Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation.

Stress often occurs during toxicity studies. The perception of sensory stimuli as stressful primarily results in catecholamine release and activation of the hypothalamic-pituitary-adrenal (HPA) axis to increase serum glucocorticoid concentrations. Downstream effects of these neuroendocrine signals may include decreased total body weights or body weight gain; food consumption and activity; altered organ weights (e.g., thymus, spleen, adrenal); lymphocyte depletion in thymus and spleen; altered circulating leukocyte counts (e.g., increased neutrophils with decreased lymphocytes and eosinophils); and altered reproductive functions. Typically, only some of these findings occur in a given study. Stress responses should be interpreted as secondary (indirect) rather than primary (direct) test article-related findings. Determining whether effects are the result of stress requires a weight-of-evidence approach. The evaluation and interpretation of routinely collected data (standard in-life, clinical pathology, and anatomic pathology endpoints) are appropriate and generally sufficient to assess whether or not changes are secondary to stress. The impact of possible stress-induced effects on data interpretation can partially be mitigated by toxicity study designs that use appropriate control groups (e.g., cohorts treated with vehicle and subjected to the same procedures as those dosed with test article), housing that minimizes isolation and offers environmental enrichment, and experimental procedures that minimize stress and sampling and analytical bias. This article is a comprehensive overview of the biological aspects of the stress response, beginning with a Summary (Section 1) and an Introduction (Section 2) that describes the historical and conventional methods used to characterize acute and chronic stress responses. These sections are followed by reviews of the primary systems and parameters that regulate and/or are influenced by stress, with an emphasis on parameters evaluated in toxicity studies: In-life Procedures (Section 3), Nervous System (Section 4), Endocrine System (Section 5), Reproductive System (Section 6), Clinical Pathology (Section 7), and Immune System (Section 8). The paper concludes (Section 9) with a brief discussion on Minimizing Stress-Related Effects (9.1.), and a final section explaining why Parameters routinely measured are appropriate for assessing the role of stress in toxicology studies (9.2.).

https://journals.sagepub.com/doi/pdf/10.1177/0192623312466452

Interpreting Stress Responses during Routine Toxicity Studies: A Review of the Biology, Impact, and Assessment

The gastrointestinal tract is innervated by several distinct populations of neurons, whose cell bodies either reside within (intrinsic) or outside (extrinsic) the gastrointestinal wall. Normally, most individuals are unaware of the continuous, complicated functions of these neurons. However, for patients with gastrointestinal disorders, such as IBD and IBS, altered gastrointestinal motility, discomfort and pain are common, debilitating symptoms. Although bouts of intestinal inflammation underlie the symptoms associated with IBD, increasing preclinical and clinical evidence indicates that infection and inflammation are also key risk factors for the development of other gastrointestinal disorders. Notably, a strong correlation exists between prior exposure to gut infection and symptom occurrence in IBS. This Review discusses the evidence for neuroplasticity (structural, synaptic or intrinsic changes that alter neuronal function) affecting gastrointestinal function. Such changes are evident during inflammation and, in many cases, long after healing of the damaged tissues, when the nervous system fails to reset back to normal. Neuroplasticity within distinct populations of neurons has a fundamental role in the aberrant motility, secretion and sensation associated with common clinical gastrointestinal disorders. To find appropriate therapeutic treatments for these disorders, the extent and time course of neuroplasticity must be fully appreciated.

Neuroplasticity and dysfunction after gastrointestinal inflammation

The effects of physiologically relevant increase in temperature (37–41°C) on intestinal epithelial tight junction (TJ) barrier have not been previously studied. Additionally, the role of heat-shock...

https://www.physiology.org/doi/pdf/10.1152/ajpgi.00401.2005

Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability.

The pubertal development of the hypothalamic-pituitary-adrenal (HPA) axis has received relatively little experimental attention. As puberty is marked by an increase in the susceptibility to various psychiatric disorders that may be related to HPA dysfunction, it is imperative to elucidate the pubertal development of this neuroendocrine axis. To date, the limited research in this area has been conducted primarily on males. Presently, we investigated stress responsiveness, as measured by both stress hormones (e.g., corticotropin (ACTH) and corticosterone) and gonadal steroids, in intact and ovariectomized prepubertal and adult female rats before and after a 30-min session of restraint stress. We report here that intact prepubertal females exhibit an extended corticosterone stress response (30-45 min longer) compared to intact adults. Moreover, ovariectomized prepubertal females continue to exhibit a prolonged stress-induced corticosterone and progesterone response compared to ovariectomized adults, indicating these protracted responses prior to puberty are independent of ovarian hormones. ACTH levels were not significantly different between intact and ovariectomized prepubertal and adult animals at all the post-stress time points measured, suggesting that the prolonged corticosterone response in prepubertal females is due to an enhanced sensitivity to ACTH at the level of the adrenal cortex. Taken together, these data indicate that stress reactivity changes dramatically during puberty in females. Furthermore, these data demonstrate additional development of the HPA axis during pubertal maturation, resulting in a more quickly terminated stress response in adulthood.

Differential stress reactivity in intact and ovariectomized prepubertal and adult female rats.

The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.

Effect of acute heat stress on rat adrenal glands: a morphological and stereological study

In order to evaluate the relationship between water quality in ponds and indices of histopathological changes occurring in the vital organs of the common carp (Cyprinus carpio L., 1758), two six-month field experiments were carried out using two different water supplies: from the nearby stream and a tube well. The fish were fed supplemental feed: raw cereals, pelleted and extruded compound feed. Histopathological analysis, alteration frequencies, and semi-quantitative scoring of the changes were used to assess the health status of the fish. Ponds supplied by stream water were characterized by higher water hardness, dissolved oxygen and pH values, while those supplied by the tube well had higher electroconductivity, total ammonium and orthophosphates content. Fish survival rate and habitat suitability index were lower in ponds supplied by stream water, while the weight gain did not differ between the two water supplies. The use of stream water resulted in a higher level of histopathological changes in gills and liver. Among the water quality parameters, pH level had the strongest influence on fish. Differences in water supply produced greater influence on the level of histopathological changes than the type of feed applied. Gills were the most sensitive organ, while the kidney was the least responsive.

/pdf/histopathological-indicators-a-useful-fish-health-monitoring-2luyf4jkh3.pdf

Histopathological indicators: a useful fish health monitoring tool in common carp ( Cyprinus carpio Linnaeus, 1758) culture

Background/aims In this study, we present radioimmunoassay data describing the concentration of Vasoactive Intestinal Polypeptide (VIP) in both plasma and colonic biopsies, as well as immunostaining of VIPergic innervation in mucosal biopsies of normal subjects and patients with ulcerative colitis (UC). Patients and methods Thirty three patients with UC and 17 healthy subjects were investigated. All UC patients suffered from active disease. Fasting circulating levels of VIP in plasma as well as tissue concentrations were measured by radioimmunoassay. For the immunohistochemistry, polyclonal antibody against VIP and the streptavidin-biotin peroxidase complex technique were carried out. Results Overall plasma VIP concentrations in the UC patients were similar to those in the controls. Significantly decreased concentrations of VIP were found in UC of rectum compared to the normal tissue. However, both plasma VIP values and tissue concentrations were found to be significantly lower in patients expressing minimal or mild active disease according to clinical activity index (AI) and histological activity index (HAI), but marked increase of plasma VIP was clear in UC patients with moderate or severe AI and HAI. There was a trend towards increased tissue concentrations of VIP in the group of patients with moderate or severe AI and HAI. Our immunohistochemical analysis of VIP fibers and nerve cell bodies revealed consistently weaker VIP-immunoreactivity in the rectum in UC patients with minimal or mild HAI. Simultaneously, in the rectal biopsies from UC patients with moderate and severe disease, the fibers in the lamina propria and ganglion cells in the submucous plexus were markedly increased in density and in degree of immunostaining. Very strong immunoreactivity was also found in inflammatory cells of the lamina propria as well as in the epithelial layer of the biopsies from UC patients with obvious disease. Conclusions Our study shows clearly the heterogeneity in the response of VIP plasma level as well as rectum concentration and distribution in UC patients at different stages of the active disease. The possible role of VIP in the colon suggests that further studies of the alterations of this gut peptide may be useful in the understanding of UC pathophysiology.

Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis-A radioimmunoassay and immunohistochemical study

Acute ethanol treatment increases level of progesterone in ovariectomized rats.

Quantitative analysis of the light microscopic and fine structure of rat islet B-cells was carried out in chronic alcoholism. Absolute pancreatic weight and volume were similar in groups C (control) and E (ethanol), but relative pancreatic weight in group E rat was decreased. The results for fasting blood glucose and insulin levels were similar in the two groups of animals. There was a significantly reduced total pancreatic islet volume in E rats. The total number of endocrine cells both per islet and per microns2 of islet was similar in the two groups of animals. The volume density and number of B-cells per islet and per microns2 of islet were not changed in ethanol-treated rats as compared with the control. On the other hand, diameter, surface area and volume of the B-cells and their nuclei were found to be statistically significantly decreased. Histological examination revealed that islet blood vessels were dilated in alcoholic rats. Over the 4-month period of ethanol intake a significant decrease in cell profile area, nuclear profile area and volume density of cytoplasmic granules and an increase in the profile area and volume density of endoplasmic reticulum occurred. The gross histological alteration seen in most B-cells of the ethanol-treated rats was irregularity of the nuclear envelope with deep invagination and with margination of heterochromatin and many empty granules or granules without clear electron dense crystals of insulin. The present results indicate some optical and structural abnormalities of B-cells in chronic alcoholism that may be related to cell dysfunction and may contribute, at least in part, to the endocrine pancreas functional disturbance.

/pdf/rat-pancreatic-b-cells-after-chronic-alcohol-feeding-a-6wxe9dgvgn.pdf

Vesna Koko

Papers

Effect of acute heat stress on rat adrenal glands: a morphological and stereological study

Histopathological indicators: a useful fish health monitoring tool in common carp ( Cyprinus carpio Linnaeus, 1758) culture

Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis-A radioimmunoassay and immunohistochemical study

Acute ethanol treatment increases level of progesterone in ovariectomized rats.

Rat pancreatic B-cells after chronic alcohol feeding. A morphometric and fine structural study.