Anti-inflammatory activity of substituted 1,3,4-oxadiazoles

Various 2-(4-biphenoxymethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized by cyclization of the corresponding 1-(4-biphenoxyacetyl)-4-substituted thiosemicarbazides. These compounds were characterized by their elemental analyses and infrared, mass, and nuclear magnetic resonance spectral data. All substituted thiosemicarbazides (100 mg/kg, ip) and cyclized substituted oxadiazoles (100 mg/kg, ip) possessed anti-inflammatory activity, as reflected by their ability to provide protection against carrageenin-induced edema in the rat paw which ranged from 28 to 68% and 36 to 76%, respectively. Cyclization of the substituted thiosemicarbazides, in general, resulted in an increase in the anti-inflammatory activity of their corresponding substituted oxadiazoles, with the exception of those containing 2,4-dimethyl and 3,4-dimethyl substituents in their molecular structure. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip) were used as the standard reference drugs and these provided 45 and 53% protection, respectively. All compounds (1 mM) possessed antiproteolytic activity and the in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin ranged from 13 to 75% for substituted thiosemicarbazides and 39 to 70% for substituted oxadiazoles. There was no relationship between the anti-inflammatory activity of substituted thiosemicarbazides and substituted oxadiazoles and their antiproteolytic effectiveness. The low toxicity of these compounds was reflected by their high approximate LD50 values, ranging from 500 to 1000 mg/kg.     

Phaeochromocytoma presenting with cardiogenic shock and acute renal failure

A patient with a 12 hour history of headache, breathlessness and hypotension developed acute renal failure necessitating haemodialysis for 12 days. During recovery she developed hypertension, tachycardia and facial flushing. Investigations revealed a right adrenal phaeochromocytoma. Whilst postural hypotension is common in phaeochromocytoma, profound shock with acute renal failure is rare. This may have been precipitated by concomitant drug therapy, myocardial necrosis or by necrosis within the tumour.     

Tumour dormancy: initiation, maintenance and termination in animals and humans

The authors review the natural occurrence of tumour dormancy in man and animal models, which show the importance of cellular defence mechanisms in inducing and maintaining the state of tumour dormancy. Six cases of non-small-cell lung cancer are described. The patients exhibited moderate to very strong delayed hypersensitivity reactions to soluble lung-cancer antigen after specific immunotherapy. Three patients had nonregional metastases at 11, 12 and 14 years. Two had regional recurrence after 9 years, and in one patient a small hilar-node metastasis was found at autopsy after 7.6 years. In each case an immunodepressive event or drug treatment preceded resurgent growth. The effect of renal transplantation in patients with a history of surgery for cancer supports the conclusion that cellular defence mechanisms are crucial for the maintenance of tumour dormancy in man.     

Nasofacial conidiobolomycosis.

A case of Nasofacial Zygomycosis in a 15-year-old male patient from South India is reported. This patient had typical thickening of the nasofacial mucosa and the skin overlying it. The diagnosis was confirmed with fungal cultures. Although initially good response to treatment with potassium iodide was achieved, later the response was unsatisfactory, probably partly due to irregularity in treatment. Treatment with sulphamethoxazole--trimethoprim and prednisolone combination has resulted in remarkable improvement.     

Iron nutritional status of preschool children

Low hemoglobin and low MCHC levels were indicative of high incidence of iron deficiency in preschool children. The extent of iron deficiency as assessed by serum ferritin and free erythrocyte protoporphyrin showed a different trend. While FEP levels were highly suggestive of extensive iron deficiency (in 40–45% of children below the age of 5 years), low serum ferritin was seen in only 16–20% of children. The discrepant finding of high serum ferritin, and high erythrocyte protoporphyrin despite low MCHC in the present study, possibly reflects iron deficiency status along with chronic infection resulting in hyperferritinemia and hyperprotoporphyrinemia. It may be also due to associated folate deficiency resulting in non utilization of iron leading to the elevated levels of protoporphyrin.     

Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506. Mean survival time was increased significantly in these animals (p < 0.007) to 40.6 ± 25.6 days as compared with either untreated rats (10.0 ± 2.7 days) or rats treated with 0.04 mg/kg FK-506 alone (13.7 ± 4.2 days). Histologic examination demonstrated a significant reduction in the cellular infiltrate in rats treated with PEG-SOD plus FK-506, as compared with recipients treated with either agent alone or left untreated. Our results therefore suggest a potential approach to reducing immunosuppression in transplantation. (J ALLERGY CLIN IMMUNOL 1995;95:1276-81.)     

Mammalian sex chromosomes III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis inMus musculus

Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also.     

Studies on carboxymethylcellulose: Conductivity measurements of solutions, 2

The conductivity behaviour of carboxymethylcellulose (CMC) solutions was studied using different types of neutralizing reagents (LiOH, NaOH, KOH); the following order of conductance of CMC solutions was observed: Li⁺ < Na⁺ < K⁺. This conductance behaviour of CMC solutions with respect to the size of counterions is explained qualitatively as well as quantitatively. Binding of Li⁺, Na⁺ and K⁺ ions onto the polymer molecule and the influence of the degree of substitution, ,DS , on the conductivity of CMC were also investigated. The conductivity of CMC solutions as well as the fraction of bound counterions increase with increasing DS , at a given degree of neutralization (α) for each type of counterion. The effect of DS on the polymer charge fraction, i/s, is in line with the counterion condensation phenomena of Oosawa. The results regarding the dependence of the equivalent conductance of the polyion, Δ_p, on DS are compared with literature data.