Amphotericin B in the management of COVID-19 associated mucormycosis

Background: Amphotericin B is considered the drug of choice for primary treatment of mucormycosis. During second wave of COVID-19 pandemic there was severe scarcity of liposomal amphotericin B. This study aims to determine role of various formulations of amphotericin and their side effects when used for the treatment of COVID-19 associated mucormycosis. Methods: A retrospective study was conducted between May 2021 and December 2021 at a tertiary care centre. 380 patients with post-COVID rhino-orbito-cerebral mucromycosis (ROCM) were included in the study. Liposomal amphotericin B, conventional amphotericin deoxycholate, lipid complex amphotericin B was used in the treatment. Patients were observed for side effects like fever, chills, rigors, hypokalemia, renal function derangements, thrombophlebitis and respiratory difficulties. Results: Majority of patients received liposomal amphotericin B (331) and 31 patients received conventional amphotericin deoxycholate and 5 patients were given lipid complex amphotericin B injections. The most commonly encountered side effects were of the mild type constituting chills (98% with liposomal and 100% with amphotericin deoxycholate), and fever (94% with liposomal and 74% with amphotericin deoxycholate). Conclusions: Our study highlights the role of various formulations of amphotericin B in the treatment of COVID-19 mucormycosis.

Estimated Deficits in Nutrient Intake of ICDS Beneficiaries Who Receive Take Home Ration at Two Districts in Karnataka

Background: The current estimates of energy and protein to bridge nutrient gap in the beneficiaries of the Integrated Child Development Services (ICDS) supplementary nutrition program use sub-optimal methodology for deficit calculation. Objective: To estimate the nutrient deficit and the risk of inadequate nutrient intake in beneficiaries of the ICDS, aged 6-36 months, using individual 24-hour diet recalls, from districts of Chitradurga and Davanagere in Karnataka. Study design: Cross-sectional design. Participants: Children (aged 6 to 36 months) registered as beneficiaries of the ICDS in these districts. Methods: Data were collected on socio-demographic factors, child feeding patterns, perception and usage of take home ration (THR), between August to October, 2019. Three non-consecutive days’ 24-hour diet recall data of children were obtained from mothers, and anthropometric measurements were taken. The proportion of children at risk of inadequate nutrient intakes was estimated using the probability approach. Assuming that 50% of a healthy population will be at risk of nutrient inadequacy such that intake and requirement distributions overlap, the proportion at actual risk of nutrient inadequacy (?50%) was calculated. Results: A combined district analysis showed a median energy deficit of 109 kcal and 161 kcal in children belonging to the age groups of 6-12 month and 13-36 month, respectively. The actual risk of inadequate intake for both age groups ranged between 12- 47% for fat and other micronutrient (iron, calcium, zinc, folate, vitamin B12 and vitamin A), despite breastfeeding, complementary feeding and reported THR use. Conclusion: Children who receive supplementary nutrition as part of the national program fail to meet their nutrient requirements that are essential for growth and development. The study results may help in strengthening the IYCF counselling and in modification of the existing THR, with quality and cost implications.

Chronic Anti-Inflammatory Activity of Ethanolic Extract of Leaves of Clerodendrum viscosum by Carrageenin Induced Paw Oedema in Wistar Albino Rats.

Aims: The aim of the study was to investigate chronic anti-inflammatory activity of ethanolic extract of the leaves of Clerodendrum viscosum (EELCV) by carrageenin induced paw oedema in Wistar albino rats. Study Design: Prospective. Place and Duration of Study: Dept of Pharmacology, Yenepoya Medical College, Yenepoya University, Derlakatte, Mangalore 575018, Karnataka, India. June 2010-August 2010. Methodology: Dried powdered leaves of Clerodendrum viscosum were subjected to Soxhlet extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines no. 423, three doses of the test drug was selected (75, 150 & 300 mg/kg) for rats, and were subjected to screening for anti-inflammatory activity. Results: Oral administration of EELCV at doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) has shown significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar albino rats compared to control. A significant inhibition of oedema formation was also observed at 4th hour. Conclusion: Administration of EELCV orally at the doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) showed significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar Albino rats. The percentage inhibition of the oedema at 3rd hour was 63.75 % for the dose of 150 mg/kg and 46.30 % for the dose of 300 mg/kg. A significant inhibition was also observed at 4th hour.

Acute anti-inflammatory activity of ethanolic extract of leaves of Leucas indica by carrageenan induced paw oedema in wistar albino rats.

Background: Inflammation is basically a defense phenomenon but can lead to serious pathological conditions. It is treated by various agents with good to moderate success because of both considerable toxicity and side effects. There are various mediators to cause an inflammatory reaction that can contribute to the associated symptoms and tissue injury. Even though non steroidal anti-inflammatory drugs are the most commonly prescribed drugs in the world, their use as anti-inflammatory agents continues to be principally limited by their undesired side effects. Hence, the traditional medical practitioners and scientists are turning towards Indian System of Medicine (ISM). Methods: Dried powdered leaves of Leucas indica were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines No. 423, three doses of the test drug 75, 150 & 300mg/kg were selected and subjected to preclinical anti-inflammatory screening by carrageenin induced paw oedema in Wistar Albino rats. Results : Oral administration of Ethanolic Extract Of Leaves of Leucas Indica (EELLI) at doses of 150 mg/kg and 300mg/kg showed significant anti-inflammatory activity 52.58% (p<0.01) and 36.87% (p<0.05) respectively compared to control. Conclusion: Even though oral administration of EELLI has shown significant anti-inflammatory activity, further studies are required to evaluate its comprehensive analysis including quantitative / semi quantitative analysis, characterize its chemical structure and assess its pharmacotherapeutic activities with exact mechanism of action as an anti-inflammatory agent.

Chronic central and peripheral analgesic activity of ethanolic extract of the leaves of clerodendrum viscosum in rodent models.

The aim of the study was to investigate the chronic peripheral analgesic activity of Ethanolic Extract of the leaves of Clerodendrum viscosum (EECV) by acetic acid induced writhing reflex test in mice and chronic central analgesic activity of EECV by tail immersion method in rats. Dried powdered leaves of Clerodendrum viscosum were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines No. 423, three doses of the test drug was selected and were subjected to chronic analgesic activity. EECV showed significant chronic peripheral analgesic activity (p<0.01) in mice in the dose of 200 mg / kg and moderate analgesic activity at the dose of 400 mg/kg (p<0.05) as compared to control and the standard drug Indomethacin. But failed to show any chronic central analgesic activity by tail immersion method at any of the three doses selected compared to control and standard drug Pentazocin in rats.

Recent advances in diagnosis of filarial infections.

Improved diagnostic methods for human filariasis are needed to facilitate surveillance activities, to monitor control efforts and to evaluate new drugs and vaccines. Currently, diagnosis of filarial infections largely depends upon detection of worms themselves, principally of microfilariae in blood or skin. In many infected people with lymphatic filariae, microfilariae (MF) are not detectable in blood, and removal of skin snips for detection of microfilariae in onchocerciasis seems a rather primitive technique. In addition, because the clinical manifestations of filariae vary greatly between individuals, an ideal diagnostic test would not only reveal individuals that are infected or have been exposed to infection, but would also differentiate between various clinical manifestations that the lymphatic-dwelling parasites, in particular, induce in the infected population. This is important because the pathological reactions induced following treatment with diethylcarbamazine vary with the clinical picture induced by the lymphatic filariae. They are certainly a major problem in onchocerciasis. Recent advances in biotechnology have started revolutionizing the diagnosis of filarial parasites not only in the host but also in their vectors. Monoclonal antibodies have been developed that are specific for detection of circulating antigens in lymphatic filariasis. Species-specific DNA probes have been developed for Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, and Loa loa. Diagnostic antigens have been obtained by cloning parasite DNA that codes for proteins recognized by infected individuals with only certain species of filariae. Recombinant antigens (rAgs) are available today which detect prepatent infections in onchocerciasis. Several laboratories developing new diagnostic tests for filariasis are currently evaluating these tests in the field with the collaboration of parasitologists, epidemiologists, and vector biologists.

Sharing of antigens among filarial species revealed by antibody dependent cell-mediated reactions.

Antisera raised in albino rats against microfilariae of Litomosoides carinii, Brugia pahangi, Brugia malayi and sera from Bancroftian elephantiasis patients promoted rat neutrophil-mediated adherence and cytotoxicity to the microfilariae. Pre-treatment of the immune sera, with microfilarial antigen at a final concentration of 5 and 25 μg per ml blocked cellular adherence and cytotoxicity to the microfilariae indicating the presence of crossreactive antibodies. The heterologous immune sera were effective in eliminating the circulating Litomosoides carinii microfilariae in Mastomys natalensis.

Brugia malayi: serum dependent cell-mediated reactions to microfilariae.

Sheathed and exsheathed microfilariae of Brugia malayi are killed by normal rat cells in the presence of immune serum in vitro. Immune serum heated at 56 degrees C for 1 hour lost this activity which was largely restored by the addition of fresh normal rat serum. EDTA but not EGTA abolished this activity indicating the operation of complement by alternate pathway. Fresh normal rat serum alone promoted cellular adherence without exerting cytotoxicity to the microfilariae. The activity in the immune serum could be removed with Staphylococcus aureus cells containing Protein A or anti-IgG antiserum. The activity could also be absorbed to and eluted from Protein A--sepharose CL-4B suggesting the involvement of IgG. Neutrophils and macrophages participate in the antibody dependent cell-mediated cytotoxicity phenomenon. Eosinophils while adhering to the microfilariae exert cytotoxicity only to the exsheathed parasites.