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Biomedical subjects

M Bette

Publications and source records attributed to M Bette.

16 recordsLinked to original sources
PubMed2004

Influence of O(3)/O(2)-pneumoperitoneum as an oxidative stressor on duration of anaesthesia, loss of different reflexes and cytokine mRNA expression.

We analysed the effect of intraperitoneal insufflated ozonized oxygen on the anaesthetic strength generated by tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane in male Wistar rats. High dosages of anaesthetic drugs normally used for deep surgical anaesthesia were injected. The ozonized oxygen gas mixture was given five times daily on five consecutive days at 0.8 mg ozone/kg body weight before anaesthesia. The reflexes were measured 15, 30, 60, 90, 120, 180, and 240 min after injection of the anaesthetic drug. The sleeping time and the loss and regain of six different reflexes on noxious and non-aversive stimuli were recorded during the 4 h of observation. O(3)/O(2)-pneumoperitoneum (O(3)/O(2)-PP) reduced the sleeping time induced by tribromoethanol and ketamine/xylazine and increased it for chloral hydrate and pentobarbital. In accordance to the changes in the duration of anaesthesia, the O(3)/O(2)-PP induced significant changes in the loss of different reflexes. Additionally, the modulatory effect of the anaesthetic drugs on splenic cytokine mRNA expression was further influenced by O(3)/O(2)-PP. Thus, the influence of an oxidative stressor on anaesthetic potency and on the resting immune system has to be taken into account for experimental designs in which surgical anaesthesia is necessary for small laboratory animals.

Analysis of Variance↗
PubMed2004

Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen.

We examined the effect of five anaesthetic drugs commonly used in laboratory animal research (tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane) on the expression of four pro-inflammatory cytokines. The anaesthetic agents were applied at dosages normally used for deep surgical anaesthesia. Semiquantitative image analysis of interleukin (IL)-1beta, IL-2, IL-6, and tumour necrosis factor alpha (TNFalpha) mRNA expression in the spleen of male Wistar rats 4 h after application of the anaesthetic drugs showed that these had moderate immunomodulatory effects. Ketamine/xylazine, chloral hydrate, and pentobarbital enhanced the basal expression of IL-1beta and IL-6 mRNA in rat spleen, while urethane reduced splenic IL-1beta mRNA expression. Tribromoethanol, ketamine/xylazine, and urethane reduced the basal TNFalpha mRNA levels, whereas TNFalpha mRNA expression was unaffected by chloral hydrate and by pentobarbital. The data demonstrate that these anaesthetics have slight, but significant, effects on the basal immune status of rats.

Adjuvants, Immunologic↗
PubMed2001

The central nervous system inflammatory response to neurotropic virus infection is peroxynitrite dependent.

We have recently demonstrated that increased blood-CNS barrier permeability and CNS inflammation in a conventional mouse model of experimental allergic encephalomyelitis are dependent upon the production of peroxynitrite (ONOO(-)), a product of the free radicals NO* and superoxide (O2*(-)). To determine whether this is a reflection of the physiological contribution of ONOO(-) to an immune response against a neurotropic pathogen, we have assessed the effects on adult rats acutely infected with Borna disease virus (BDV) of administration of uric acid (UA), an inhibitor of select chemical reactions associated with ONOO(-). The pathogenesis of acute Borna disease in immunocompetent adult rats results from the immune response to the neurotropic BDV, rather than the direct effects of BDV infection of neurons. An important stage in the BDV-specific neuroimmune response is the invasion of inflammatory cells into the CNS. UA treatment inhibited the onset of clinical disease, and prevented the elevated blood-brain barrier permeability as well as CNS inflammation seen in control-treated BDV-infected rats. The replication and spread of BDV in the CNS were unchanged by the administration of UA, and only minimal effects on the immune response to BDV Ags were observed. These results indicate that the CNS inflammatory response to neurotropic virus infection is likely to be dependent upon the activity of ONOO(-) or its products on the blood-brain barrier.

Acute Disease↗
PubMed2001

Absence of spinal response to extracorporeal shock waves on the endogenous opioid systems in the rat.

Extracorporeal shock wave therapy (ESWT) seems to be a new therapeutic strategy for chronic pain due to tendopathies. Neurophysiological mechanisms of action for pain relief following ESWT are still unknown. The aim of this study was to investigate if the analgesic effect of ESWT is caused by modulation of the endogenous spinal opioid system. Rats were treated with two different energy flux densities (0.04 and 0.11mJ/mm(2)) and immunohistochemical analysis of met-enkephalin (MRGL) and dynorphin (Dyn) was performed at 4 or 72 h after ESWT. ESWT had no modulatory influence on the expression of the spinal opioid systems. Different energy doses or repetitive treatment did not alter MRGL or Dyn immunoreactivity in the spinal cord. Furthermore, a delayed effect of ESWT at 72 h after treatment was not detectable. We conclude from these findings that the analgesic effects of ESWT treatment are not supported by endogenous opioids.

Animals↗
PubMed2001

Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents.

Antidepressants produce various immunomodulatory effects, as well as an attenuation of the behavioral responses to immune challenges, such as lipopolysaccharide (LPS). To explore further the effects of antidepressants on neuroimmune interactions, rats were treated daily with either fluoxetine (Prozac) or saline for 5 weeks, and various behavioral, neuroendocrine, and immune functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated the anorexia and body weight loss, as well as the depletion of CRH-41 from the median eminence and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activation. In rats and in mice, which normally display a biphasic body temperature response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished the hypothermic response and facilitated and strengthened the hyperthermic response. The effects of antidepressants on the responsiveness to LPS are probably not mediated by their effects on peripheral proinflammatory cytokine production, because LPS-induced expression of TNFalpha and IL-1beta mRNA in the spleen (assessed by semiquantitative in situ hybridization) was not altered following chronic treatment with either fluoxetine or imipramine. The effects of antidepressants on the acute phase response may have important clinical implications for the psychiatric and neuroendocrine disturbances that are commonly associated with various medical conditions.

Adrenal Glands↗
PubMed2001

Naive and memory T cells migrate in comparable numbers through the normal rat lung: only effector T cells accumulate and proliferate in the lamina propria of the bronchi.

T cells reach the lung via the pulmonary and bronchial arteries that supply the alveolar and bronchial regions. Although these regions are differentially affected by T cell-mediated diseases, the migration of T-cell subsets in these two regions has not been studied. Naive, memory, and effector T cells were injected into congenic rats and traced in sections of normal lung. All three T-cell subsets were found in large numbers in the alveolar region and exited again quickly. Only effector T cells accumulated in the lamina propria of the bronchi. Further, 72 h after injection 6% of the effector T cells still proliferated in the lung, whereas apoptotic effector T cells were only observed 1 h after injection (0.2%). Thus, not only effector and memory but also naive T cells continuously migrated through the lung. The preferential accumulation of effector T cells in the bronchial lamina propria may explain why some diseases preferentially affect the bronchial region.

Animals↗
PubMed1999

Upregulation of COX-2 and CGRP expression in resident cells of the Borna disease virus-infected brain is dependent upon inflammation.

Infection of immunocompetent adult rats with Borna disease virus (BDV) causes severe encephalitis and neural dysfunction. The expression of COX-2 and CGRP, genes previously shown to be implicated in CNS disease and peripheral inflammation, was dramatically upregulated in the cortical neurons of acutely BDV-infected rats. Neuronal COX-2 and CGRP upregulation was predominantly seen in brain areas where ED1-positive macrophages/microglia accumulated. In addition, COX-2 expression was strongly induced in brain endothelial cells and the number of COX-2 immunoreactive microglial cells was increased. In contrast, despite increased expression of viral antigens, neither COX-2 nor CGRP expression was altered in the CNS of BDV-infected rats treated with dexamethasone, or tolerant to BDV. Thus, increased CGRP and COX-2 expression in the BDV-infected brain is the result of the inflammatory response and likely to be involved in the pathogenesis of virus-induced encephalitis.

Animals↗
PubMed1998

Regeneration of implanted splenic tissue in the rat: re-innervation is host age-dependent and necessary for tissue development.

The loss of spleen may lead to fatal bacterial infections. To prevent this, splenic autotransplantation has been performed in humans and experimental animals. However, there is still controversy about the protective function of this procedure. Since innervation plays an important role in splenic function, we investigated whether splenic regenerates are re-innervated, and whether this depends on the donor and host age. Splenic tissue (30 mg) was implanted into the greater omentum of either young (2 days) or old (12 months) rats, from either young or old syngeneic animals. After 3 months of regeneration, the weight of the regenerates was determined, PGP+ nerve fibers were revealed by immunohistology, and subdivided into nerve fibers of sympathetic (TH+, NPY+) or sensory (SP+, CGRP+) origin. In addition, proliferating (Ki-67 proliferation antigen+) and apoptotic cells (TUNEL technique+) were likewise investigated. No innervation of splenic regenerates was observed after implantation into old hosts, correlating with poorly developed splenic compartments. In contrast, almost normal re-innervation occurred in young hosts after implantation of both young and old splenic tissue. These regenerates showed well-developed splenic compartments and a normal number and tissue distribution of proliferating and apoptotic cells. However, after the implantation of young tissue, the final size of splenic regenerates was three times larger (140 +/- 30 vs. 40 +/- 10 mg). Thus, re-innervation of splenic implants is necessary for their subsequent development. It is determined by host age, whereas the final size of the splenic regenerates is regulated by donor age-dependent factors. This model is useful for studying both the process leading to initial innervation and the consequences of this innervation.

Aging↗
PubMed1998

Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system.

To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells, alpha/beta interferon (IFN-alpha/beta) receptors, IFN-gamma receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8+ T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary.

Animals↗
PubMed1996

Intrinsic responses to Borna disease virus infection of the central nervous system.

Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). We speculate that the response of the resident cells of the brain to infection may be involved in the sensitization and recruitment of these inflammatory cells. To separate the responses of resident cells from those of cells infiltrating from the periphery, we used dexamethasone to inhibit inflammatory reactions in BD. Treatment with dexamethasone prevented the development of clinical signs of BD, and the brains of treated animals showed no neuropathological lesions and a virtual absence of markers of inflammation, cell infiltration, or activation normally seen in the CNS of BDV-infected rats. In contrast, treatment with dexamethasone exacerbated the expression of BDV RNA, which was paralleled by a similarly elevated expression of mRNAs for egr-1, c-fos, and c-jun. Furthermore, dexamethasone failed to inhibit the increase in expression of mRNAs for tumor necrosis factor alpha, macrophage inflammatory protein 1 beta, interleukin 6, and mob-1, which occurs in the CNS of animals infected with BDV. Our findings suggest that these genes, encoding transcription factors, chemokines, and proinflammatory cytokines, might be directly activated in CNS resident cells by BDV. This result supports the hypothesis that the initial phase of the inflammatory response to BDV infection in the brain may be dependent upon virus-induced activation of CNS resident cells.

Animals↗
PubMed1994

Localization of kappa-opioid receptor mRNA in neuronal subpopulations of rat sensory ganglia and spinal cord.

A partial cDNA encoding a kappa-opioid receptor was isolated and used to generate specific 35S-labeled probes to investigate the gene expression of the kappa-opioid receptor in sensory, sympathetic and spinal neurons of the rat by in situ hybridization. A subpopulation of mainly small and medium-sized neurons within dorsal root and trigeminal ganglia expressed kappa-receptor mRNA, but no signal was detectable in the superior cervical ganglion. kappa-Receptor mRNA was distributed over neurons throughout the dorsal horn and in laminae VII/VIII. Highest concentrations of positive neurons were seen in laminae I/II, dorsal lamina X and in the lateral spinal nucleus. alpha-Motoneurons and glial cells were not labeled. This distribution of kappa-receptor mRNA indicates preferential functions of kappa-receptors in sensory signalling with particular importance to nociception.

Animals↗
PubMed1994

Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ.

Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly stained single cells, p35 mRNA was expressed in addition weakly in the B cell areas. After injection of LPS or SEB, p40 mRNA was strongly induced in the T cell areas all over the spleen, whereas expression of p35 mRNA and its distribution pattern did not change. Surprisingly, most of the mRNA for p35 and p40 was localized in different areas of the spleen and was apparently produced by different cells. In macrophage-depleted spleens the increased expression of p40 mRNA in response to LPS was reduced but still detectable, demonstrating that other cells besides macrophages can up-regulate IL-12 p40 mRNA. Nude mice showed a stronger expression of p35 mRNA, SCID mice lacked the weak p35 staining of the B cell areas but showed a strong basal expression of both p35 and p40 mRNA and a focal response to LPS. The pattern of IL-12 mRNA expression in beige mice was the same as in normal mice. These data demonstrate a spatial dissociation of expression of the two chains of IL-12 and are compatible with a regulatory role of the isolated IL-12 p40 chain in vivo. In addition, they indicate that the demonstration of mRNA for both chains of IL-12 in whole tissues or cell mixtures is not necessarily indicative of functional IL-12.

Animals↗
PubMed1993

Distribution and kinetics of superantigen-induced cytokine gene expression in mouse spleen.

The polyclonal stimulation of T cells by bacterial superantigens is involved in the pathogenesis of the toxic shock syndrome in certain staphylococcal and streptococcal infections. Here we describe the onset and kinetics of superantigen-induced cytokine production in situ in spleens of normal BALB/c mice monitored at the level of cytokine mRNA expression by in situ hybridization. Messenger RNAs for interleukin 2 (IL-2), interferon gamma, and tumor necrosis factors (TNF) alpha and beta were not expressed at detectable levels in spleens of unstimulated animals but became visible already 30 min after intraperitoneal application of 50 micrograms staphylococcal enterotoxin B. All mRNA levels showed peak expression approximately 3 h after injection and a slow decrease up to 24 h after injection. Expression of the mRNAs was restricted to the T cell-dependent area of the periarteriolar lymphatic sheets of the spleen. Interestingly, TNF-alpha mRNA showed a biphasic response, the early appearing mRNA had the same localization as the other mRNAs, whereas after 3 h TNF-alpha mRNA showed a broader distribution indicating a second cell population producing TNF-alpha. The expression of IL-2 and TNF proteins in the serum increased in parallel to the observed mRNA changes with a slight delay. The presence of macrophages was not required for the expression of the cytokine mRNAs in the spleen as the expression was unchanged in macrophage-depleted mice. Only the second phase of TNF-alpha mRNA expression was abrogated in such animals. The expression of all mRNAs was completely suppressed by prior administration of cyclosporin A. These data show that nonphagocytic cells are the essential superantigen-presenting cells in vivo and indicate that at least part of the pathogenetic TNF-alpha is T cell derived.

Animals↗
PubMedDate not supplied

Possible role of S-100 in glia-neuronal signalling involved in activity-dependent plasticity in the developing mammalian cortex.

Using Western blot analyses and a quantitative ELISA, we identified the presence and developmental accumulation of the astroglial S-100 protein(s) in rat and cat visual cortex. There is a steep rise in the S-100 content, comprising mainly S-100 beta, during the time period of highest cortical malleability in both species. A possible role of the astroglial S-100 protein(s) in experience-dependent plasticity of the visual cortex of kittens was tested by infusing antiserum against this protein during the critical period for cortical malleability. Following 1 week of monocular deprivation, the ocular dominance of single cells in the visual cortex was investigated. The vast majority of cells in the hemispheres infused with anti-S-100 serum maintained binocular responses. This finding suggests that extracellular S-100 protein is essential for ocular-dominance plasticity. Infusion of S-100 beta during the critical period of cortical malleability had no effect on deprivation-induced ocular-dominance plasticity, but interfered with the experience-dependent refinement of orientation selectivity of visual cortical neurons. It is suggested that S-100 beta may play an important role in the refinement of cortical circuitries by selectively affecting active or activated neuronal compartments. As S-100 beta is synthesized in astroglial cells, the effects on neuronal plasticity imply that glia-neuronal information transfer occurs during activity-dependent plasticity. Possible underlying mechanisms are discussed on the basis of current knowledge on the S-100 protein family, especially S-100 beta (Marshak, 1990).

Aging↗
PubMedDate not supplied

Repetitive pneumoperitoneum with ozonized oxygen as a preventive in lethal polymicrobial sepsis in rats.

The aim of this study was to test whether repetitive pretreatments of rats with ozonized oxygen at relatively low gas volumes into the abdomen (20 ml per rat per day) have any beneficial or detrimental effects on the course of a polymicrobial-induced lethal peritonitis. Peritonitis was induced in a surgical or a nonsurgical model by usage of fecal material from the cecum. As the biological read out we used the mortality analysis. To include possible mechanisms by which ozone might influence the septic outcome, we characterized the gene expression of the pro-inflammatory cytokines IL-1beta, IL-2, and TNF-alpha mRNA in lymphoid organs. In both models, we found a significant beneficial influence of a dose-dependent O(2)/O(3 )pneumoperitoneum on the survival rate when compared to control animals or to room air. The ozone-enhanced survival seems to be independent from altered cytokine expression because there were no differences noticed in the levels of bacterial-induced gene expression of IL-1beta and TNF-alpha in septic animals pretreated with ozonized oxygen when compared to control animals.

Animals↗