Orexins have been implicated in several biological functions, such as food and water intake. This study examined the pattern of distribution of orexin-1 receptor (OX1R) in the pancreas of normal and diabetic rats. Diabetes mellitus (DM) was induced by streptozotocin (STZ). Four weeks after the induction of DM, the pancreases of normal and diabetic rats were processed for immunohistochemistry. OX1R-positive cells were observed in the periphery of pancreatic islets of normal and in both the peripheral and central regions of the islet of diabetic rats. The number of OX1R-positive cells in the islets increased significantly (p < 0.0001) after the onset of diabetes. Moreover, ganglion cells and the periductal and interlobular nerve fibres of the exocrine pancreas also expressed OX1R. In conclusion, OX1R may play a role in the initiation of increased food intake via pancreatic hormones.

It is well established that the phosphorylation of tyrosine hydroxylase (TH) at Ser40 is critical in regulating the catalytic activity of the enzyme. However, the influence of the phosphorylation of Ser40 on the stability of TH protein has not been investigated. This study was performed to estimate such a possibility. Although the treatment of rat pheochromocytoma cell line PC12 cells with forskolin increased the amount of TH phosphorylated at Ser40 in the cells, it did not affect the total amount of TH in the cells. Next, human TH type 1 (hTH1) of wild-type and a mutant missing the first 52 amino acid residues were expressed as histidine-tagged forms in PC-12 cells, and then the cells were treated with forskolin. However, the phosphorylation of hTH1 at Ser40 did not affect the amount of the wild-type hTH1 protein present in PC12 cells. Finally, wild-type and a mutant in which Ser40 was replaced by Asp (S40D, a mimic of TH phosphorylated at Ser40) were expressed in PC-12 cells as histidine-tagged forms or untagged forms. Neither histidine-tagged nor untagged forms showed any difference in their amounts of wild-type hTH1 and S40D hTH1 present in the cells. Collectively, these results indicate the fact that the phosphorylation of Ser40 does not affect the stability of TH protein in PC12 cells.

Nigella sativa (NS), an endogenous plant of family Ranunculaceae, exhibits a wide range of biological activity. This report explores the effect of aqueous extract of NS seeds on penicillin-(PCN-100 IU in 100 μl) induced epileptic rat model. Oral pretreatment of NS (250 mg/kg) suppressed PCN-induced seizure considerably, reduced spike-wave discharges and occurrence of generalized tonic–clonic seizures. Electroencephalographic data showed NS pretreatment to experimental animals elicited 85% abolition of high voltage spike discharges. NS pretreatment resulted in elevation of serotonin (5-HT) level and decreased dopamine (DA) level in cerebral cortex (CC), cerebellum (CB), caudate nucleus (CN) and midbrain (MB). A significant decrease in norepinephrine (NE) level was observed only in the CC. The present study suggests that chronic administration of NS protects PCN-induced generalized epilepsy by selectively altering the monoamine level in different brain regions. The seizure abolition observed in the NS pretreated rats was comparable to the anticonvulsive pattern exhibited by diazepam. The results suggest that NS has promising anticonvulsant action.

The effect of aqueous extract of garlic (AEG) on triton WR 1339 induced hypercholesterolemia and hypertriglyceridemia has been studied in rats. A single injection of triton WR 1339 produced a significant increase in serum cholesterol and triglyceride (p < 0.001). The weight and total lipid of the livers of the triton treated rats were significantly increased (p < 0.001). AEG was extracted from chopped garlic pieces on which previously an exhaustive extraction had been made with petroleum ether, ethyl acetate and ethyl alcohol until no odour remained in them. The AEG so prepared had a significant effect on lowering the triton induced cholesterol (p < 0.001) and triglyceride (p < 0.001) in the blood. AEG showed a significant hypocholesterolemic and hypotriglyceridemic effect. These activities were higher than the reference compound nicotinamide, a well known hypocholesterolemic and hypotriglyceridemic molecule. Studies on the liver treated with AEG showed that the weight remained unperturbed but triglyceride was significantly lowered. However, some possible lipid content disturbances in the liver were suggested on the basis of data from the treated livers. It is therefore, inferred that AEG may contains hypocholesterolemic and hypotriglyceridemic components other than that already known. It is encouraging that the non-odorous character of AEG containing specific ingredient has a potential for use in lowering blood lipids.

From Volume 20 (2006), this title is published by Society of Integrated Sciences (International Medart, PO Box 37, 814 99 Bratislava 1, Slovak Republic, E-mail: publisher@nel.edu, Fax: +41 13553207).

It has been reported that corticotropin-releasing factor (CRF) is involved in the regulation of norepinephrine neuron responses to stress such as an immobilized stress. Furthermore, systemic lipopolysaccharide (LPS) injection upregulates the transcription of the genes encoding CRF and CRF type 1 receptor in the paraventricular nucleus of the hypothalamus. We have already reported that an increase in norepinephrine turnover within the murine locus coeruleus is accompanied by septic shock triggered by LPS intraperitoneal injection. We also elucidated that the expression levels of the enzymes involved in the catecholamine biosynthesis were altered by peripheral LPS injection. Collectively, the effects of CRF on the expression levels of the enzymes at murine locus coeruleus were investigated by peripherally injecting CP-154,526, a CRF receptor type 1 antagonist. Pretreatment with CP-154,526 attenuated the increase in expression levels of GTP cyclohydrolase I mRNA due to intraperitoneal LPS injection at 4 h after the injection. However, no effects on the expression level of tyrosine hydroxylase mRNA at the site were observed. Taken together with the fact that LPS injection enhances tetrahydrobiopterin biosynthesis at locus coeruleus, CP-154,526 may attenuate the increase of NE turnover by suppressing the enhanced GCH expression level at the site caused by peripheral LPS injection.

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and to have little or no predictive value or application to human medicine. We briefly discuss the reasons why this may be so, reflect upon the consequences for future medical progress and, on the basis of our findings, suggest a more scientifically robust and promising way forward.

Transgenic Tg8 mice provide an experimental model of selective lack of the gene encoding monoamine oxidase A (MAO A), and correspond to analogous human genetic pathology found in a Dutch family. To investigate the possible consequences of the effect of the lack of a major enzyme in serotonin and catecholamine metabolism on cognitive functions, MAO A-deficient mice were subjected to a passive avoidance task. Significant differences in the learning ability and in the retention of passive avoidance response between Tg8 mice and the wild-type mice C3H/HeJ were found. MAO A-deficient mice demonstrated increased step-through latency and a longer retention of memory trace for 11 experimental days as compared to wild-type mice. We found that Tg8 mice are more resistant to detention-induced amnesia and show better social memory in social recognition test than C3H mice. The findings show an enhancement of learning and memory retention in the MAO A-deficient mice.

We have quantified levels of iron, copper and zinc in cerebrospinal fluid (CSF) and serum by atomic absorption spectrophotometer in 36 patients with Parkinson's disease (PD), all on L-dopa therapy. Out of these 36, 17 showed On or positive response to L-dopa whereas 19 patients showed On and Off response. These data were compared with 21 healthy controls. The results showed that serum levels of iron, copper as well zinc remained unchanged whereas in CSF, a significant decrease in zinc was found in both On and On/Off PD patients, indicating the deficiency of zinc which continues in the detoriating clinical condition of Off patients. The level of copper remained unchanged in both On and On/Off PD patients. Iron increases in CSF of both patients, which is clear evidence of a relationship between increased iron level in brain that could be corrolated with decrease in dopamine levels and oxidative stress in PD Patients.