Effect of carbimazole induced hypothyroidism and thyroxine replacement on the growth of the long bones in albino rats of different age groups.

To evaluate the effect of carbimazole induced hypothyroidism and thyroxine replacement, on the growth of long bones of albino rats of different age groups. Experimental albino rats were developed with carbimazole and carbimazole plus thyroxine for a period of six weeks. At the end of the experiment the animals were sacrificed, fixed and processed to demonstrate the bony and cartilaginous parts. The ulna and tibia of both sides were measured for intact bone length & diameter and the data compared. The reduction in length and circumference observed, at the end of experiment, in ulna was 10.89%, & 11.94% and in tibia it was 12.52%, 14.81% in carbimazole treated group respectively, while in carbimazole plus thyroxin treated group the reduction in length & circumference of ulna was 1.37% & 1.88% and in tibia it was 1.86% & 3.08% respectively. They were compared to their age matched controls. The reduction in length and circumference in ulna was 5.58% & 6.25% and 6.42% and 5.88% in tibia respectively among the carbimazole treated animals while in the carbimazole plus thyroxine treated animals the reduction was only 0.63% and 3.12% in ulna and 0.91% and 1.06% in tibia respectively. The results show that hypothyroidism and its replacement therapy affects the endochondral as well as periosteal bone growth and results in reduction in length as well as circumference of long bones.

Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson's disease induced by the Japanese encephalitis virus.

A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor, significantly increased norepinephrine and 5-hydroxytryptamine concentrations in the rat brain and also significantly increased acetylcholine and dopamine (DA) levels in the rat striatum. Urinary isatin concentrations in patients with Parkinson's disease tend to increase according to the severity of disease. We have developed a rat model of Parkinson's disease induced by the Japanese encephalitis virus (JEV). The distribution of the pathological lesions of JEV-rats resemble those found in Parkinson's disease. Significant behavioral improvement was observed in JEV-rats after isatin, L-DOPA and selegiline administration using a pole test. Both isatin and selegiline prevented the decrease in striatum DA levels of JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not selegiline. These findings suggest that JEV-infected rats may serve as a model of Parkinson's disease and that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Impact of selenium, iron, copper and zinc in on/off Parkinson's patients on L-dopa therapy.

We have quantitated CSF and serum levels of Selenium, iron, copper and zinc by Atomic absorption spectrophotometer in 36 patients with parkinson's disease all on L-dopa therapy. Out of these 19 showed on or positive response to L-dopa where as 21 patients showed on and off response. These data were compared with 21 healthy controls. The results showed that serum levels of iron, copper and zinc remained unchanged where as in CSF, significant decrease in zinc was found in both on and on/off PD patients indicating the deficiency of zinc which continues in the worsening clinical condition of off patients. The level of copper remained unchanged in both on and on/off PD patients. Iron and selenium increase in CSF of both patients which is a clear evidence of relationship between increased iron and selenium level in brain which could be correlated with decrease in dopamine levels and oxidative stress in PD Patients.

Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus.

We previously reported that exogenously administered isatin, an endogenous monoamine oxidase (MAO) inhibitor, significantly increased acetylcholine (ACh) and dopamine (DA) levels in the rat striatum. Selegiline [(-)-deprenil] was developed as a MAO-B inhibitor more than 30 years ago and widely used in the treatment of Parkinson's disease. Effects of isatin or selegiline were investigated in Japanese encephalitis virus (JEV)-induced post-encephalitic parkinsonism rats by a pole test for detecting motor activity and by the determination of biogenic amine levels. Motor activity of JEV-induced rats receiving isatin (100 mg/kg per day for 1 week, i.p.) or selegiline (0.2 mg/kg per day for 1 week, i.p.) was significantly improved compared with that of untreated JEV-infected rats. Both isatin and selegiline prevented the decrease in striatal DA levels in JEV-rats. The increased turnover of DA (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not by selegiline. These results suggested that exogenously administered isatin and selegiline can improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

Nitric oxide and neuronal and pancreatic beta cell death.

Neural cells are found in all organs of the body and play an important role in the maintenance of the internal milieu. The pancreatic beta cell is the most numerous cell types in the endocrine pancreas. It is particularly important because of its role in insulin secretion, a crucial hormone in glucose metabolism. In view of this, the significance of the survival of neural and pancreatic beta cell cannot be over emphasised. Neural and pancreatic beta cell death occurs in a variety of ways. The destruction of neural cells can be induced with (1) free radicals (H(2)O(2), O(2)(-)(,) HO(-)) and nitric oxide; (2) Cytokines (tumour necrosis factor, interleukin-1 beta, interferon-gamma); (3) Glutamate; (4) Amphetamine analog (Ecstasy); (5) S100 protein; (6) Ammonia; (7) Iron ions; (8) Resins, e.g. methylmethycrylate. Pancreatic beta cell can be destroyed by (1) free radicals (H(2)O(2), O(2)(-)(,) HO(-)) and nitric oxide; (2) Cytokines (tumour necrosis factor, interleukin-1 beta, interferon-gamma); (3) alkylating agents (streptozotocin, alloxan, N-methyl-nitrosourea N-ethyl-N-nitrosourea, Methylmethanesulphonate and ethylmethanesulphonate); (4) hyperglycaemia; (5) islet amyloid poplypeptide; and (6) Inositol Monophosphate dehydrogenase inhibitors. There is enough evidence that most of these agents involved in neural and pancreatic beta cell death exert their toxic effects through the nitric oxide pathway. Neuroprotective agents include vitamin B12 analogs and alpha-tocopherol, NOS inhibitors, antioxidants (e.g. glutathione, superoxide dismutase), metals like cobalt, neurotrophic receptors (Akt kinase) and growth factors. The pancreatic beta cell death induced by these toxic agents can be prevented and or delayed by nicotinamide (vitamin B3), heat shock, copper, alpha-tocopherol (vitamin E), succinic acid, dihydroxylipoic acid, fusidic acid, glucocorticoids, cyclosporin A, growth factors and gene therapy.

Cell death induced by MPTP, a substrate for monoamine oxidase B.

MPTP is known to cause PD symptoms in primates and in rodents. In order to exert its neurotoxicity MPTP must be converted by monoamine oxidase B into MPP(+) which is the true toxic agent. MPP(+) is taken up by the dopaminergic neurons of the substantia nigra in which it induces cell death. The present work reviews and discusses papers in which specific methods were used to determine whether cell death induced by MPTP/MPP(+) should be considered as apoptosis or necrosis. These two cell death modes may be distinguished using morphological and biochemical criteria. The effect of MPTP/MPP(+) was studied in vitro and in vivo. The results show that no univocal answer is possible. The most widespread interpretation is that MPTP/MPP(+) causes apoptosis when its neurotoxic effect is only sligh and necrosis when it is stronger. Similar considerations may be made also concerning the type of cell death occurring in the dopaminergic neurons in the substantia nigra of PD patients.

Neurochemistry and neuropharmacology of emesis - the role of serotonin.

Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex which is integrated in the medulla oblongata. Emesis caused by cytotoxic drugs and radiation is associated with an increase in the concentration of 5-hydroxytryptamine (5-HT) in the intestinal mucosa and in the brainstem. 5-HT released from enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT(3) receptors on the adjacent vagal afferent nerves. This vagal afferent nerve depolarization may evoke the vomiting reflex. This review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release from EC cells and afferent vagus nerve activity.

Variation in cerebrospinal fluid levels of neuropeptide Y, cholecystokinin and substance P in patients with neurological disorders.

Neuropeptide Y, cholecystokinin (tetra- and octasulphated peptides) and substance P were measured in lumbar cerebrospinal fluid obtained from patients with various neurologic disorders such as Parkinson's disease, cerebrovascular disorders, multiple sclerosis, tuberculous meningitis and aseptic meningitis. These results are statistically compared with healthy results. The results accumulated showed that the data collected can provide the vital information necessary for designing drug therapy.

Distribution of serotonin and its effect on insulin and glucagon secretion in normal and diabetic pancreatic tissues in rat.

OBJECTIVES: The distribution of serotonin (5-HT) and its effect on insulin and glucagon secretion were investigated to examine whether there are changes in the pattern of distribution and effect of 5-HT after the onset of experimental diabetes. METHODS: The pattern of 5-HT and its effect of insulin and glucagon secretion was examined using immunohistochemical and radioimmunoassay techniques, respectively. RESULTS: 5-HT was demonstrated mainly in the neural elements of the pancreas. 5-HT-containing fine varicose nerve fibers were discerned in the wall of blood vessels and pancreatic ducts. 5-HT-containing nerves were also observed in the periacinar and periinsular regions of normal pancreas. The pattern or intensity of the distribution of serotonergic nerves did not change after the onset of diabetes. The perivascular, periductal, periacinar and periinsular regions of diabetic pancreas all contained 5-HT positive nerves. 5-HT elicited marked increases in insulin secretion from normal pancreas but had an inhibitory effect on insulin secretion from diabetic pancreatic tissues. In contrast, 5HT inhibited glucagon secretion from normal pancreatic tissue fragments but stimulated glucagon release from diabetic pancreatic tissue fragments. conclusion: 5-HT is well distributed in normal and diabetic pancreatic tissues and has stimulatory effects on insulin secretion from normal pancreas and glucagon secretion from diabetic pancreas. This result indicates that although 5-HT may help in the maintenance of the blood sugar level in normal pancreas by increasing insulin secretion and decreasing glucagon secretion, it may also aggravate the hyperglycemia observed in diabetes mellitus and hence exacerbate the symptoms of hyperglycemia in poorly controlled diabetes mellitus.

The neurochemical markers in cerebrospinal fluid to differentiate between aseptic and tuberculous meningitis.

In this study, the use of neurochemical markers in patients with aseptic and tuberculous meningitis has been investigated. The cerebrospinal fluid levels of amino acids, nitrite (a metabolite of nitric oxide), vitamin B12 and homocysteine were quantitated in both groups of patients. Among the amino acids, aspartic acid and glutamic acid both excitatory amino acid, GABA, glycine and tryptophan were all significantly increased in both patient groups whereas decreased level of taurine and increased level of phenylalanine were only found in patients with tuberculous meningitis. The levels of nitrite and its precursor arginine were significantly higher in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. A significantly increased homocysteine level and a decreased level of vitamin B12 were found only in patients with tuberculous meningitis whereas unchanged levels were found in patients with aseptic meningitis. This indicates that patients with tuberculous meningitis are particularly prone to vitamin B12 deficiency resulting into increased level of HC, and involvement of free radical showing the importance of these biological markers for promoting the possibility for the design of therapeutic approach.

Variation in activity of monoamine metabolizing enzymes in rat liver during pregnancy.

1. Catechol-0-methyltransferase (COMT) and monoamine oxidase (MAO) activities in rat liver were measured during pregnancy, parturition and postpartum. Compared with activity in non-pregnant controls, both enzymes showed a significant decrease in activity which was most pronounced at day 18. 2. The metabolism of intravenously infused [3H]-adrenaline to [3H]-metanephrine and to [3H]-acidic metabolites was also significantly depressed during pregnancy but had returned to control values by the 21st day. 3. The effects of reserpine and/or nialamide on hepatic COMT and MAO were studied in control and 20-day-pregnant rats. Their action on COMT activity differed in the two groups. MAO was inhibited to a similar extent in these groups whether the drugs were given separately or in combination. 4. It seems possible that the changes in endocrine function which occur during pregnancy are responsible for the observed alterations in enzyme activity.