Standardization of ethanol addiction model in Swiss albino Mice

Background: Addiction is compulsive need for use of a habit-forming substance. World Health Organization (WHO) reported that worldwide 3.3 million people died due to alcohol addiction in 2012-13 and 11% of the population in India indulged in heavy drinking in 2014. Addiction is a prime socio-economical problem of society. Studying alcohol dependence in humans involved many ethical issues and experimental difficulties. Hence nonhuman animal experimental model has been used for a research on the topic of alcohol intoxication and dependence. Ethanol dependence has been preferred to develop in genetically modified strain of mice, C-57 which has a natural inclination to consume and develop addiction. But studying addiction in this special strain requires top end experimental facilities and financial aids. Authors reported the animal model to study ethanol dependence in Swiss albino mice. Aim of the study was to develop ‘Ethanol Dependence in Swiss albino mice animal model’ by intermitted access of 20% ethanol.Methods: Dependence was developed in Swiss albino mice by intermitted access of 20% ethanol in two groups having six animals in each group. Dependence was confirmed by presence of the withdrawal symptoms like anxiety, muscular incoordination and behavioral changes of animals on abstinence of ethanol.Results: Significant difference was noted on withdrawal symptoms, i.e. anxiety, muscular coordination, muscle spasm and other behavior related to withdrawal.Conclusions: Ethanol dependence can be successfully developed in Swiss albino mice in 14 days

Phosducin regulates the expression of transducin betagamma subunits in rod photoreceptors and does not contribute to phototransduction adaptation.

For over a decade, phosducin's interaction with the betagamma subunits of the G protein, transducin, has been thought to contribute to light adaptation by dynamically controlling the amount of transducin heterotrimer available for activation by photoexcited rhodopsin. In this study we directly tested this hypothesis by characterizing the dark- and light-adapted response properties of phosducin knockout (Pd- / -) rods. Pd- / - rods were notably less sensitive to light than wild-type (WT) rods. The gain of transduction, as measured by the amplification constant using the Lamb-Pugh model of activation, was 32% lower in Pd- / - rods than in WT rods. This reduced amplification correlated with a 36% reduction in the level of transducin betagamma-subunit expression, and thus available heterotrimer in Pd- / - rods. However, commonly studied forms of light adaptation were normal in the absence of phosducin. Thus, phosducin does not appear to contribute to adaptation mechanisms of the outer segment by dynamically controlling heterotrimer availability, but rather is necessary for maintaining normal transducin expression and therefore normal flash sensitivity in rods

The effects of second-hand smoke on biological processes important in atherogenesis

BACKGROUND: Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. METHODS: To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB(100 )was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation. RESULTS: "Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein–1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice. CONCLUSION: Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks

Lymphokine enhances the expression and synthesis of Ia antigen on cultured mouse peritoneal macrophages

Steinman, R.M., Nogueira, N., Witmer, M.D., Tydings, J.D., and Mellman, I.S. Lymphokine enhances the expression and synthesis of Ia antigen on cultured mouse peritoneal macrophages. J. Exp. Med. 152: 1248-1261, 1980https://digitalcommons.rockefeller.edu/historical-scientific-reports/1005/thumbnail.jp

Junctional adhesion molecule (JAM)-C deficient C57BL/6 mice develop a severe hydrocephalus

The junctional adhesion molecule (JAM)-C is a widely expressed adhesion molecule regulating cell adhesion, cell polarity and inflammation. JAM-C expression and function in the central nervous system (CNS) has been poorly characterized to date. Here we show that JAM-C−/− mice backcrossed onto the C57BL/6 genetic background developed a severe hydrocephalus. An in depth immunohistochemical study revealed specific immunostaining for JAM-C in vascular endothelial cells in the CNS parenchyma, the meninges and in the choroid plexus of healthy C57BL/6 mice. Additional JAM-C immunostaining was detected on ependymal cells lining the ventricles and on choroid plexus epithelial cells. Despite the presence of hemorrhages in the brains of JAM-C−/− mice, our study demonstrates that development of the hydrocephalus was not due to a vascular function of JAM-C as endothelial re-expression of JAM-C failed to rescue the hydrocephalus phenotype of JAM-C−/− C57BL/6 mice. Evaluation of cerebrospinal fluid (CSF) circulation within the ventricular system of JAM-C−/− mice excluded occlusion of the cerebral aqueduct as the cause of hydrocephalus development but showed the acquisition of a block or reduction of CSF drainage from the lateral to the 3rd ventricle in JAM-C−/− C57BL/6 mice. Taken together, our study suggests that JAM-C−/− C57BL/6 mice model the important role for JAM-C in brain development and CSF homeostasis as recently observed in humans with a loss-of-function mutation in JAM-C

Lymphokine enhances the expression and synthesis of Ia antigens on cultured mouse peritoneal macrophages

Soluble products from antigen stimulated Trypanosoma cruzi-immune spleen cells enhanced the expression of Ia antigens on proteose-peptone-elicited mouse peritoneal macrophages (Mphi). Acquisition of Ia paralleled Mphi activation, previously shown to be mediated by this same source of lymphokine (LK). Expression of Ia and four other plasma membrane antigens was monitored by quantitative binding and radioautographic studies with 125I-monoclonal antibodies. Immune LK selectively enhanced expression of Ia and, to a lesser extent, H-2D relative to control LK from antigen-stimulated noninfected spleen. The levels of three other non-major histocompatibility complex (MHC) antigens, including the trypsin-resistant Fc receptor, were similar in cells exposed to both sources of LK. As little as 1% immune LK induced one-half maximal expression of Ia. Kinetic studies revealed that much of the Ia on freshly explanted peritoneal Mphi was lost during the 1st d of culture. In the continued presence of immune LK, Ia was re-expressed on virtually all Mphi by the 2nd and 3rd d. Alternatively, \u3e95% Ia negative populations were obtained by culturing the cells 3 d; then, addition of LK induced Ia on most cells within 1 d. Once induced, Ia persisted on the Mphi surface for at least 2 d. [ 35S]methionine radiolabeling indicated that immune LK selectively increased radiolabeling of Mphi Ia, again with other non-MHC-linked plasma membrane polypeptides as controls. LK-induced Ia-bearing Mphi were tested as primary mixed leukocyte reaction stimulators. 1 x 10 5-2 x 10 5 Mphi did not stimulate 4.5 x 10 6 responding T cells, whereas 1 x 10 4 dendritic cells induced strong responses, as previously described. Because Ia-positive Mphi do not actively sensitize T cells in a model immune response, we propose that Mphi MHC products serve primarily as recognition sites for previously sensitized T cells, thereby enhancing T cell-mediated Mphi activation

Differential effects of angiotensin II type 2 receptor antagonism in mice models of obesity

Angiotensin II ( ang II) is a vasoactive hormone derived from the renin angiotensin system (RAS), which regulates blood pressure and fluid balance in the body. Ang II effects are mediated via two major receptors: type 1 (AT 1) and type 2 (AT 2). Adipocytes contain a local RAS in which ang II upregulates adipogenesis, fatty acid and triglyceride synthesis primarily mediated via the AT 2 receptor in cultured adipocytes. Preliminary studies from our lab tested the importance of AT 2 receptors in vivo and reported a decrease in adiposity by AT 2 antagonism in the lean, but not the genetically obese db/db mouse. To further explore these effects, we used another genetic model of obesity (ob/ob) and diet-induced obese (DIO) mice and treated them for 2-3 weeks with the AT 2 receptor antagonist, PD 123,319. Body weight, fat pad weight and plasma glucose, leptin and insulin levels and fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPDH) activity were measured. Consistent with previous findings in lean mice, the AT 2 antagonist decreased abdominal fat pad weight in ob/ob mice and accelerated weight loss in D10 mice. Also, correlated with these effects, AT2 blockade decreased FAS activity in ob/ob mice and lowered blood glucose levels in DIO mice. No significant changes were seen in the other parameters that were measured. In combination with recently published data, this research further supports the role of the AT 2 receptor in modulating ang II effects on adipocyte metabolism. Defining this role is crucial in determining and preventing the contribution of adipocyte-derived RAS to systemic disorders such as obesity-related hypertension

T cell-specific suppressor factor(s) with regulatory influence on interleukin 2 production and function

In this study we report that alloantigen-activated spleen cells produce both amplifying and suppressive factors under the same conditions. Both types of soluble mediators--as detected in different assay systems-- were present in the supernatants of in vivo sensitized and in vitro restimulated spleen cell populations and were separable by gel filtration. As shown by others, the amplifying factor (IL 2) was eluted in the size range of 30,000 m.w. The suppressive factor(s) (SF) was eluted in the size range of 10,000 m.w. SF was shown to inhibit the proliferative response of T cells to alloantigen, as well as the generation of regulatory T cells and cytotoxic T cells from their precursors when added at the beginning of the in vitro culture. Furthermore, SF inhibited the release of IL 2 from producer T cells but had no detectable effect on the interaction of IL 2 with receptive T cells. In addition it was shown that SF does not affect the generation of PFC from their precursors after activation by T cell-independent antigens. The results indicate that SF selectively acts on T cells and that it is involved in the regulation of the immune response by modulating early events in T cell activation