Post-mortem changes in the abomasal mucosae of sheep infected with Haemonchus contortus compared with those in uninfected sheep

Progressive post-mortem changes were observed, with fibre optic endoscopy, in the abomasum of uninfected sheep and sheep infected with H. contortus. Loss of epithelial cells was observed 14 to 16 min after death in the uninfected sheep. The loss exposed the underlying lamina propria. This loss became more widespread as the time after death increased. Epithelial cell loss was observed earlier (as early as 6 min after death) in the infected sheep. Three of the infected sheep also displayed dispersal of alkaline phosphatase activity 30 min after death. The present work shows that post-mortem changes can occur quite quickly in animals, especially infected animals, and emphasizes the importance of rapid removal of tissue from animals after death.     

Renin secretion in the earliest stage of goldblatt-type hypertension in rats

Summary Unilateral nephrectomy and constriction of the remaining renal artery in the rat induced a sustained increase of systolic blood pressure, which becomes significant as soon as 90 minutes after operation, and a transient rise in renal venous as well as in peripheral plasma renin activity between 20 and 180 minutes after operation. Unilateral nephrectomyper se, after 90 and 180 minutes, caused a significant fall of the systolic blood pressure, a slight increase of renal venous renin activity after 20 and 45 minutes, and between 3 and 24 hours after operation it was followed by a significant decrease of peripheral plasma renin activity. An increased secretion of renin from the clamped kidney may thus contribute to the initial rise of blood pressure in rats with Goldblatt-type hypertension.Supported by Fonds National Suisse de la Recherche Scientifique, Grant No. 53153.     

Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo

Background Administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We recently developed a guinea pig model for propranolol-induced bronchoconstriction (PIB). Neuropeptides which are released from C-fibre nerve endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective The purpose of this study was to examine whether sensory neuropeptides are involved in the development of PIB after allergic reaction. Methods Propranolol at a concentration of 10mg/ml was inhaled 20min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea pigs. The animals were treated intravenously with a NK₁ and NK₂ dual antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK₁ antagonist, FK888, in a dose of 1 or 10mg/kg or vehicle 10min before or 15min after antigen challenge. Results Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after antigen challenge as well as 10 min before antigen challenge did not reduce the PIB. Conclusion We conclude that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of PIB after allergic reaction.     

Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis

The relationship between inflammation and proteolytic activation in pancreatitis is an unresolved issue in pancreatology. The purpose of this study was to define the influence of neutrophils on trypsinogen activation in severe AP. Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. For neutrophil depletion, an anti-Gr-1 antibody was administered before pancreatitis induction. Administration of the anti-Gr-1 antibody reduced circulating neutrophils by 97%. Pancreatic TAP and serum amylase levels increased 2 h and 24 h after induction of pancreatitis. Neutrophil depletion reduced pancreatic TAP and serum amylase levels at 24 h but not at 2 h after pancreatitis induction. Pancreatic MPO and infiltration of neutrophils, as well as MIP-2 levels, were increased 24 h after taurocholate infusion. Two hours after taurocholate administration, no significant pancreatic infiltration of neutrophils was observed. Injection of the anti-Gr-1 antibody abolished MPO activity, neutrophil accumulation, and MIP-2 levels, as well as acinar cell necrosis, hemorrhage, and edema in the pancreas at 24 h. Moreover, taurocholate-provoked tissue damage and MPO activity in the lung were normalized by neutrophil depletion. Intravital fluorescence microscopy revealed a 97% reduction of leukocytes in the pancreatic microcirculation after administration of the anti-Gr-1 antibody. Our data demonstrate that initial trypsinogen activation is independent of neutrophils, whereas later activation is dependent on neutrophils in the pancreas. Neutrophils are critical in mediating pancreatic and lung tissue damage in severe AP.     

The effect of acute and chronic exercise on thyroid hormones in obesity

Thyroid hormones were measured before, during and after acute exercise (60 min) or physical training (3 months) in obese women. Thyroid stimulating hormone concentration increased during acute work and decreased immediately after. No changes were seen during the two following days. An increase was seen after ten days as well as after three months of physical training. Thyroxine concentrations showed no changes. 3,5,3'-Triiodothyronine decreased slightly immediately after acute exercise, and after three months of physical training, 3,3',5'-triiodothyronine (reverse triiodothyronine) increased slowly during and after acute exercise. A negative correlation was found between changes in fasting insulin and thyroxine and a positive correlation between changes in blood pressure and triiodothyronine after training. Lack of agreement in previous reports is probably due to methodological differences such as methods more or less susceptible to fatty acid interference, and thyroid hormones changing differently during acute work and before and after physical training. The duration of the study may also be of importance, even 3 months possibly being too short for attaining equilibrium in thyroid homeostasis.     

大鼠创伤性脑损伤中内皮性脂酶表达变化 

目的 探讨内皮性脂酶(EL)在创伤性脑损伤(TBI)后的表达变化及定位情况.方法 应用健康成年SD大鼠40只,成功制备TBI模型31只.通过Western blotting检测脑损伤后EL表达的时相变化,免疫荧光化学方法检测EL在脑组织中的细胞定位.结果 Western blotting显示,大鼠脑损伤后,EL表达逐步增高,伤后3d升至最高点,之后逐渐下降,于损伤后2周时降至最低水平;免疫荧光双标记结果显示EL与神经元的标记物NeuN共定位.与凋亡相关的蛋白Caspase-3和Bcl-2在TBI后表达发生变化,并且细胞凋亡趋势与EL表达变化趋势基本一致.结论大鼠TBI后,EL表达增加,推测EL可能参与脑损伤后神经再生及神经元凋亡过程.     

Observations of absorption of immunolactoglobulins in calves.

The aim of this study was to ascertain whether administration of one liter of stilulated saliva from a healthy cow as first food to newborn calves blocks absorption of immunolactoglobulins administered later in colostrum or milk. The study material consisted of 12 calves, divided into two groups, one of which received colostrum, and the other milk. Blood samples were drawn immediately after birth and 3 and 6 hours after administration of saliva and 3 and 6 hours after administration of colostrum (group I) or milk (group II). Only some of the calves of each group absorbed immunolactoglobulins from colostrum or milk. In these calves, immunoglobulins could be demonstrated in their serum as early as 3 hours after birth. Absorption of immunolactoglobulins was independent of their concentration in food as their levels were similar in calves fed colostrum or milk. The experiment failed, however, to give an unequivocal answer to the question whether feeding calves before the first administration of colostrum restricts or inhibits absorption of immunolactoglobulins from colostrum.     

Mechanisms of Pathogenesis in Listeria monocytogenes Infection V. Early Imbalance in Host Energy Metabolism During Experimental Listeriosis

Early changes in hepatic carbohydrate metabolism without apparent hepatocyte dysfunction were reported previously in mice infected with Listeria monocytogenes. This study was undertaken to examine possible imbalance in host regulatory mechanisms which might be responsible for these changes. Female CD-1 mice fasted 12 hr prior to the experiments were injected intraperitoneally with 10(5), 10(6), or 10(7)Listeria. Control mice received either 10(9) heat-killed Listeria or 150 mug of Salmonella typhimurium lipopolysaccharide. Hepatic glycogen, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and nicotinamide adenine dinucleotide (NAD) (NAD(+), NADH, NADP(+), and NADPH) levels were assayed periodically. Activities of ATP hydrolyzing enzyme and NAD glycohydrolase were measured at various intervals after infection. Decreases in glycogen occurred as early as 10 hr after infection. Responses in the controls differed from those in infected mice. Hepatic ATP levels decreased as early as 10 hr after infection, with concomitant increases noted in ADP. Hepatic ATP hydrolyzing enzyme activity increased as the infection progressed. Decreases were noted in hepatic NAD levels, with the greatest reduction in the reduced form of NAD. Slight changes were observed after 10 hr, and greater differences were noted 20 hr after infection. The magnitude of these biochemical changes appeared to be dose-dependent. Significant increases in hepatic NAD glycohydrolase activity were noted as the infection progressed. Small but significant increases in serum inorganic phosphate were noted 10 and 20 hr after infection, with a larger increase observed 30 hr after infection. The results indicate impairment of host energy metabolism early in the course of experimental listeriosis.     

Function of Sox2 in ependymal cells of lesioned spinal cords in adult zebrafish

The sex-determining region Y-box 2 (Sox2) is related not only to pluripotency, but also to cell proliferation. Zebrafish can regain their motor function after spinal cord injury (SCI). Following SCI, new motor neurons are produced from proliferating ependymal cells. Here, we investigated the expression and function of Sox2 after SCI in zebrafish. Sox2 was upregulated as early as 1 day post-lesion (dpl) in ependymal cells, which was followed by cell proliferation. Sox2 knockdown significantly decreased the number of proliferating cells at 5 dpl. The results of this study suggest a role of Sox2 as one of the proliferation initiators in ependymal cells after SCI.     

Hepatic sinusoidal cell destruction in the development of intravascular coagulation in acute liver failure of rats

Rats received a dose of dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4). In the liver of rats given DMN, apoptosis of fat-storing cells occurred at 7.5 h, and sinusoidal endothelial cell degeneration followed, with parenchymal cell necrosis after 9 h. Fibrin thrombi appeared in the sinusoids as well as in these necrotic areas after 12 h. In contrast, in the liver of rats given CCl4, parenchymal cell degeneration was seen after 6 h and necrosis with fibrin thrombi developed after 9 h. Fat-storing cells and endothelial cells were almost intact, and fibrin thrombi were not present in the sinusoids. SGPT values increased with decreased plasma levels of fibrinogen and antithrombin III and prolonged prothrombin time after 3 and 6 h, in the CCl4 and DMN models, respectively. An extensive reduction in plasma factor VIIIC levels and peripheral platelets was seen after 18 and 24 h, respectively, only in the DMN model. These results suggest that endothelial cells destruction can cause fibrin formation in the hepatic sinusoids in acute liver injury. Fat-storing cell injury may contribute to the destruction.     

Upregulation of ICAM-I by Plasmodium falciparum: in vitro and in vivo studies.

AIMS--To monitor the expression of intercellular adhesion molecule I (ICAM-I) in vitro after stimulation of human macrophages with Plasmodium falciparum antigens, as well as the plasma concentrations of soluble ICAM-I (SICAM-I) in vivo in malarial patients. METHODS--Human mononuclear leucocytes were cultured and stimulated for four hours with 300 ng/ml exogenous P falciparum antigens. CD14 and CD54 (ICAM-I) expression was monitored using flow cytometry. Soluble ICAM-I (s ICAM-I) was also measured in the blood of 122 outpatients with malaria before and after treatment (Rio Branco, Acre, Brazil). RESULTS--ICAM-I expression increased from 15% to 375% after four hours of stimulation. When sICAM-I was analysed in the plasma of 122 patients with P falciparum or Plasmodium vivax malaria by enzyme immunoassay, significant increases were found. These were more pronounced in patients with P falciparum malaria, compared with healthy controls, and with the same patients four weeks after treatment. CONCLUSION--ICAM-I expression may also be upregulated in human macrophages by exogenous Plasmodium antigens as well as by cytokines during the acute phase of malaria. sICAM-I concentrations are downregulated after treatment, probably caused by the absence of circulating Plasmodium antigens.     

Metabolic activity in human alveolar macrophages increases after cessation of smoking

Alveolar macrophages (AMs) were recruited by bronchoalveolar lavage (BAL) from human smokers before and one, three, and six months after smoking cessation. The metabolic activity of the AM was quantified as luminol-enhanced chemiluminescence (CL) both at rest and after in vitro stimulation with phorbol myristate acetate (PMA). The resting CL values did not differ before and after smoking cessation. The activity after PMA stimulation was unaltered at one and three months. However, the maximal metabolic response, as well as the rate, were significantly (P < 0.02 andP < 0.01, respectively) higher at six months, compared to prior smoking cessation. In addition, the time to reach the maximal peak was reduced after six smoke-free months, indicating a more rapid cell activation. The cell concentration in the BAL-fluid decreased (P < 0.001) as soon as after one smoke-free month and remained low at the following lavages. The lower metabolic response one and three months after smoking cessation, and the increased response six months after, together with a rapid normalization of the cell concentration in the BAL fluid, may be explained by the persistence of tobacco-smoke particles in the alveolar space, which could influence cell activity.     

The course of allergen-induced leukocyte infiltration in human and experimental asthma

BACKGROUND: Although the timing of allergen-induced bronchoconstriction is well defined, there is little information about the kinetics of allergen-induced leukocyte infiltration in asthma and its comparability between human and animal models of asthma. OBJECTIVE: To investigate systematically allergen-induced leukocyte infiltration into the airway lumen in human and experimental asthma by using bronchoalveolar lavage. METHODS: Patients with allergic asthma were lavaged at different time points as long as 1 week after segmental allergen challenge. Allergen-sensitized mice were lavaged as long as 3 weeks after allergen challenge. Differential cell counts, lymphocyte subsets, and cytokines were assessed in bronchoalveolar lavage fluid. RESULTS: In both models, neutrophil infiltration was a relatively early event (maximum: 18 hours after challenge). In contrast, eosinophil infiltration peaked 42 hours (human model) to 4 days (mouse model) after allergen challenge, paralleled by an IL-5 peak in this period. There were elevated macrophage counts over a period of several days after allergen challenge in both models. Lymphocytes (predominantly CD4+ T cells) peaked 18 hours after challenge in the human model, but not until 2 weeks after challenge in the murine model. CONCLUSION: Early neutrophil accumulation (within hours after challenge) and delayed eosinophil accumulation (within days after challenge) in the airway lumen are common features of allergen-induced airway inflammation, whereas lymphocyte kinetics are dependent on the asthma model. CLINICAL IMPLICATIONS: Similarities in the infiltration kinetics of granulocytes after allergen challenge suggest a common role for these cells in asthma, whereas the presumed orchestration of allergic inflammation by lymphocytes appears to differ between the models.     

Comparison of changes in testosterone concentrations after strength and endurance exercise in well trained men

Summary Changes in the testosterone concentrations after single sessions of endurance and strength training were measured in seven well trained men, experienced in both forms of training. Both training sessions were rated as hard to very hard on the Borg scale. Blood samples for testosterone measurements were taken before, immediately after, and 2, 4 and 6 h after the training sessions as well as the next morning. The mean tes tosterone concentration increased 27% (P<0.02) and 37% (P< 0.02) during the strength and endurance training session, respectively. Two hours after the training sessions the mean testosterone concentration had re turned to the pre-training level and remained at that level for the length of the observation period. There were no significant differences in the changes in testosterone concentration after strength and endurance training but there were large differences in the testosterone response at the level of the individual. A high correlation (r=0.98;P<0.001) for individuals was found between increases in testosterone concentration after strength and after endurance training. It was concluded that the changes in mean testosterone values followed the same timecourse after single sessions of strength and endurance training of the same duration and perceived exertion. The interindividual differences in tes tosterone response may be of importance for individual adaptation to training.     

Sequential changes in the expression of genes involved in lipid metabolism in adipose tissue and liver in response to fasting

The aim of this study was to provide a sequential analysis of the expression patterns of key genes involved in lipid metabolism in white adipose tissue (WAT) and liver and their relationship with blood parameters in response to fasting. Adult male rats were studied under different feeding conditions: feeding state, after 4, 8, or 24 h fasting, and after 3 h refeeding after 8 h fasting. Blood parameters and the expression of genes involved in lipogenesis and lipolysis in WAT and liver were analyzed. mRNA levels of genes involved in lipogenesis in liver (SREBP1c, FAS, and GPAT) had already decreased after 4 h fasting, as well as those of PPARgamma in WAT, whereas the decrease in SREBP1c, FAS, GPAT, and GLUT4 mRNA levels in WAT was observed after 8 h. Concerning lipolytic and fatty-acid-oxidation-related genes, liver PPARalpha, FGF21, CPT1, and PDK4 mRNA levels increased after 8 h fasting and those of ACOX1 after 24 h, and in WAT, ATGL, and CPT1 mRNA levels were greater after 24 h. Three hours refeeding increased the expression levels of PPARgamma in WAT, SREBP1c in both liver and WAT, and GPAT in liver, and decreased the expression levels of PPARalpha, CPT1, and PDK4 in liver. These results give new insight into the different adaptive time course response to fasting in the expression of genes involved in lipid metabolism, thus pointing out the very rapid response of lipogenic genes, particularly in liver, and the later response of lipolytic genes, particularly in WAT.     

The significance of complete decortication in the development of anaphylactic shock in dogs

Summary Following unilateral decortication, the condition of sensitization and anaphylactic shock develops in dogs with the same doses of antigen (horse serum) as in intact animals. Fifteen days after removal of the second hemisphere the intensity of the shock reaction, appearing as a result of introduction of the same dose of the antigen was greatly decreased. One month after complete decortication the manifestations of anaphylaxis were even less pronounced. The intensity of anaphylactic shock was especially low six months after bilateral decortication. This demonstrates that bilateral decortication decreases the reactivity of the animal organism to the antigenic stimulus.Presented by Active Member Acad. Med. Sci. USSR V.N. Chernigovskii     

Morphometrical variations of prolactin cells in response to prolonged and systemic administration of Met-enkephalin in female rats

Summary A stimulatory effect on prolactin secretion had been describe after acute and systemic administration of met-enkephalin, but the effects of this opioid after chronic administration has not been reported, and the response of mammotroph cells is not clear. As a complement to previous studies, a morphometric analysis (light and electron microscopy) was carried out on prolactin cells from female rats treated chronically with met-enkephalin. Clear features of cellular hyperactivity appeared after chronic and systemic administration of the opioid, and these persisted for two weeks. The changes consisted in increases of cellular, cytoplasmic and nuclear areas, volume and surface densities of the Golgi complex and rough endoplasmic reticulum, as well as the numbers of exocytotic figures. These morphological alterations were paralleled by an increase in serum prolactin levels as detected by RIA. It is concluded that the increase in the synthesis and secretory activity of prolactin cells following chronic and systemic administration of met-enkephalin is very similar to those observed after acute and intraventricular administration.     

Embryonic stem cells inhibit expression of erythropoietin in the injured spinal cord

Recent observations have demonstrated neuroprotective role of erythropoietin (Epo) and Epo receptor in the central nervous system. Here we examined Epo function in the murine spinal cord after transplantation of pluripotent mouse embryonic stem (ES) cells pre-differentiated towards neuronal type following spinal cord injury. Expression of Epo was measured at both mRNA and protein levels in the ES cells as well as in the spinal cords after 1 and 7 days. Our data demonstrated that expression of Epo mRNA, as well as its protein content, in ES cells was significantly decreased after differentiation procedure. In the spinal cords, analysis showed that Epo mRNA level was significantly decreased after 1 day of ES cell injections in comparison to media-injected control. Epo protein level detected by Western blot was diminished as well. Examination of Epo production in the injured spinal cords after media or ES cells injections by indirect immunofluorescence showed increased Epo-immunopositive staining after media injections 1 day after injection. In contrast, ES cell transplantation did not induce Epo expression. Seven days after ES cell injections, Epo-immunopositive cells’ distribution in the ipsilateral side was not changed, while the intensity of immunostaining on the contralateral side was increased, approaching levels in control media-injected tissues. Our data let us to presume that previously described immediate positive effects of ES cells injected into the injured zone of spinal cord are not based on Epo, but on other factors or hormones, which should be elucidated further.     

葫芦素B对大鼠肝细胞凋亡的保护作用

目的观察葫芦素B对脂多糖(LPS)所致大鼠肝细胞凋亡的保护作用.方法用光镜、TUNEL染色和流式细胞仪(FCM)检测肝细胞凋亡.结果LPS1.4mg/kg,ip后8h出现凋亡细胞增多,16h达到高峰,24h降低.凋亡细胞主要分布在中央静脉周围及肝包膜下.葫芦素B0.1mg/kg或0.2mg/kg在给LPS后立即sc能明显减少凋亡细胞数,以0.2mg/kg组作用最显著.结论葫芦素B可通过抑制肝细胞凋亡产生保肝作用.     

A study in the maintenance phase of ischaemic acute renal failure in the rat

The fate of the trapped deformed erythrocytes seen in the early recirculation phase after ischaemia and the generation of long Tamm-Horsfall (TH) cylinders in the renal medulla during the first week after recirculation was studied in rats. In an in-vitro study the effects of different concentrations of TH protein on the permeability to Na+ of a semipermeable membrane were also investigated. The trapping of erythrocytes was found to be a reflow phenomenon, as there was no increase in the capillary area of the medulla in kidneys subjected to ischaemia but with no recirculation. This area increased to a maximum of 34.6 +/- 2.07% 20 min after recirculation and decreased to a normal value of 3.3 +/- 0.74% 1 day after the primary ischaemia. The area occupied by cylinders increased to a maximum of 19.2 +/- 1.4% 2 days after the primary damage and was as large as 16.7 +/- 1.47% after 1 week. It was also shown that the diffusion half-time of Na+ ions across a semipermeable membrane increased from 11.4 +/- 0.45 min to a maximum of 32.2 +/- 2.19 min with a protein concentration of 1 mg ml-1. It was concluded that the trapping of erythrocytes alone could not explain the decrease in renal function 1 week after the primary damage, but that the blockade of the tubules by the long homogeneous TH cylinders could be responsible for this decrease.