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Candida sp. impelled opportunistic infection in immune-compromised patients ensuing from asymptomatic colonization to pathogenic forms. Moreover, slow spread of Candida species inducing refractory mucosal and invasive infections brings acute resistance to antifungal drugs. Hence, here we probed the effect of encapsulated preparation of cinnamaldehyde (CNMA) in multilamellar liposomes (ML) against Candida albicans. The efficacy of ML-CNMA against Candida biofilm was assessed by scanning electron microscopy, transmission electron microscopy, as well as light microscopy and its percent inhibition, was determined by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] and crystal violet assay. ML-CNMA showed more fungicidal activity than free CNMA as well as multilamellar liposomal amphotericin B (ML-Amp B), which was further confirmed by spot test assay and Log-logistic dose–response analysis. Antifungal activity was driven by reactive oxygen species and cellular damage by sustained release of CNMA. Effect on hyphal formation during 48 h in presence/absence of ML-CNMA was observed under a microscope and further substantiated by RT-PCR by amplifying HWP1, the gene responsible for hyphal wall protein formation. Apoptotic programmed cell death was analyzed by FACS analysis which was further confirmed by cytochrome C release assay. This study elucidates the mechanistic insight of the enhanced antifungal activity of ML preparation of CNMA against Candida infections.

At the Aga Khan Hospital (AKUH), 65 infants presented with hypocalcaemic seizures, subsequently found to have rickets. Forty-six infants less than 6 months were totally or predominantly breast fed. In a subgroup of 15 mothers and their infants, we found very low plasma levels of 25(OH) vitamin D of < 5 micrograms/l and 7.5 +/- 3.3 micrograms/l, respectively. Neither mothers nor infants received vitamin D supplementation. Maternal vitamin D deficiency and non-supplementation in the infants were the likely causes of rickets in our patients. Prophylactic vitamin D 400 i.u. administered to infants up to 2 years and 800 i.u. to women in pregnancy and during lactation is recommended to prevent vitamin D deficiency.

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Dexamethasone accelerates the late gestational rise in rat lung catalase activity; neonatal hyperoxia elevates rat lung catalase activity. We studied the regulation of catalase gene expression in these instances. Catalase mRNA/mg DNA increased to gestation day 22 and then fell to the concentration in adult lungs. The rate of transcription of catalase mRNA was higher on gestation day 22 than gestation day 19, whereas the half-life of catalase mRNA (approximately 7 h) was the same on both days. Dexamethasone given 48 and 24 h before expected birth (gestation 22 days) increased catalase mRNA concentration at days 20 and 22 without a change in catalase mRNA stability. Early postnatal hyperoxia (greater than 95% O2, 72 h) elevated catalase mRNA/mg DNA and doubled its half-life without changing its rate of transcription. We conclude the normal late gestational elevation of catalase activity and the increase of activity during prenatal dexamethasone treatment are regulated at the level of gene transcription. By contrast, the elevation of catalase activity during neonatal hyperoxia is mediated posttranscriptionally by increased catalase mRNA stability.

IntroductionAcute appendicitis is one of the more common causes of acute abdominal pain. It occurs when the lumen of the appendix is obstructed, leading to inflammation and finally perforation. The preoperative differentiation of perforated from nonperforated appendicitis is important and helpful to define prognosis and determine an adequate therapeutic approach, including consideration for nonsurgical treatment. This study recommends computed tomography (CT), a noninvasive method of investigation, be used frequently in clinically suspected cases of perforated appendicitis in the Pakistani population for better patient outcomes.ObjectiveTo determine the diagnostic accuracy of CT in differentiating perforated from nonperforated appendicitis by using histopathology as the gold standard.Material and methodsA total of 236 patients with a clinical suspicion of appendicitis were included in this study. CT was performed in Liaquat National Hospital and Medical College. At the time of scanning, intravenous contrast was administered. Histopathology was used as the diagnostic gold standard. CT findings were documented using a proforma. The patient was returned to the referring department and followed after surgery for histopathology.ResultsSensitivity, specificity, and positive and negative predictive values, as well as the accuracy of CT in the detection of perforated appendicitis, was 71.4%, 90.7%, 62.5%, 93.6%, and 87.3%, respectively.ConclusionCT findings can be used to select patients with perforated appendicitis for initial nonoperative management.

We report a new protocol for inducing marked tolerance to prolonged exposure to hyperoxia in adult rats that entails the use of a single "rest period" between exposures to a usually lethal concentration of O2. Exposure of adult rats to greater than 95% O2 for 48 h followed by a rest in air, or a rest even in 50-75% O2, consistently resulted in 100% survival with evidence of only slight pulmonary edema during continuation of exposure to greater than 95% O2 for 3-7 more days (7-day survival for rats rested in room air for 24 h = 23/23; for rats rested in 50-75% O2 for 24 h = 27/27; for continuously O2-exposed control rats = 0/11). Induction of tolerance to hyperoxia was associated with significant increases in the lungs' antioxidant enzyme activities during the reexposure to greater than 95% O2 following the rest period. The molecular means by which the events in this protocol lead to increased lung antioxidant enzyme activity is only partially known, but because of the marked tolerance produced, the elucidation of the mechanisms must be important to our understanding of tolerance to hyperoxia.

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