Anticancer Activity of New Copper (II) Complexes with 6-Thiguanine Drug

Abstract: A new complex has been synthesized of Cu (II) complex with 6-thioguanine and phyico-chemical characterized by amperometry, polarography elemental analysis and FTIR spectroscopy. After Synthesis of metal complex, it was evaluated it for antibacterial and antifungal activities against various pathogenic microorganisms such as; Streptococcus aureus, Proteus. M., klebsiella pneumonia and Asperginus niger, Nigrosporan S.P. B16-F10 melanoma cell and C-57BL/6 mice has been used for anticancer screening of metal complex for in vitro and in vivo study. The result of pharmacological studies with M: L revealed that the complex is more potent as compared to the pure drug as regards to its anticancer activity

Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning

Influence of thyroid secretion on the in­duction of leukemia in Dba mice by methylcholanthrene

1) The influence of thyroid secretion upon the induction of leukemia in Dba/2 male mice by methylcholanthrene was investigated. Radiothyroidectomy significantly reduced the incidence of leukemia in these mice. This reduction in incidence did not occur if radiothyroidectomy was performed after the administration of the carcinogen. 2) Data indicated that hypothyroidism following radiothyroidectomy interfered with the initiation rather than the promotion of methylcholanthrene- induced-Ieukemogenesis. 3) No correlation between incidence of leukemia and body weights in the mice was noted.</p

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

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

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

Endocrine Disorders as a Contributory Factor to Neoplasia in SJL/J Mice

We studied the endocrine status of SJL/J mice. Light and electron microscopy revealed that the adenohypophyses of both sexes became progressively infiltrated with an abnormal number of gonadotropinproducing cells that probably secreted large amounts of luteotropic hormone. The ovaries had numerous large corpora lutea even in animals over 1 year of age with reticulum cell neoplasms. The adrenal cortexes of female mice showed no regression of the reticular zone. In accordance with the anomalous condition of the adenohypophysis and ovary, females had abnormal estrous cycles, with prolonged diestrus and consequent reduction in fertility. These data were discussed in the context of hormone environment versus onset of systemic neoplastic disease and the relationship between hormone dependence and leukemic virus expressio