Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients.

PURPOSE: To report a series of 13 immunocompetent patients who developed new-onset uncontrolled diabetes mellitus (DM) following COVID-19 infection and presented as rhino-orbital mucormycosis (ROM). METHOD: Retrospective study. RESULTS: A total of 127 patients of COVID-19 Associated Mucormycosis (CAM) were evaluated at four centres in India. All patients underwent endoscopic sinus debridement surgery and received systemic amphotericin-B therapy. Five patients (5/13; 38.4%) received retrobulbar amphotericin-B injections. Orbital exenteration was performed in advanced orbital involvement or progression of orbital disease in spite of maximal medical therapy. In his cohort, 13/127 (10.2%) patients presented with new onset DM, where one patient had bilateral disease. The mean age was 35.9 years (range: 20-51 years) and the mean duration from diagnosis of COVID-19 to the diagnosis of mucormycosis was 14.2 days. While 7/13 (53.8%) of the patients received systemic corticosteroids during the course of their treatment for COVID-19, six patients received no steroids or immunomodulators. The mean follow-up period was 9.2 weeks (range: 3-18 weeks) following discharge. Life salvage was possible in 100% of the cases. While overall globe salvage was possible in 42.8% (6/14 eyes), the globe could be preserved in 4/5 patients who received retrobulbar amphotericin-B injections. CONCLUSIONS: Those involved in the care of COVID-19 patients should be aware about the possibility of recent-onset DM, even in patients without a history of corticosteroid therapy. Rarely, recent-onset DM following COVID-19 may present as rhino-orbital mucormycosis, which requires aggressive surgical and medical intervention.

Clove bud oil reduces kynurenine and inhibits pqs A gene expression in P. aeruginosa.

Quorum sensing (QS), a communication system involved in virulence of pathogenic bacteria like Pseudomonas aeruginosa is a promising target to combat multiple drug resistance. In vitro studies using clove bud oil (CBO) in P. aeruginosa revealed a concentration dependent attenuation of a variety of virulence factors including motility, extracellular DNA, exopolysaccharides and pigment production. Furthermore, treatment with CBO demonstrated a distinct dose-dependent reduction in biofilm formation as well as promoting dispersion of already formed biofilm, observations that were also supported by porcine skin ex vivo studies. Expression studies of genes involved in signalling systems of P. aeruginosa indicated a specific decrease in transcription of pqsA, but not in the lasI or rhlI levels. Additionally, the expression of vfr and gacA genes, involved in regulation, was also not affected by CBO treatment. CBO also influenced the PQS signalling pathway by decreasing the levels of kynurenine, an effect which was reversed by the addition of exogenous kynurenine. Though the synthesis of the signalling molecules of the Las and Rhl pathways was not affected by CBO, their activity was significantly affected, as observed by decrease in levels of their various effectors. Molecular modelling studies demonstrated that eugenol, the major component of CBO, favourably binds to the QS receptor by hydrophobic interactions as well as by hydrogen bonding with Arg61 and Tyr41 which are key amino acid residues of the LasR receptor. These results thus elucidate the molecular mechanism underlying the action of CBO and provide the basis for the identification of an attractive QS inhibitor.

A novel, versatile cannula for vitreoretinal surgery: Bapaye aspiration scraper - Initial experience.

The induction of posterior vitreous detachment (PVD) is an important step in the successful outcome of vitreoretinal surgery for various indications. This may pose a significant challenge intraoperatively in cases of strong adhesion between the posterior hyaloid and retina. Various techniques to achieve intraoperative PVD have been described which involve active aspiration as well as non-aspiration techniques to achieve a plane of separation between the posterior hyaloid and retina. Very frequently, combinations of these techniques might be necessary to achieve successful PVD induction. We describe a novel instrument that combines aspiration as well as non-aspiration techniques for PVD induction, Bapaye aspiration scraper. It is also useful in various vitreoretinal interface procedures due to its design and is compatible with small-gauge vitrectomy systems which are commonly used in modern vitreoretinal surgery.

A Simple Bioanalytical Method for Simultaneous Estimation of Amlodipine and Celecoxib in Rat Plasma by High Performance Liquid Chromatography.

A simple, precise, rapid and accurate UFLC method has been developed with due validation for the simultaneous estimation of Amlodipine besylate and Celecoxib in rat plasma. The separation has been taken place by C18 Eclipse plus column at 1ml/min flow rate. The mobile phase comprises of 20 mM sodium acetate buffer of pH 4.5 adjusted with glacial acetic acid and methanol (30:70% v/v). The effluents were monitored at 228 nm with a total run time of 15min. The retention time of Amlodipine besylate and celecoxib were found to be 7.69 min and 10.69 min respectively. The extraction of drugs have been achieved by protein precipitation technique with methanol as a solvent. The detection concentration was linear over 60-420 ng/ml for Amlodipine besylate and 600-4200 ng/ml for Celecoxib. Regression equation of Amlodipine besylate and Celecoxib were found to be y = 30.996x + 520.29 & y = 39.722x + 23706 with regression coefficient 0.9944 & 0.9941 respectively using unweighted and weighted linear regression with a weighting factor of 1/x0, 1/x, 1/✓x and 1/x2. The percentage recoveries were found to be 88.52±1.276 to 93.06±2.872 for Amlodipine & 89.40±0.728 to 94.05±0.221 for Celecoxib. This liquid chromatography method was extensively validated for linearity, accuracy precision, and stability studies.

Simultaneous Bilateral Central Retinal Artery Occlusion following COVID-19 Infection.

Purpose: Coronavirus-19 disease (COVID-19) has been associated with a high risk of thrombotic complications. Here, we report the case of a patient who developed simultaneous bilateral retinal artery occlusion following COVID-19 infection.Case Report: A 42-year-old male with no systemic co-morbidities presented with sudden, painless loss of vision in both eyes. Fundoscopy showed retinal edema and cherry-red spots in both eyes. Fluorescein angiography showed reperfusion, absence of choroidal ischemia, and Optical Coherence Tomography showed thickened inner retinal layers suggestive of retinal edema and the outer retinal layers appeared intact. Blood investigations for vasculitis, coagulation profile, lipids, and homocysteine level were within normal limits.Conclusion: COVID-19 patients may develop a systemic coagulopathy and acquired thrombophilia characterized by a tendency for venous, arterial, and microvascular thrombosis. This hypercoagulable state is believed to be a hyperinflammatory response; physicians and ophthalmologists, alike, should be aware of these possible long-term sequelae.

Guidelines for the management of ocular trauma during the COVID-19 pandemic.

As the COVID-19 pandemic rages on, India is recording a very high number of new cases daily; even as the country prepares to gradually "unlock", after months of lockdown. While elective eye surgeries such as uncomplicated cataract surgeries, blepharoplasty and eyelid procedures and refractive surgeries can be planned at a later date; emergency cases pertaining to ocular trauma cannot be deferred. This manuscript gives a brief overview of the general guidelines for the management of ocular trauma during the COVID-19 pandemic.

Experimental therapeutic intervention with alpha tocopherol in ethanol induced testicular injuries in rats.

Infertility is well-established harmful effect in chronic alcoholism and so far, there is no effective treatment for this condition. The study was conducted to determine the effects of alpha tocopherol on ethanol induced testicular injuries in male albino rats of Wistar strain. Five groups (n=6) of animals were used. Group I served as control. Group II received daily 1.6g ethanol/kg body weight/day for 4 weeks orally. Group III received 1.6g ethanol+80mg alpha tocopherol/kg body weight/day for four weeks orally. Group IV received 1.6g ethanol/kg body weight for/day 4 weeks and followed by 80mg alpha tocopherol/kg body weight/day for four weeks orally. Group V received 1.6g ethanol/kg body weight/day orally for 4 weeks, followed by 4 weeks abstinence. Twently-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and used for the estimation of extent of lipid peroxidation and tissue levels of antioxidants and steroidogenic enzymes. Alpha tocopherol treatment increased the activities of testicularΔ(5), 3ß-HSD. Moreover, the treatment was also associated with significant decrease in testicular oxidative stress. Ethanol-induced oxidative stress and decreased steroidogenesis can be reversed by treatment with alpha tocopherol.

Alcohol abuse-duration dependent decrease in plasma testosterone and antioxidants in males.

Ethanol is a testicular toxin and it causes fertility abnormalities with low sperm count and impaired sperm motility in men. The present study was designed to investigate plasma testosterone level and hypothalamic pituitary gonadal (HPG) axis function in alcoholic men and also effect of ethanol on systemic oxidative stress. Forty six male alcohol abusers in the age group 20-40 years were selected. Fifty five, males in the same age group served as control. Alcohol abusers had significantly low plasma testosterone with low luteinizing hormone and follicle stimulating hormone. In addition they had significantly high thiobarbituric acid reactive substances (TBARS), superoxide dismutase and glutathione S-transferase, and low glutathione, ascorbic acid, catalase, glutathione reductase and glutathione peroxidase. Moreover, serum testosterone level in alcoholics negatively correlated with duration of alcohol abuse, and TBARS. Duration dependent decreased serum testosterone level in alcohol abusers might be due to 1) increased oxidative stress which can damage Leydig and supporting Sertoli cells and 2) impaired HPG axis.

Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction.

The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa and contaminating leukocytes has been defined as one of the few etiologies for male infertility. Administration of antioxidants in patients with 'male factor' infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. Mammalian spermatozoa membranes are very sensitive to free radical induced damage mediated by lipid peroxidation, as they are rich in polyunsaturated fatty acids. Limited endogenous mechanisms exist to reverse these damages. ROS attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. ROS induced DNA damage accelerate the germ cell apoptosis. Unfortunately spermatozoa are unable to repair the damage induced by excessive ROS as they lack the cytoplasmic enzymes required to accomplish the repair. Assessment of such oxidative stress status (OSS) may help in the medical treatment. Treatment strategies must be directed toward lowering of ROS levels to keep only a small amount necessary to maintain normal cell function.

Impaired hypothalamic-pituitary-gonadal axis function in men with diabetes mellitus.

In view of association of diabetes mellitus and male infertility, present study was designed to investigate the functional status of hypothalamic pituitary gonadal (HPG) axis in diabetic men. Thirty-five diabetic men (BMI 22.24±0.21) in the age group 20-40 (30.6±4.7) years were selected. Twenty-five healthy men (BMI 23.85±0.25), in the same age group (29.5±4.8) served as control. Blood samples were collected for hormonal and biochemical estimations. Diabetic men had significantly low serum testosterone with low LH and FSH, hypercholesterolemia, hypertriglyceridemia, hypoalbuminemia and increased oxidative stress. Low serum testosterone in diabetic men was accompanied by low LH and FSH; the inability of the pituitary gland to respond appropriately to a decline in testosterone implying central effect of high serum glucose on the interaction between the nervous and endocrine system. Nutritional deficiency, increased oxidative stress and increased aromatase activity due to excessive body fat might have also contributed to low serum testosterone.

Association of plasma level of thiobarbituric acid reactive substances with extent of hepatocellular injury in preterm infants with cholestatic jaundice.

The present study was designed to determine the association between extent of hepatocellular injury and plasma level of thiobarbituric acid reactive substances (TBARS) in pre term infants with cholestasis. Preterm infants (<35 weeks gestation) admitted to the neonatal intensive care unit were enrolled (with their parents informed consent) in either the 'cholestasis' group (if their direct bilirubin was >2 mg/dl) (n=25) or in the control group (n=16). Blood samples for measurement of TBARS, direct bilirubin and transaminases were obtained with-in 24 hours of enrollment. The cholestasis and control groups were comparable with respect to gestational age, birth weight and Apgar score. Serum direct bilirubin, SGOT (EC 2.6.1.1) and SGPT (EC 2.6.1.2) levels were significantly high in the cholestasis group. Plasma levels of TBARS in cholestasis group were correlated with SGOT (F=276.92; P<0.0001) and SGPT (F=355.17; P<0.0001) and differed significantly between cholestatic and control infants. Our findings suggest that oxidative stress in preterm infants with cholestasis is associated with hepatocellular injury.

Experimental therapeutic intervention with ascorbic acid in ethanol induced testicular injuries in rats.

Ascorbic acid treatment significantly increased the activities of testicular delta5, 3beta-HSD and 17beta-HSD. Moreover, the treatment was also associated with significant decrease in oxidative stress in the testis. Ethanol induced oxidative stress and decreased steroidogenesis can be reversed by treatment with ascorbic acid.

Effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity in rats.

In order to find out the effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzyme activity, male rats fed with ethanol 1.6g/kg body weight per day for four weeks were studied. Besides a drastic reduction in body and testis weight, there was decrease in ascorbic acid, reduced glutathione and activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in the testicular tissue of the treated animals. Simultaneously, there was increase in lipid peroxidation and glutathione S-transferase activity. Activities of 3 beta-hydroxy steroid dehydrogenase and 17 beta-hydroxy steroid dehydrogenase were also found decreased in the treated animals. The results indicate that chronic ethanol administration resulted in increase in oxidative stress and decrease in the activities of steroidogenic enzymes in the rat testes.

Effect of ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate on ethanol induced hypoproteinemia and hyperlipidemia in rats.

We studied effect of exogenous ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate on serum lipids and proteins in experimental hepatotoxic Wistar rats. Eleven groups (n = 6) of animals were used. Hepatotoxicity was induced by administering ethanol (1.6 g/kg/day) for 28 days. Both preventive and curative options were studied. Percentage increase in body weight was significantly lower in ethanol treated rats. Ethanol significantly (P<0.05) increased cholesterol, triglycerides and LDL, and decreased protein, albumin and A:G ratio in serum. Ascorbic acid, alpha-tocopherol, lecithin and L-ornithine-L-aspartate exhibited an ability to counteract the alcohol-induced changes in the body weight and biochemical parameters in preventive and therapeutic models in varying degree. Antioxidants showed better effect.

Effect of exogenous lecithin on ethanol-induced testicular injuries in Wistar rats.

Infertility is well-established harmful effect in chronic alcoholism and so far, there is no effective treatment for this condition. The study was conducted to determine the effects of lecithin, a known hepatoprotective on ethanol induced testicular injuries in male albino rats of Wistar strain. Five groups (n=6) of animals were used. Group I served as control. Group II received daily 1.6 g ethanol/kg body weight/day for 4 weeks orally. Group III received 1.6 g ethanol + 500 mg lecithin/kg body weight/day for four weeks orally. Group IV received 1.6 g ethanol/kg body weight for/day 4 weeks and followed by 500 mg lecithin/kg body weight/ day for four weeks orally. Group V received 1.6 g ethanol/kg body weight/ day orally for 4 weeks, followed by 4 weeks abstinence. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and used for the estimation of extent of lipid peroxidation and tissue levels of antioxidants and steroidogenic enzymes. Lecithin protected testes from ethanol induced oxidative stress. However, the drug did not show any considerable effect on the activities of testicular delta5, 3beta-HSD and 17beta-HSD. In conclusion, ethanol induced oxidative stress can be reversed by treatment with lecithin. However the effect of lecithin on steroidogenesis was not promising.

Role of oxidative stress in ethanol induced germ cell apoptosis - An experimental study in rats.

The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 µ thin paraffin sections of testis. Testicular homogenate was prepared and centrifuged. The supernatant was used for the estimation of extent of lipid peroxidation and antioxidant defense status. There was significant reduction in body weight: and in testicular weight and diameter in ethanol treated rats. Extent of germ cell apoptosis was significantly high in ethanol treated rats. Ethanol treated rats showed significantly high tissue TBARS level and glutathione S-transferase activity; and low tissue ascorbic acid, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Chronic ethanol administration resulted in high oxidative stress in the testes either due to increased extent of lipid peroxidation or due to decreased antioxidant defenses, and thereby induces germ cell apoptosis leading to testicular atrophy.

Evidence for oxidative stress in osteoarthritis.

Evidence of increased oxidative stress in patients of osteoarthritis in comparison with healthy control subjects was investigated by measuring the thiobarbituric acid reactive substances (TBARS), vitamin C, reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in erythrocytes. It was observed that osteoarthritis patients were more susceptible to oxidative damage than controls as evident from increased TBARS and decreased ascorbic acid, GSH, catalase and GPx in erythrocytes. Significant increase in SOD activity found in patients might be an adaptive response. With the understanding of the role of antioxidants in arthritis, it is becoming increasingly clear that these agents seem to be beneficial in osteoarthritis.

Factors delaying hospital arrival of patients with acute stroke.

BACKGROUND: Low rates of thrombolysis for ischemic stroke in India and other developing countries have been attributed to delays in presentation to the hospital. MATERIALS AND METHODS: A prospective study was carried out during a 12-month period ending December 2012 in the department of Neurology, Malabar Institute of Medical Sciences, Kerala, India, to look for the factors contributing to delay in hospital arrival of patients with acute stroke. Patients and or their relatives were interviewed within 48 hours of admission using a structured questionnaire. RESULTS: A total of 264 patients attending the emergency department were included. There were 170 men and 94 women. The mean age was 61.5 ± 12.4 years. A total of 67 (25%) patients presented within 4 hours of stroke onset. Factors associated with early arrival (multivariate logistic regression analysis) were distance 15 km or less from hospital (P 0.03, odds ratio (OR) 2.7), directly reaching the stroke department (P < 0.001, OR 9.7), history of coronary artery disease (P 0.001, OR 3.84), higher educational status (P 0.001, OR 3.7), and presence of hemiplegia (P 0.001, OR 5.5). CONCLUSIONS: We found a considerable delay in the early arrival of patients to our stroke department. Health promotion strategies to improve community awareness of early symptoms of stroke, education of local physicians about the importance of early referrals to the stroke centers, and wider availability and use of ambulance services are promising methods to help expedite presentation to hospital post stroke and thereby improve the management of stroke in India.