Synthesis of some new 2-(substituted-phenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazoles: a safer anti-inflammatory and analgesic agents

A series of 2-(substituted-phenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazoles (3-15) were synthesized. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation actions. The percentage inhibition in edema at different time intervals indicated that compounds 8, 11, 12, 14 and 15 exhibited good anti-inflammatory potential. The results illustrate that 2-(2-acetoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (15) and 2-(3,4-dimethoxyphenyl)-5-(N,N-diphenylaminomethyl)-1,3,4-oxadiazole (12) showed best anti-inflammatory activity among the series tested. Furthermore, activity is higher in case of chloro substitution as compared to methyl substitution. The compounds synthesized were also evaluated for their ulcerogenic and lipid peroxidation action and showed superior GI safety profile along with reduction in lipid peroxidation as compared to that of ibuprofen.     

Synthesis and biological evaluation of some novel 1,4-dihydropyridines as potential antitubercular agents

Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant antitubercular activity. In this study, we have synthesized new derivatives of 1,4-dihydropyridines bearing carbmethoxy and carbethoxy group at C-3 and C-5 of the 1,4-dihydropyridine ring. In addition, 1H-pyrazole ring is substituted at C-4 position. These analogues were synthesized by multi-component Hantzsch reaction. The in vitro antitubercular activity of compounds against Mycobacterium tuberculosis H(37) Rv was evaluated. The lowest minimum inhibitory concentration value, 0.02 μg/mL and SI > 500, was found for dimethyl 1,4-dihydro-4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 3f, diethyl 1,4-dihydro-4-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 4c and diethyl 1,4-dihydro-4-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethyl pyridine-3,5-dicarboxylate 4e, making them more potent than first-line antitubercular drug isoniazid. In addition, these compounds exhibited relatively low cytotoxicity.     

Role of hormones in acne vulgaris

Objective

To elucidate the role of endogenous hormones like testosterone, progesterone, estrogen, insulin-like growth factor, insulin and glucocorticoids in a common skin condition acne vulgaris.

Design and methods

We conducted a systematic review of the literature and abstracted the data for every published cut point.

Results

We screened more than 1000 studies and found that serum testosterone, progesterone, glucocorticoids, insulin and insulin-like growth factors are increased in patients with acne vulgaris and serum estrogen levels are low in patients.

Conclusions

Various endogenous hormones play important role in the pathogenesis of acne vulgaris. Thus, in the clinical practice it is important to evaluate serum levels of these hormones and patients must be treated accordingly to avoid serious endocrine disorders at an early age.     

Correlation of Intra Vascular Cannula Insertion Technique and Ward Practices with Local Site Infection

Background

Peripheral intravascular cannulas are indispensable in modern day medical care. These cannulas, if not inserted properly, predispose a patient to various morbidities. The present study was carried out to assess the incidence of intravascular cannula associated infections and correlate it with cannula insertion techniques and ward practices.

Methods

The study was carried out in the wards of a tertiary care hospital. The study was divided into two phases, each phase comprising of 50 patients. In phase 1, cannula insertion was carried out after normal ward cleaning practices. In phase 2, cleaning of the site was done by standard surgical cleaning procedure. The cannula samples after removal were cultured and local signs of thrombophlebitis looked for at the site of insertion. Thrombophlebitis was considered a surrogate marker of local infection in the vessel wall.

Result

The relative risk of acquiring thrombophlebitis increased by 2.18 times (applying univariate analysis) by existing methods as compared to the standard method.

Conclusion

Use of standard cleaning protocol had a significant effect on decreasing the incidence of cannula associated infections and cannula related morbidity.Key Words: Intravascular cannula, Peripheral vein thrombophlebitis, Cannula associated infections     

Toxicity of Low-Dose Intermittent Isotretinoin in Recalcitrant Acne

Background

Isotretinoin, an oral retinoid, has been utilized to achieve long term remissions in cases of recalcitrant acne. In the conventional dosage schedule, the use of oral isotretinoin has been limited by the occurrence of biochemical abnormalities such as hypertriglyceridaemia and impaired liver function tests and radiological changes consistent with diffuse idiopathic skeletal hyperostosis. Low-dose intermittent regimen of oral isotretinoin has been evolved as a cost effective alternative to the conventional dosage regimen in cases of acne. This study addresses the issue of adverse effects of low-dose intermittent isotretinoin and the safety of this regimen.

Methods

A total of 60 cases of recalcitrant acne were included in the study. Baseline haematological, biochemical and radiological investigations were carried out. Low-dose intermittent isotretinoin was instituted in a dose of 0.5 mg/kg/day for one week in every four weeks for six months. The investigations were repeated at the end of six months therapy.

Result

High triglyceride levels occurred in 5% of cases whereas impaired liver function tests and skeletal hyperostosis of the spine were not observed in any case after low-dose intermittent isotretinoin.

Conclusion

The low-dose intermittent regimen in cases of acne may be utilized to limit the systemic toxicity of oral isotretinoin.Key Words: Recalcitrant acne, Isotretinoin, Low-dose intermittent regimen     

Role of Estrogen in Regulation of Morphology and Synaptic Connectivity in Female Rat Subiculum

Estrogen is reported to exert neuroprotective influences on the cornu ammonis as well as the dentate gyrus, two of the three components of the hippocampal memory system. Subiculum, the third and the output component of this system, plays a vital role in retrieval of previously learnt information (recall tasks). We undertook these studies to understand estrogen's role in regulating the synaptic connectivity, neurotransmission and neural degeneration in subiculum. For this, we used brains of aged (16–18 months) post-estropausal female Wistar rats, and compared them with those of adult (4–5 months) ovary-intact, ovariectomized, ova riectomized-vehicle treated and ova riectomized-estrogen treated rats. The vehicle (sesame oil) and estrogen therapy. (17β estradiol, E2) were administered as daily subcutaneous injections (0.1 mg/kg of E2 in 0.1 ml vehicle) for 30 days. Serum estradiol assay was done to determine the levels of circulating serum estradiol levels. Brains were processed for Cresyl Violet, Golgi staining and Immunohistochemical studies [using anti-synaptophysin antibody].Our results indicate that estrogen deficiency (induced by normal ageing or by ovariectomy) results in subicular neuronal degenerative changes, decreased synaptic connectivity and reduced dendritic arborization, most of which are reasonably reversed with estrogen replenishment. These studies suggest a unique role of estrogen in preventing and even reversing the senile neurodegenerative changes in female subiculum.     

Dengue hemorrhagic fever: a rare cause of pituitary tumor hemorrhage and reversible vision loss

Dengue hemorrhagic fever leading to hemorrhage in pituitary adenoma is not reported till date: We herein report the first case of bilateral visual loss secondary to pituitary adenoma hemorrhage associated with dengue hemorrhagic fever. Urgent transnasal trans sphenoidal decompression of the macroadenoma prevented permanent visual loss in this patient. Pituitary apoplexy should be considered as differential diagnosis of visual deterioration apart from retinal hemorrhage, maculopathy, and optic neuropathy in cases of dengue hemorrhagic fever. Early decompression of optic nerves helped in the restoration of vision.