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.     

Telemedice in otolaryngology (An Indian Perspective)

Telemedicine is an upcoming concept in the modem world, It needs to be inculcated to improve the coordination amongst the health care providers in order, not only to update themselves but also to provide a coordinated approach far eatering masses in a developing country The various advantages and drawbacks are highlighted, and stress is made on starting a remote method of tetecommunication amongst us.     

Pharmacokinetics, in-situ absorption and protein binding studies of a new neuroleptic agent centbutindole in rats.

The present study reports the absorption kinetics, plasma protein binding and pharmacokinetic profile of the centbutindole (I) after i.v. and oral dosing in rats. In addition, an in-situ absorption study was carried out using a closed-loop technique at pH 2.6 and 7.4. The rate of absorption at pH 2.6 was 5-fold less compared to that observed at pH 7.4. In-vitro and in-vivo protein binding (ultra filtration technique) was independent of substrate concentration over a range of 1.25-10.0 microg/ml. Pharmacokinetic parameters of I were determined in male rats after administering a single 4 mg/kg oral dose and 2 mg/kg intravenous dose. The peak serum concentration of I was found to be 50.1 ng/ml at 30 min after oral administration followed by a secondary Cmax of 43.2 ng/ml at 180 min. For the hydroxy metabolite (II), a Cmax of 6.4 ng/ml was measured at 360 min after oral administration of I. After oral dosing an irregular concentration-time profile with secondary peaks was observed for both I and II. The terminal half-lives for I and II after oral dosing were 163 and 263 min, respectively. After intravenous dosing, the levels of I decreased biexponentially with a distribution (t(1/2) alpha) and elimination (t(1/2) beta) half-lives of 5.7 and 128 min, respectively. Comparison of the AUC after oral and intravenous dosing of I indicates that only about 24% of the oral dose reaches the systemic circulation. The limited bioavailability can either be due to the poor solubility of the compound and/or extensive first pass metabolism in the gastrointestinal (GI) tract. Co-administration of polyethylene glycol (PEG) at oral dosing improves solubilization and increases bioavailability.     

A farnesyltransferase inhibitor increases survival of mice with very advanced stage acute lymphoblastic leukemia/lymphoma caused by P190 Bcr/Abl.

Treatment of chronic myelogenous leukemia with a specific inhibitor of the Bcr/Abl tyrosine kinase, imatinib, has shown great promise. However, acute lymphoblastic leukemias that express Bcr/Abl only transiently respond to imatinib. Therefore, alternative treatments for this type of leukemia are urgently needed. Here, we examined the activity of the farnesyltransferase inhibitor SCH66336 as a single chemotherapeutic agent in a nude mouse model representative of very advanced stage Bcr/Abl P190-positive lymphoblastic leukemia/lymphoma. Our results show that oral administration of the inhibitor was able to significantly increase the survival of these mice compared to controls treated with vehicle (P<0.005), and caused marked regression of the tumor burden in the treated mice. Upon prolonged treatment, lymphomas re-emerged and a subset of cells from two of such lymphomas tested was able to survive in the presence of increased concentrations of SCH66336. The same cells, however, remained sensitive towards imatinib. A combination of the two drugs, preceded by a therapy to reduce the initial tumor burden, could be very effective in the treatment of Ph-positive ALL. We conclude that SCH66336, on its own, is remarkably effective in eradicating large numbers of lymphoblastic lymphoma cells and causing visible reduction in tumor size, with minimal toxicity.     

Myxoma of maxilla

A case of Myxoma involving left Maxilla, presenting as swelling of left side of face and Oral cavity with bilateral nasal obstruction is reported.     

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.