Modification of apomorphine-induced behaviour following chronic swim exercise in rats.

Four week swim exercise schedule (45 min day-1, 6 days each week) in rats led to a significant adaptive change in functional responsiveness of dopamine receptors (auto-receptors) in the nigrostriatal and mesolimbic system that was evident from the modification of behavioural responses elicited by a low dose of apomorphine, a direct acting dopamine receptor agonist. Thus, a remarkable increase in yawning response, development of full blown stereotypy, as well as profound attenuation of locomotory and hypothermic response was observed in exercise-trained rats as compared with the non-exercise group (control), following intraperitoneal administration of 0.3 mg kg-1 of apomorphine.     

Antagonists that demonstrate species differences in neurokinin-1 receptors.

125I-Bolton-Hunter-substance P (125I-BH-SP) binding properties of three novel classes of neurokinin-1 (NK-1) receptor antagonists were investigated in tissues derived from humans, guinea pigs, and rats. 125I-BH-SP was shown to bind to a single class of binding sites, with similar dissociation constants, Kd, in human astrocytoma cells (U-373 MG), human urinary bladder, guinea pig forebrain, guinea pig ileum longitudinal smooth muscle, rat forebrain, and rat duodenum. In each tissue preparation, known peptide agonists and peptide antagonists yielded potencies typical for a NK-1 receptor profile, with little difference in binding properties between the various tissues. However, when the three classes of compounds, heterosteroids, cyanines, and modified peptides, were tested for their ability to displace 125I-BH-SP binding from the NK-1 receptor, very different binding profiles were observed. The heterosteroids were shown to be as much as 3 orders of magnitude more potent in tissues derived from rats than from humans or guinea pigs. A distinct species-dependent structure-activity relationship (SAR) was also observed for this class of compounds. Like the heterosteroids, the cyanines displaced 125I-BH-SP with 10-30-fold higher affinity in rat tissues than in human and guinea pig tissues. However, the SAR generated by the cyanines was comparable in all tissues studied. The modified peptides, on the other hand, were up to 10-100-fold more potent in human and guinea pig than rat tissues, producing a SAR that differed between the various species. No differences in binding properties between central nervous system and peripheral tissues from the same species were seen with these compounds. These results provide evidence for species differences in NK-1 receptors in humans, guinea pigs, and rats. Because it is known that there exists great sequence identity between rat and human NK-1 receptors, it is hypothesized that key amino acid changes or different lipid environments within the transmembrane binding region of the receptor may account for the observed species difference. Furthermore, this study emphasizes that caution is necessary in the choice of species to be used in development programs targeted towards therapeutic entities in the NK-1 receptor antagonist area.     

Neurogenic bladder in acquired immune deficiency syndrome (AIDS).

This is the first report of incidence of neurogenic bladder in patients with acquired immune deficiency syndrome (AIDS) and emphasizes that it is a significant cause of various voiding dysfunctions in these patients. Neurologic disease occurs in about one third of patients with AIDS. Both central and peripheral nervous systems may be involved. Urodynamic evaluation is necessary for assessment and management of neurogenic voiding disorders in this group of patients.     

Acute polymyositis associated with W. bancrofti

Two cases of acute polymyosotis associated with W. bancrofti , presented with generalised painful swelling and weakness of the muscles. These patients had elevated muscle enzymes, a myopathic EMG pattern, inflammatory myopathy on biopsy and W. bancrofti in the peripheral blood smear. The clinical, improvement of the disorder and total clearance of microfilariae was obtained with the combination therapy of steroid and diethyl-carbamazine in comparison with steroid alone.     

Acute hypercalcemia, pancreatic duct permeability, and pancreatitis in cats

We investigated the effects of hypercalcemia on pancreatic duct permeability and pancreatitis in cats. Acute hypercalcemia was maintained by an infusion of calcium gluconate; controls received saline solution. Chronic hypercalcemia was maintained by diet and by vitamin D and dihydrotachysterol injections. Portal venous blood was analyzed for large dextran molecules that had been perfused through the pancreatic duct. In a separate group of hypercalcemic animals, we perfused the duct with activated pancreatic enzymes to induce acute pancreatitis. After 24 hours of hypercalcemia, dextrans were detected in the portal venous blood of 6 of 11 hypercalcemic and none of the 6 control animals (p less than 0.05). After 12 hours of hypercalcemia, dextrans were detected in all 7 hypercalcemic and 1 of 7 control animals (p less than 0.001). The degree of pancreatic inflammation was greater in the 12-hour animals than in the controls (p less than 0.001). After 14 days of hypercalcemia, however, there were no differences in dextran permeability or pancreatitis in experimental or control animals. Our results indicate that acute hypercalcemia increases the permeability of the pancreatic duct to molecules the size of pancreatic enzymes. This could be important in the pathogenesis of acute pancreatitis associated with hypercalcemic states.     

The effect of TNFa on bradykinin receptor binding, phosphatidylinositol turnover and cell growth in human A431 epidermoid carcinoma cells.

In this study, we examined the effect of TNFa on bradykinin (BK) B2 receptor binding and function in human A431 epidermoid carcinoma cells. [3H]BK binds to a single class of receptors on A431 cells in a saturable and reversible manner. A binding affinity (KD) of 3.0 +/- 0.3 nM (n = 4) and a Bmax of 151 +/- 14 fmols/10(6) cells, representing approximately 90,000 BK receptors per cell, was observed. The rank order of potency for BK agonist peptides indicates that the A431 BK receptor appears to be of the B2 subtype. When A431 cells were incubated with TNFa (10 ng/ml) for 48 h prior to BK binding, a significant decrease in the number of BK receptors compared to control was observed. TNFa did not influence the affinity of BK binding to A431 cells and direct addition of TNFa to the binding assay did not effect BK binding. BK-stimulated IP1 formation appeared to be increased in TNFa treated cells compared to control whereas histamine-stimulated IP1 formation was not influenced. Both control and TNFa treated cells were greater than 95% viable. However, TNFa treated cells were blocked in the G1 phase of the cell cycle resulting in a decrease in DNA synthesis. This may be one mechanism for the TNFa-induced decrease in BK receptors in A431 cells.     

Effect of long-term use of Norplant implants on haemostatic function.

This study describes the effects of Norplant on haemostatic function after 5 years of use in 97 women. There was a decrease in vitamin-K dependent Factors II, V, VII and reduction in fibrinolytic activity at 2 and 4 years of use. Increased platelet numbers and accelerated platelet aggregation were found throughout the 5 years of Norplant use, whilst raised alpha 2-Macroglobulin (a2-M) and antithrombin III (ATIII) antigen level were observed for up to 4 years of use. Prolonged Norplant use does not appear to activate the coagulation system and does not enhance a state of hypercoagulation.     

Shape of the myopic eye as seen with high-resolution magnetic resonance imaging.

We have obtained multislice magnetic resonance (MR) images of the eye and calculated ocular dimensions along the three cardinal axes: antero-posterior (A-P), equatorial, and vertical. We found no difference in the shape of hyperopic (average refractive error: +3.72 D) and emmetropic eyes, both of which had an equatorial diameter longer than the A-P and vertical diameters. Myopic eyes (average refractive error: -6.54 D) were larger than hyperopic eyes, and most had the same spheroelliptical shape as that of the emmetropic and hyperopic eyes. The results suggest that during myopic progression an overall enlargement or a radial volume expansion has occurred.