndrome which mimics the glycogen storage disease of type X which is caused by a deficiency in the cyclic AMP-dependent enzyme of the glycogenolytic enzymatic cascade.