Role of preoperative chemotherapy in squamous cell carcinoma of esophagus in kashmir, a cancer belt - a pilot study.

BACKGROUND: Esophageal carcinoma is the fifth leading gastrointestinal malignancy and is one of the leading causes of cancer related death. Despite improvements in surgical technique over the last few decades, the outcome has been dismal, with overall 5 year survival not exceeding 15%-25%. AIMS AND OBJECTIVES: To evaluate the effect of preoperative chemotherapy on resectability, complication rate and overall survival in patients with squamous cell carcinoma esophagus. MATERIALS AND METHODS: 50 patients with histologically confirmed squamous cell carcinoma (SCC), with localised or loco-regional disease (stage 4 excluded) were divided into 2 groups. Group A patients were subjected to 2-3 cycles of pre-operative chemotherapy (5FU-CDDP), whereas Group B patients were directly operated on. OBSERVATIONS: 3 (12%) patients in group A showed complete pathological response to chemotherapy and 18 (72%) showed a partial response, with four patients (16%) showing resistance to chemotherapy. There was no statistically significant difference in terms of response to chemotherapy with respect to degree of differentiation of tumor. There was no significant difference in the overall resectability rates between the two groups (p > 0.05), but R0 resection was achieved in 20 (80%) of group A and only 10 (40%) of group B, the difference being statistically significant (p < 0.05). The rate of overall complications was also much higher in the control group. Initially there was no significant difference in the survival between the two groups, but later (20 months) the study group showed a slight non-significant advantage. CONCLUSION: Preoperative chemotherapy significantly increases the rate of R0 resection without significantly increasing postoperative morbidity and mortality in patients with squamous cell carcinoma of esophagus. However, to assess the impact on survival the study period needs to be extended.

Actions of some flavonoids on specific and non-specific immune mechanisms.

The immunomodulatory activity of some flavonoids on antigen specific humoral and cell mediated immune responses and complement-mediated hemolysis has been investigated and compared with that of levamisole. Flavanone, 6-methoxyflavanone, 7-methoxyflavanone and bavachinin enhanced the sheep erythrocyte (SRBC), induced primary and secondary humoral immune responses in mice, and 6-hydroxyflavanone, 7-hydroxyflavanone and rutin inhibited primary response. Levamisole slighly stimulated the primary and suppressed the secondary response. All the flavonoids tested decreased the manifestation of SRBC induced delayed type hypersensitivity reaction and showed no effect on classical or alternative pathway dependent hemolysis. The studies revealed the significant immunomodulatory potential of these flavonoids, methoxy derivatives having immunostimulatory activity and hydroxy derivatives immunosuppressive properties.

Immunostimulatory activity of Picrorhiza kurroa leaf extract.

A 50% ethanolic extract of Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) leaves (PKLE) was found to stimulate the cell-mediated and humoral components of the immune system as well as phagocytosis in experimental animals. PKLE elicited a dose-related increase in SRBC, induced 4 h (early) and 24 h (delayed) hypersensitivity reactions in mice and rats, and horse serum induced Arthus reaction in guinea pigs. It also enhanced the humoral immune responses in mice and rats and phagocytic function of the cells of the reticuloendothelial system in mice. PKLE exhibited no mitogenic activity but augmented the responsiveness of murine splenocytes to T cell mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) and B cell mitogen lipopolysaccharide (LPS E. coli).

Central nervous system effects of intrathecal muscle relaxants in rats.

When given for a sufficient time and dose intravenously, neuromuscular blocking drugs eventually can enter the cerebrospinal fluid (CSF). To study the potential pharmacologic consequences of neuromuscular blocking drugs in the CSF, a model was developed in the rat by using an intrathecal infusion of these drugs. A cannula was stereotaxically implanted in a lateral cerebral ventricle of anesthetized male Sprague-Dawley rats (250-300 g). Several days later, the effects of an intraventricular infusion (5 microL/min) of atracurium (0.804 mumol/mL), pancuronium (0.172 mumol/mL), and vecuronium (21.978 mumol/mL) were studied in unanesthetized rats. These rats (n = 6 in each group) exhibited dose-dependent hyperexcitability, during drug infusion, with seizures occurring at threshold doses of (mean), 0.12, 0.26, and 0.065 +/- 0.010 and 3.32 mumol/kg of atracurium, pancuronium, and vecuronium, respectively. The neuromuscular ED50 (intravenous dose required to produce a 50% depression of twitch tension) in rats determined by other investigators are 0.408, 0.115, and 0.352 mumol/kg for atracurium, pancuronium, and vecuronium, respectively. Therefore, seizure threshold doses were not related to the potencies of these drugs as neuromuscular blocking drugs. Based on these data, central nervous system effects were studied over the subseizure dose range approximating 1/100, 1/10, and 1/5 of the cumulative dose causing seizures for each drug (n = 5 for each dose). At 1/100 of seizure dose, decreased locomotor activity and piloerection occurred. At 1/10 to 1/5 of seizure dose, agitation, shivering, splayed limbs, and whole body shaking resulted.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypotensive activity of 8,24-euphadien-3 beta-ol (euphol).

8,24-Euphadien-3 beta-ol (euphol) on i.v. administration was found to exhibit a hypotensive activity in normotensive anesthetised dogs and rats which varied from a slight to a marked degree depending upon the dose range. Euphol inhibited various autonomic pressor and depressor responses. The hypotensive effect was not affected in dogs pretreated with atropine, antistine, and beta-blockers and in bilaterally vagotomised and carotid sinus denervated animals. The fall in blood pressure was enhanced in spinal transected and eviscerated dogs and after ganglion blockade with hexamethonium. Localisation of euphol to central cardiovascular loci displayed no effect on blood pressure. The LD50 in mice was found to be 1500 mg/kg i.p. and greater than 2 g/kg by the oral route.

Effect of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leucocyte migration.

Effect of alcoholic extract of salai guggal (AESG) was studied on cellular and humoral immune responses in mice and leucocyte migration in rats. Oral administration of AESG strongly inhibited the antibody production and cellular responses to sheep red blood cells in mice. It inhibited the infiltration of polymorphonuclear leucocytes and reduced the volume of pleural exudate in carrageenan induced pleurisy in rats. It showed no cytotoxic effect.

Immunomodulating agents of plant origin. I: Preliminary screening.

The immunobiological activity was investigated of certain medicinal plants widely used in the Ayurvedic and Unani systems of medicine for treatment of chronic infections and immunological disorders. The effect of an ethanolic extract of each drug was studied on delayed type hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant, stimulating both cell-mediated and humoral immunity. Tylophora indica, Aconitum heterophyllum and Holarrhena antidysenterica appeared to stimulate phagocytic function while inhibiting the humoral component of the immune system. Tinospora cordifolia and Ocimum gratissimum appeared to improve the phagocytic function without affecting the humoral or cell-mediated immune system. Hemidesmus indicus suppressed both the cell-mediated and humoral components of the immune system.