Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats.

Neuropathic pain is treated using serotonin norepinephrine reuptake inhibitors with mixed results. Pain facilitation mediated by α1-adrenoceptors may be involved, but whether norepinephrine (NE) is tonically released is unclear. The aim of this study was to determine whether NE is tonically released from A7 cells following chronic constriction injury (CCI), and if the lateral hypothalamus (LH) plays a role in this release in male and female rats with nociceptive and neuropathic pain types. Neuropathic groups received left CCI while nociceptive groups remained naïve to injury. Fourteen days later, rats were given intrathecal infusion of either the α1-adrenoceptor antagonist WB4101, the α2-adrenoceptor antagonist yohimbine (74 µg), or normal saline for control. Paw withdrawal latency (PWL) from a thermal stimulus was measured. The generalized estimated equation method was used for statistical analysis. Nociceptive rats given WB4101 had a PWL significantly longer than saline control (7.89 ± 0.63 vs. 5.87 ± 0.52 s), while the PWL of neuropathic rats given WB4101 was 13.20 ± 0.52 s compared to 6.78 ± 0.52 s for the saline control rats. Yohimbine had no significant effect. Microinjection of cobalt chloride (CoCl) in the A7 catecholamine cell group to prevent synaptic transmission blocked the effect of WB4101 in all groups, supporting the notion that spinally descending A7 cells tonically release NE that contributes to α1-mediated nociceptive facilitation. Microinjection of CoCl into the left LH blocked the effect of WB4101 in nociceptive and neuropathic male rats, but had no effect in female rats of either pain type, suggesting differential innervation. These findings indicate that tonic release of NE acts at pronociceptive α1-adrenoceptors, that this effect is greater in rats with nerve damage, and that, while NE comes primarily from the A7 cell group, LH innervation of the A7 cell group is different between the sexes.

Determinants of help-seeking behaviour in cases of epilepsy attending a teaching hospital in India: an indigenous explanatory model.

Psychosocial factors determining the choice of health facility in 30 cases of epilepsy attending the psychiatric outpatient department (OPD) of a teaching (referral) hospital in India were studied. The majority of those who chose indigenous healers as their first contact treatment facility did so on the decision of the family. A belief in the supernatural causation of epilepsy combined with family decision was associated with the choice of indigenous health facility. Belief in the physical cause of epilepsy and the participation of social network in decision making were, on the other hand, closely associated with the choice of practitioners of modern medicine. The time-lag between onset of illness and first contact for treatment was short when indigenous healers were consulted first, however these patients usually took a long time to reach the referral centre when they passed through the indigenous healers.

Evaluation of pan masala for toxic effects on liver and other organs.

The acute and chronic oral toxicity of pan masala (betel quid without betel leaf) was assessed in gavage studies in rats. Clinical parameters (liver and serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase and alkaline phosphatase) and organ weights were measured. The results indicate that chronic feeding of pan masala impaired liver function, as indicated by changes in enzyme activity, and decreased relative weights of the gonads and brain.

Effect of 'Pan Masala' on the germ cells of male mice.

Cytogenetic analyses of meiotic metaphase I germ cells and abnormalities of head morphology of caudal sperms were conducted in male mice following oral feeding of Pan Masala. The substance was ground to a fine powder, dispersed in polysorbate solution and administered via gavage to the animals at 84, 420 and 840 mg/kg body weight at the rate of 10 ml/kg body weight. Polysorbate and cyclophosphamide served as the vehicle control and positive control respectively. The two higher doses, 420 and 840 mg, gave a significant increase in the frequency of X-Y univalents and breaks over those of the vehicle control. Frequency of sperm head abnormalities were significantly high for all the doses tested. The results indicate that Pan Masala is a potent clastogen, reaches the testes and affects the germinal cells.

Chemotherapy drug dose alteration due to radiation therapy in an adjuvant situation in breast cancer.

Fifty-six patients with T1-T3 and T2-T3 N0 medial lesions of breast carcinoma were randomized after modified radical mastectomy to receive either cytoxan, methotrexate, 5-fluorouracil (5-Fu) (CMF) chemotherapy for 1 year (group A) or CMF for 1 year and postoperative radiation therapy (group B). Thirty-two patients received chemotherapy alone and 25 patients received both chemotherapy and radiation therapy. Twenty-five of 32 group A patients (median age 52) and 20/24 group B patients (median age 50) were evaluable. Leukopenia was the major cause of drug dose reduction in both groups. In group A, 4/25 patients (16%) had leukopenia at less than the 2500 level, whereas 8/20 (40%) group B patients had leukopenia at the same level. If 70% of all three drug dosages are considered as adequate chemotherapy, 21/25 (84%) patients received adequate chemotherapy in group A, and 10/20 (50%) in group B (p approximately equal to 0.029 from contingency table). It appears that radiation therapy in postmastectomy patients hinders adequate drug dose delivery in an adjuvant setting.