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Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing ‘fit-for-use’ diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Three-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings.
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Background: Cardiotoxicity is one of the most feared side effects of anticancer agents like Doxorubicin. Asparagus racemosus is a widely used medicinal plant in Indian system of medicine known for its antioxidant activity. In certain studies ethanol extract of Asparagus racemosus has shown to possess cardioprotective activity in experimental animals while in some other studies cardioprotective potential of Asparagus racemosus has not been demonstrated. Therefore, due to the controversial action, the present study was designed to explore the cardioprotective effect of aqueous effect of Asparagus racemosus against doxorubicin induced cardiotoxity.Methods: Following approval from Institutional Animal Ethics Committee of L.L.R.M Medical College registered under CPCSEA, India, this study was conducted in which 30 rats were randomized into five groups of six rats each. Group I received 2 ml/kg b.w. normal saline p.o for 21 days, group II apart from receiving pellet diet and normal saline for 21 days were treated with Doxorubicin in a single dose of 20 mg/kg intraperitoneally on the 21st day, group III and group IV received aqueous extract of Asparagus racemosus in doses of 250 mg/kg/day and 500 mg/kg/day respectively p.o. for 21 days followed by administration of Doxorubicin (20 mg/kg i.p.) on the 21st day, Group V received Carvedilol in doses of 30 mg/kg/day p.o. for 21 days followed by administration of Doxorubicin (20mg/kg i.p) on the 21st day. Then they were anaesthetized and blood sample was collected from abdominal aorta for performing blood test i.e. Creatinine kinase MB fraction (CK-MB), Lactate dehydrogenase (LDH), Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruvate transaminase (SGPT). After blood collection the animals were sacrificed and heart was dissected out for histopathological study. The data obtained was organized and analysed by suitable statistical methods i.e. ANOVA followed by Post Hoc test.Results: CK-MB, LDH, SGOT and SGPT levels were found to be significantly raised (p<0.001) in Doxorubicin treated group. Asparagus racemosus pretreated groups exhibited significant limitation (p<0.001) in rise in levels of CK-MB,LDH,SGOT and SGPT levels in a dose dependent manner following Doxorubicin administration which were comparable to the group treated with the standard cardioprotective drug Carvedilol. Histopathological changes further corroborated cardioprotective potential of Asparagus racemosus.Conclusions: The present study concluded that aqueous extract of Asparagus racemosus possess cardioprotective potential against Doxorubicin induced cardiotoxicity.
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Background: Gentamicin induced nephrotoxicity is a major contributor to Acute Kidney Injury (AKI) resulting from free radicals induced oxidative stress. Tinospora cordifolia is an Indian medicinal plant, widely used because of its antioxidant activity. Due to limited scientific literature exploring its nephroprotective potential, the present study was designed to investigate the nephroprotective effect of aqueous extract of Tinospora cordifolia against gentamicin induced nephrotoxicity in albino rats.Methods: The study was commenced following approval from Institutional Animal Ethical Committee of L.L.R.M. Medical College, Meerut (UP). Twenty four rats were randomised into four groups of six animals each. Total duration of study was 21 days. Group I received normal saline p.o., group II received normal saline along with gentamicin on last 5 days, group III and IV received Tinospora cordifolia in graded doses p.o. along with gentamicin on last 5 days. Injection gentamicin (40mg/kg) i.p. was given once daily for last 5 days to induce nephrotoxicity in rats of groups II, III and IV. The rats were sacrificed under anaesthesia, blood samples analysed for blood urea nitrogen (BUN) and serum creatinine levels and histopathological changes were studied. Statistical analysis was done using ANOVA followed by post hoc test.Results: Tinospora cordifolia pre-treated groups exhibited significant (p<0.001) limitation in rise in levels of BUN and serum creatinine in a dose dependent manner. Histolopathological observations further corroborated the biochemical findings.Conclusions: The present study concluded that aqueous extract of Tinospora cordifolia possesses nephroprotective potential against gentamicin induced nephrotoxicity.
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Background: Aegle marmelos (A. marmelos), a medicinal herb, is widely used in the Indian system of medicine for treatment of various ailments. The methanolic extract of A. marmelos leaves had shown antioxidant effect. However, so far aqueous extract of A. marmelos is not scientifically evaluated for its cardio protective potential. Hence the present study was designed to find out cardio protective role of A. marmelos against doxorubicin induced cardiotoxicity.Methods: Thirty rats were randomized into five major groups (n=6). Group I received only 2ml/100g/day normal saline p.o., group II received 2ml/100g/day of normal saline p.o. followed by doxorubicin on 21st day, group III received carvedilol 30 mg/kg/day p.o., Group IV received A. marmelos 250mg/kg/day p.o. and Group V received A. marmelos 500mg/kg/day p.o. for 21days. Doxorubicin 20mg/kg i.p. single dose was given to induce cardiotoxicity in rats of group II, III, IV and V respectively on last day of experiment. Animals were sacrificed 48 hours after doxorubicin administration. Cardiac serum markers creatinine phosphokinase MB, lactate dehydrogenase, serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase were analysed biochemically. Histopathological changes were studied under light microscope.Results: All cardiac serum marker levels were found significantly (p<0.001) increased in doxorubicin group while A. marmelos pre-treated group displayed significant (p<0.001) reduction in rise of these parameters in a dose dependent manner indicating cardio protection. Histological observations further correlated the cardio protective effect of A. marmelos.Conclusions: The present study concluded that aqueous extract of A. marmelos possesses cardio protective potential against doxorubicin induced cardiotoxicity.
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Food based approach is a more practical and sustainable approach to combat micronutrient deficiencies including vitamin A deficiency in India. However several gaps of knowledge with respect to the stability of β- carotene from foods and therefore its bioavailability exist. The present study aimed to assess the total and beta- carotene content of 4 vegetables (Coriandum sativum), Amaranth, Red (Amaranthus sp); Green garlic (Allium Sativum) and Mogri (Raphanus caudatus); and study the stability of beta carotene using minimal processing and addition of weak acids from foods, and product development using of coriander leaves. Results indicate that among the four vegetables, beta-carotene content of coriander was highest (2921.79 μg / 100 g) and lowest for mogri (425.15μg/100g). When coriander leaves were macerated alone in an electric mixer grinder and with green chilies, lemon or both, retention of beta carotene was 72.3%, 149.81%, 98.2%, and 182% resp. indicating the enhancing effects of green chillies and lemon juice of β- carotene retention. The fresh coriander leaves when incorporated into a recipe retained 75.47% of total carotene and 74.185 of β- carotene and was found to be highly acceptable using the composite score and hedonic test. The study indicates that minimal processing and usage of green chillies and lime in carotene rich foods enhance its retention. Efforts should be directed towards development of acceptable recipes incorporating green leafy vegetables and thereby resulting in an increased intake of β-carotene rich indigenous foods.
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Epigenetic modifications such as acetylation and deacetylation of histone proteins play a decisive role in transcriptional alteration and expression of genes. Acetylation is catalysed by the histone acetyl transferases enzymes and activates expression of genes by converting chromatin into a less compact, transcriptionally active state. Histone deacetylases enzymes catalyze deacetylation that condenses chromatin into a closed structure .Consequently transcriptional factors are unable to access DNA and gene expression is suppressed. Balanced activity of HATs and HDACS is essential for normal gene expression. Increased HDAC activity can lead to imbalance in protein acetylation resulting in hypoacetylation, tight chromatin structure and suppression of various genes. This aberrant suppression of genes is the hallmark of several malignant and other diseases including neurodegenerative disorders. Histone Deacetylase Inhibitors (HDACIs) have potential to restore the balance of histone acetylation that reverses the silencing of pathological genes. Thus HDACIs modify expression of genes without affecting sequence of DNA and act as epigenetic modifiers. Vorinostat and romidepsin are FDA approved HDACIs. Valproic acid, belinostat and many others are in different phases of clinical trials. This review article explores the target based epigenetic mechanisms as well as existing and potential therapeutic role of HDACIs in various malignant and non-malignant diseases. Data sources were articles published in medical journals and bibliographic database Medline.
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Apparent hemoglobinopathy acquired after blood transfusion is an uncommon cause of diagnostic dilemma resulting in repeated testing and delay in the diagnosis. Out of the 1530 hemoglobin (Hb)- high-performance liquid chromatography (HPLC) performed at our hospital (May 2009 to April 2010), 3 pediatric cases of thalassemia major were detected having posttransfusion hemoglobinopathy with HbS ranging from 9.9% to 18.5%. In all three cases, there was no variant hemoglobin in earlier documented Hb-HPLC. It is important to be aware of and consider apparent transfusion-induced hemoglobinopathy in patients with unusual percentage of variant hemoglobin to avoid unnecessary treatment and counseling.