Mucormycosis in Post Novel Corona Virus Patients: An Institutional Experience

Mucormycosis is an emerging angioinvasive fungal infection caused by ubiquitous saprophytic filamentous fungus that belongs to the class Zygomycosis. Mucormycosis or black fungus infections in patients with recent COVID-19 infections has given rise to a new epidemic during the second wave of this current COVID-19 pandemic in India. Steroid misuse, poor glycemic control, use of industrial grade oxygen, improper humidification and specific variants strains have resulted in profound immunosuppression and are attributed for the high incidence of COVID associated Mucormycosis (CAM) in India. The aims of the present study were to assess the age and gender specific incidence of CAM, the utility of special stains (PAS and GMS) for diagnosing mucormycosis (false negatives and sensitivity). In the present study emphasis was laid on identifying if there exists a correlation between host response, angioinvasion and bone invasion with mortality. The Present study is a retrospective, cross sectional analytical study taken up in the Department of Pathology, Guntur Medical College for a period of 2 months between 1st of May 2021 to 30th of June 2021. Results were tabulated in Microsoft excel 2016 and SPSS software version 14 was used for calculation of odds ratio and for performing multivariate analysis. All samples were routinely fixed using 10% buffered formalin, processed and sectioned. All the sections were stained with Haematoxylin and Eosin and also special stains for fungus like periodic acid Schiff (PAS) and Gomori Methenamine silver (GMS) were used wherever required. CAM is a serious complication after recovery from COVID-19 infection due to its high morbidity and mortality (13.7% in this series). CAM epidemiology and presentation is mostly similar to non-COVID mucormycosis seen in pre-COVID era.     

P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction

The p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production. RNAi-mediated down-regulation of endogenous p66shc led to activation of the proto-oncogene ras, and Akt kinase, with a corresponding increase in phosphorylation of eNOS at S1177 (S1179 on bovine eNOS). In rat aortic rings, down-regulation of p66shc suppressed the vasoconstrictor response to phenyephrine that was abrogated by treatment with the NOS inhibitor l-NAME, and enhanced vasodilation induced by sub-maximal doses of acetylcholine. These findings highlight a pivotal role for p66shc in inhibiting endothelial NO production, and endothelium-dependent vasorelaxation, that may provide important mechanistic information about endothelial dysfunction seen with aging.     

Natural products against cancer: Review on phytochemicals from marine sources in preventing cancer

Marine natural products have as of now been acknowledged as the most important source of bioactive substances and drug leads. Marine flora and fauna, such as algae, bacteria, sponges, fungi, seaweeds, corals, diatoms, ascidian etc. are important resources from oceans, accounting for more than 90% of the total oceanic biomass. They are taxonomically different with huge productive and are pharmacologically active novel chemical signatures and bid a tremendous opportunity for discovery of new anti-cancer molecules. The water bodies a rich source of potent molecules which improve existence suitability and serve as chemical shield against microbes and little or huge creatures. These molecules have exhibited a range of biological properties antioxidant, antibacterial, antitumour etc. In spite of huge resources enriched with exciting chemicals, the marine floras and faunas are largely unexplored for their anticancer properties. In recent past, numerous marine anticancer compounds have been isolated, characterized, identified and are under trials for human use. In this write up we have tried to compile about marine-derived compounds anticancer biological activities of diverse flora and fauna and their underlying mechanisms and the generous raise in these compounds examined for malignant growth treatment in the course of the most recent quite a long while.     

Induction of long-term immunity against respiratory syncytial virus glycoprotein by an osmotic polymeric nanocarrier

Respiratory syncytial virus (RSV) is one of the most common causes of viral deaths in infants worldwide, yet no effective vaccines are available. Here, we report an osmotically active polysaccharide-based polysorbitol transporter (PST) prepared from sorbitol diacrylate and low-molecular-weight polyethylenimine (PEI) showing a potent, yet safe, adjuvant activity and acting as an effective delivery tool for RSV glycoprotein (RGp) antigen. PST showed no toxicity in vitro or in vivo, unlike PEI and the well-known experimental mucosal adjuvant cholera toxin (CT). PST formed nano-sized complexes with RGp by simple mixing, without affecting antigenic stability. The complexes exhibited negative surface charges that made them highly efficient in the selective activation of phagocytic cells and enhancement of phagocytic uptake. This resulted in an improved cytokine production and in the significant augmentation of RGp-specific antibody production, which persisted for over 200 days. Interestingly, PST/RGp enhanced phagocytic uptake owing to the osmotic property of PST and its negative zeta potential, suggesting that PST could selectively stimulate phagocytic cells, thereby facilitating a long-lived antigen-specific immune response, which was presumably further enhanced by the polysaccharide properties of PST.     

Laser-induced effects in different biological samples

Experiments were carried out on cancerous HeLa cells and blood serum using a double integrating sphere and a He-Ne laser to investigate the optical properties and cellular effects due to photodynamic therapy (PDT). In the first experiment, HeLa cells were exposed to Photofrin at concentrations of 0, 10, 20, 30, 50 and 112.4 μg/ml at an irradiance of 0.2 W/cm² using diode laser light. Using a confocal microscope, cell debris and morphological changes in HeLa cells were recorded at different Photofrin concentrations. The results showed cell debris in HeLa cells at the highest concentration of Photofrin. In a second experiment, photobleaching was observed in HeLa cells in the presence of various concentrations of 5-aminolaevulinic acid ranging from 0–50 μg/ml. There was progressive degradation of the 635 nm peak during continuous laser irradiation at an irradiance of 0.2 W/cm². We conclude that cells demonstrating high initial fluorescence undergo bleaching at a faster rate than those with lower fluorescence. Finally in a third experiment, cancerous and noncancerous blood serum was irradiated at an irradiance of 0.1 W/cm² using a He-Ne laser in conjunction with a double integrating sphere system. Forward and back scattering of normal and malignant serum showed an exponential decrease in fluorescence amplitude. The results indicate that there is notable amplitude difference between malignant and normal blood serum with malignant blood serum showing decreased scattering. These results have important implications for photodiagnosis and photodynamic therapy.     

Multiparameter analysis of a screen for progesterone receptor ligands: comparing fluorescence lifetime and fluorescence polarization measurements

Direct measurement of the fluorescence lifetime (FLT) of a fluorescent label is an emerging method for high-throughput screening. Changes in the fluorescence lifetime can be correlated to changes in the non-radiative relaxation pathway(s) for the excited state of the label. These pathways can be environmentally sensitive, such as when a labeled analyte is free in solution versus bound to a receptor. Because lifetime is an intrinsic property of a fluorophore, it is not concentration dependent, and therefore has advantages similar to those of ratiometric fluorescent techniques such as fluorescence resonance energy transfer or fluorescence polarization. We have applied the FLT measurement technique to a screen of a small compound library in order to identify compounds that bind to the progesterone receptor, and compared the results to those obtained by performing the assay in fluorescence polarization mode. Each readout modality showed excellent Z'; values, with the FLT readout performing slightly better in this respect. Interfering compounds could be rapidly identified for either assay format by comparing the results between the two formats.     

Amelioration of cisplatin-induced toxicity in mice by carotenoid meso-zeaxanthin

Carotenoid meso-zeaxanthin ((3R, 3'S)-β, β-carotene-3,3'-diol [MZ]) was evaluated for its protective effect against cisplatin-induced nephrotoxicity in Swiss albino mice. Oral administration of MZ was started 5 days prior to cisplatin (16?mg/kg body weight, intraperitoneally as a single dose) injection. Animals in all groups were killed 72?h after cisplatin treatment. In serum, renal function markers like urea and creatinine, which were drastically elevated in cisplatin-treated control animals, were found to be decreased significantly by MZ pretreatment. Cisplatin-induced myelosuppression was also found to be significantly ameliorated by MZ as evident from the increase in white blood cell count, bone marrow cellularity and number of maturing monocytes in MZ-treated animals when compared with cisplatin alone-treated control animals. The levels of antioxidant enzymes-superoxide dismutase, catalase and glutathione peroxidase-as well as the glutathione level in the kidney were decreased after cisplatin treatment. But the levels were markedly increased by the carotenoid treatment in a dose-dependent manner. Addition of MZ was found to inhibit singlet oxygen produced by toluidine blue in vitro. Moreover, administration of MZ to the animals inhibited increased lipid peroxidation, conjugated dienes and hydroperoxides that are formed in the kidney by cisplatin administration. The results of histopathological analysis supported the protective potential of MZ against cisplatin-induced toxicity.     

Ultrasound diagnosis of fatty liver in patients with chronic liver disease: a retrospective observational study

OBJECTIVES: Hepatic ultrasound (US) is readily available and physicians usually trust the results of an US report suggesting fatty liver, but there are conflicting reports on its accuracy, especially in patients with chronic liver disease (CLD). Therefore, we retrospectively examined liver biopsies in patients with CLD and compared the histologic results to the hepatic US findings. METHODS: Liver biopsies were graded for fat (grades 0 to 3), inflammation (grades 0 to 4), and fibrosis (stages 0 to 4) in 131 patients with CLD (89% had chronic hepatitis C). Hepatic US interpretations were grouped into 3 categories-"normal," "fatty liver," and "nonspecific." A secondary analysis was performed using 3 sonographic categories based on the echogenicity: normal, "increased echogenicity," and "heterogenous." The US results were then compared with the liver biopsy results. RESULTS: A normal US report was associated with many false negatives, as 25% of these patients had fat (grades 1 to 3) on biopsy; furthermore, 46% had "significant fibrosis" (stages 2 to 4) or "significant inflammation" (grades 2 to 4). A "fatty liver" interpretation correctly identified fat on biopsy in 36.4% and "significant fat" (grades 2 to 3) in 11.4%, but 66% had significant fibrosis or significant inflammation. An US with increased echogenicity correctly identified fat in 43.5% and significant fat in 19.4%, but 69.4% had significant fibrosis or significant inflammation. The sensitivity of an US ranged from 11.4% to 88.2% and the specificity ranged from 40.4% to 86.2%, depending on the degree of steatosis on biopsy and the sonographic interpretation being considered. CONCLUSIONS: US is inaccurate for diagnosing hepatic steatosis in patients with CLD. Echogenic abnormalities are more likely to be the result of fibrosis or inflammation in this setting.