Activation of striatal dopamine receptors induces pain inhibition in rats

Summary In the rat, elevating dopamine content in corpus striatum with electrical stimulation of substantia nigra or direct administration of apomorphine (50–200g) into the lateral cerebral ventricle or apomorphine (2–10g) into the caudate-putamen complex decreased pain sensitivity (as shown by an increase in the latency to hind-paw lick in the hot plate test). Furthermore, the decreased pain sensitivity after the central administration of apomorphine was antagonized by pretreatment with haloperidol (a dopamine antagonist). On the other hand, lowering dopamine content in corpus striatum with electrolytic destruction of substantia nigra and 6-hydroxydopamine lesions to the substantia nigra, as well as direct injection of haloperidol into the lateral cerebral ventricle or caudate-putamen complex increased pain sensitivity. The data indicate that activation of striatal dopamine receptors in rat brain induces pain inhibition.     

Effects of adenosine 3′, 5′-cyclic monophosphate on thermoregulation in both rats and rabbits

Summary The effects of intraventricular administration of dibutyryl adenosine 3, 5-cyclic monophosphate (db cyclic AMP) on the thermoregulatory responses of unanesthetized rats and rabbits to different ambient temperatures (T_a) were assessed. Administration of db cyclic AMP (10–60 mM) produced dose-dependent hypothermia in both rats and rabbits at T_a 2–22 °C. The hypothermia in response to db cyclic AMP was due to decreased metabolic heat production and cutaneous vasodilatation. There was no change in respiratory evaporative heat loss. In contrast, in the heat (30–32 °C), db cyclic AMP administration produced dose-dependent hyperthermia in these animals. The hyperthermia was due to increased metabolism (due to muscular shivering) and decreased heat losses. The reduction in heat losses was shown by a decrease in both cutaneous circulation and respiratory evaporative heat loss. The data demonstrate that the thermoregulatory responses induced by central administration of db cyclic AMP are T_a-dependent.     

Modification of vascular response to synthetic oxytocin by oestrogen in rabbit

Intravenously administered oxytocin caused a dose-related fall in blood pressure of the rabbit. When oxytocin was administered in oestrogen-primed animals, the depressor response was converted to a pressor one "Oxytocin reversal". The "oxytocin reversal." was abolished after treatment with dihydroergotamine, hexamethonium or adrenalectomy. The "oxytocin reversal" did not appear in reserpinized animals.     

Concurrent cisplatin and radiotherapy in advanced head and neck cancer

Management of Head and Neck Cancers poses a challenge inspite of several advances because of poor success in terms of response rate, survival and reduced morbidity of the patients. In the present study 30 untreated histologically proven cases of head and neck cancers were subjected to weekly radiotherapy with adjuvant chemotherapy (cisplatin 30 mg/m² intravenously). This study group was compared with a group of 30 patients who were given only radiotherapy. Results have shown that combination of chemotherapy with radiotherapy gives a significantly better results in tumour as well as nodal response with minimal toxicities.     

Tissue repair plays pivotal role in final outcome of liver injury following chloroform and allyl alcohol binary mixture.

The objective of this study was to evaluate the interaction profile of chloroform (CHCl(3))+allyl alcohol (AA) binary mixture (BM)-induced acute hepatotoxic response. Plasma alanine aminotransferase (ALT) was measured to assess liver injury, and 3H-thymidine (3H-T) incorporation into hepatonuclear DNA was measured as an index of liver regeneration over a time course of 0-72 h. Male Sprague-Dawley (S-D) rats received single ip injection of 5-fold dose range of CHCl(3) (74, 185 and 370 mg/kg) in corn oil (maximum 0.5 ml/kg) and 7-fold dose range of AA (5, 20 and 35 mg/kg) in distilled water simultaneously. The doses for BM were selected from individual toxicity studies of CHCl(3) alone [Int. J. Toxicol. 22 (2003) 25], and AA alone [Reg. Pharmacol. Toxicol. 19 (1999) 165]. Since the highest dose of each treatment (CHCl(3)- 740 and AA- 50 mg/kg) yielded mortality due to the suppressed tissue repair followed by liver failure, this dose was omitted for BM. The levels of CHCl(3) (30-360 min) and AA (5-60 min) were quantified in blood and liver by gas chromatography (GC). The liver injury was more than additive after BM compared to CHCl(3) alone or AA alone at highest dose combination (370+35 mg/kg), which peaked at 24 h. The augmented liver injury observed with BM was consistent with the quantitation data. Though the liver injury was higher, the greater stimulation of tissue repair kept injury from progressing, and rescued the rats from hepatic failure and death. At lower dose combinations, the liver injury was no more than additive. Results of the present study suggest that liver tissue repair, in which liver tissue lost to injury is promptly replaced, plays a pivotal role in the final outcome of liver injury after exposure to BM of CHCl(3) and AA.     

Type 1 diabetic mice are protected from acetaminophen hepatotoxicity.

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.     

Depression in women--issues in evaluation and management

Depression is probably the most common psychiatric disorder in women. Women are a vulnerable group of depression due to psychological, social and biological factors. Marital relationships, social support, roles and self esteem are factors that contribute to depression. In addition, several periods in women's life relating to the reproductive cycle are periods of increased vulnerability. Management of depression in women should consist of detailed assessment of all the above factors. Drug treatment of depression in women requires an in depth understanding of pharmacokinetics of the drugs used and possible drug interactions. Treatment of depression in women should integrate both psychosocial and biological treatment modalities.     

Effects of irradiation on nasal mucociliary clearance in head and neck cancer patients

A prospective longitudinal study was conducted on fifty patients of histopathologically confirmed head and neck cancer with the main aim to assess the nasal mucociliary clearance, pre-and post-irradiation; and to compare the findings with the healthy non-irradiated age and sex-matched controls. All the patients underwent saccharin particle test for nasal mucociliary clearance before commencement of radiation therapy and again within 6 months of completion of radiation therapy. The difference between the saccharin perception times of nasal mucosa in the healthy non-irradiated controls and the pre-irradiated head and neck cancer patients were statistically inssignificant (P>0.05). But, the difference between the saccharin perception times of nasal mucosa in the pre-and post-irradiated head and neck cancer patients was found to be statistically significant (P=0). It is concluded that even indirect irradiation of nasal mucosa in head and neck cancer patients significantly affect its ciliary activity. Significance of total radiation dosage along with chemotherapy in some cases was also studied.     

Supravital staining: It's role in detecting early malignancies

The efficacy of supravital staining in the detection of malignancies in oro and oropharyngeal lesions and its role in the detection of malignant changes in premalignant lesions were studied. This prospective study comprises 90 cases of clinically suspicious lesions and it was done over a period of 3 years. Most of the patients had multiple risk factors for the development of malignancy. All underwent staining with a modified solution of 1% toluidine blue (TB). In our study the overall sensitivity was 97.29% and the specificity was 62.5%.