A comparison of different dosing regimen of intravenous paracetamol for hemodynamically significant patent ductus arteriosus closure in premature neonates <32 weeks: a prospective observational study.

OBJECTIVE: To compare the efficacy of low vs conventional dose intravenous paracetamol in early closure of haemodynamically significant patent ductus arteriosus within 7 days of life. METHODS: Preterm infants (<32 weeks of gestation) having echocardiographic evidence of hsPDA were given low dose (15 mg/kg initially followed by 7.5 mg/kg every 6 hourly) vs conventional dose (15 mg/kg every 6 hourly) for 5-7 days. RESULTS: In total, 56 infants (28 in each group) were enrolled. Ductal closure was achieved in 96% infants in the low-dose group and 100% infants in the conventional group (P = 1.00). Secondary outcomes, including ductal reopening and need for the second course of medical treatment (21% vs 3.5%, P = 0.1), median duration of hospital stay [30 (15, 43.5) vs 27 (18.5,45), P = 0.64], cumulative oxygen requirement [17.5 (7, 25) vs 14 (8.5, 25), P = 0.89], mortality (10.7% vs 25%, P = 0.29) and other morbidities, were comparable in both the groups. Median paracetamol levels were comparable in both the groups [53.4 µg/L (47, 2,70) vs 62.5 (55.6, 81.2), P = 0.67]. CONCLUSION: Low-dose paracetamol was non-inferior to conventional dose paracetamol for early ductal closure in preterm infants.

Comparison of WHO-UMC and Naranjo Scales for Causality Assessment of Reported Adverse Drug Reactions.

OBJECTIVES: The 2 most commonly used scales worldwide are the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and the Naranjo scales. The present study was planned to assess the degree of agreement between the 2 scales when the same adverse drug reactions (ADR) were assessed by 5 raters independently. METHODS: One hundred individual case safety reports were selected randomly from the ADR database of our institute and the details were emailed to 5 different experts (raters), who were DM Clinical Pharmacology residents from different institutes in India. An independent causality assessment of these ADRs was performed independently by these raters using both the WHO-UMC and Naranjo causality assessment scales. The agreement between the 2 scales was assessed for each rater using Cohen κ, and the overall interrater agreement was assessed using Fleiss κ. RESULTS: The Cohen κ level of agreement between the 2 scales for the 5 raters were substantial, fair, substantial, moderate, and substantial, respectively. The most common causality assessment category as per WHO-UMC scale was "possible" but varied among the raters on the Naranjo scale. No ADR was categorized as "certain" by any rater on the Naranjo scale. The Fleiss κ value for agreement among the 5 raters was found to be 0.2 (slight) for the WHO-UMC scale and 0.297 (fair) for the Naranjo scale. CONCLUSIONS: A moderate level of agreement was observed in this study between the WHO-UMC and Naranjo scales. The level of agreement among these 5 raters was found to be similar for the WHO-UMC and the Naranjo scales, indicating a similar degree of subjectivity for the 2 scales. Hence, more robust and less subjective scales are required for causality assessment.

Isolation and characterization of a novel hydrocarbonoclastic and biosurfactant producing bacterial strain: Fictibacillus phosphorivorans RP3.

In this study, an indigenous novel hydrocarbonoclastic (kerosene and diesel degrading) and biosurfactant producing strain Fictibacillus phosphorivorans RP3 was identified. The characteristics of bacterial strain were ascertained through its unique morphological and biochemical attributes, 16S rRNA sequencing, and phylogenetic analysis. The degradation of hydrocarbons by F. phosphorivorans RP3 was observed at Day 7, Day 10 and Day 14 of the experimental duration. GC-FID chromatograms demonstrated a significant increase in hydrocarbon degradation (%) with progressing days (from 7 to 14). The bacterium exhibited capability to utilize and degrade n-hexadecane (used for primary screening) and petroleum hydrocarbons (kerosene and diesel; by ≥ 90%). With increase in the number of experimentation days, the optical density of the culture medium increased, whereas pH declined (became acidic) for both Kerosene and Diesel. Absence of resistance to routinely used antibiotics makes it an ideal candidate for future field application. The study is, thus, significant in view of toxicological implications of hydrocarbons and their degradation using environmentally safe techniques so as to maintain ecological and human health.

Persistent Muscle Twitching With Phenobarbitone in a Preterm Neonate-Lack of Response or Manifestation of Toxicity?

BACKGROUND: Phenobarbitone is frequently used for the treatment of seizures in neonates, but it has a narrow therapeutic index. CASE PRESENTATION: A 28-week preterm infant born of vaginal delivery developed signs and symptoms suggestive of ventriculitis on day 9. After an episode of clonic seizures on day 11, phenobarbitone was administered intravenously at a loading dose of 20 mg/kg followed by maintenance doses of 6 mg/kg per day in 2 divided doses for 5 days. Due to suspected recurrence of seizures, a mini-loading dose of 10 mg/kg was administered on day 16; after which the child became unresponsive, hypotonic, and comatose with generalized slowing on electroencephalography. Pupils were dilated and fixed, and deep tendon reflexes were absent. Spontaneous respiration was depressed which resulted in ventilatory support. While awaiting the therapeutic drug monitoring results, 2 additional doses of 5 mg/kg of phenobarbitone were administered due to the persistence of muscle twitching. The phenobarbitone level (164 mcg/mL) was alarmingly above the normal range, warranting immediate discontinuation of the drug. This led to reduction in the plasma phenobarbitone levels into the therapeutic range (37 mcg/mL) over the next 10 days with subsequent improvement in the neurological status and respiration. CONCLUSIONS: Phenobarbitone levels are reported to be greater in preterm infants as compared to term infants. Persistence of seizures and muscle twitching on phenobarbitone could either be due to a lack of response or a manifestation of drug toxicity. This case underlies the importance of therapeutic drug monitoring, which can distinguish between the 2 causes, thus enabling the clinician to make an appropriate decision.

Hypersensitivity with Inhalational Budesonide: An Under Recognised Entity.

Hypersensitivity reactions are commonly encountered with drugs such as beta lactams, sulphonamides, allopurinol etc., Corticosteroids are frequently employed in the treatment of drug induced allergic reactions. Therefore, it is highly unlikely that a corticosteroid itself may cause such a reaction as an adverse effect. We had encountered a rare case of hypersensitivity reaction with inhalational budesonide in an eight-year-old boy. The patient developed maculopapular rashes over the back, buttocks and legs accompanied with pruritus within four hours of administration of the first dose. The reaction subsided within two days on withdrawal of the drug and treatment with oral fexofenadine. Re-introduction of budesonide by the same route after a month resulted in appearance of similar reaction. Both the parents of the patient were known cases of allergic rhinitis suggesting allergic pre-disposition in the family. Causality analysis using WHO-UMC scale suggested certain association of this allergic reaction with inhaled budesonide.

Pharmacological Properties and Therapeutic Potential of Naringenin: A Citrus Flavonoid of Pharmaceutical Promise.

Naringenin chemically known as 5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one is a common dietary polyphenolic constituent of the citrus fruits. It has received considerable attention for pharmaceutical and nutritional development due to potent pharmacological activities and therapeutic potential. Accruing evidence from both in vitro and in vivo studies have unraveled numerous biological targets along with complex underlying mechanisms suggesting possible therapeutic applications of naringenin in various neurological, cardiovascular, gastrointestinal, rheumatological, metabolic and malignant disorders. Functionally, this ameliorative effect of naringenin is primarily attributed to its antiinflammatory (via inhibiting recruitment of cytokines and inflammatory transcription factors) and anti-oxidant (via scavenging of free radicals, bolstering of endogenous antioxidant defense system and metal ion chelation) effects. The present article provides a comprehensive review of the various studies that have evaluated the therapeutic potential of naringenin and its actions at the molecular level. It also summarizes the pharmacokinetic data and issues and challenges involved in pharmaceutical development and suggest that it may be a potential agent for further exploration as well as may be useful as a dietary adjunct in treatment of various human ailments.

Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats.

The clinical use of doxorubicin is associated with dose limiting cardiotoxicity. This is a manifestation of free radical production triggered by doxorubicin. Therefore, we evaluated the efficacy of febuxostat, a xanthine oxidase inhibitor and antioxidant, in blocking cardiotoxicity associated with doxorubicin in rats. Male albino Wistar rats were divided into four groups: control (normal saline 2.5mL/kg/dayi.p. on alternate days, a total of 6 doses); Doxorubicin (2.5mg/kg/dayi.p. on alternate days, a total of 6 doses), Doxorubicin+Febuxostat (10mg/kg/day oral) and Doxorubicin+Carvedilol (30mg/kg/day oral) for 14days. Febuxostat significantly ameliorated the doxorubicin-induced deranged cardiac functions as there was significant improvement in arterial pressures, left ventricular end diastolic pressure and inotropic and lusitropic states of the myocardium. These changes were well substantiated with biochemical findings, wherein febuxostat prevented the depletion of non-protein sulfhydryls level, with increased manganese superoxide dismutase level and reduced cardiac injury markers (creatine kinase-MB and B-type natriuretic peptide levels) and thiobarbituric acid reactive substances level. Febuxostat also exhibited significant anti-inflammatory (decreased expression of NF-κBp65, IKK-ß and TNF-α) and anti-apoptotic effect (increased Bcl-2 expression and decreased Bax and caspase-3 expression and TUNEL positivity). Hematoxylin and Eosin, Masson Trichome, Picro Sirius Red and ultrastructural studies further corroborated with hemodynamic and biochemical findings showing that febuxostat mitigated doxorubicin-induced increases in inflammatory cells, edema, collagen deposition, interstitial fibrosis, perivascular fibrosis and mitochondrial damage and better preservation of myocardial architecture. In addition, all these changes were comparable to those produced by carvedilol. Thus, our results suggest that the antioxidant and anti-apoptotic effect of febuxostat contributes to its protective effects against doxorubicin-induced cardiotoxicity.

Preclinical evidence for the pharmacological actions of naringin: a review.

Naringin, chemically 4',5,7- trihydroxyflavanone-7-rhamnoglucoside, is a major flavanone glycoside obtained from tomatoes, grapefruits, and many other citrus fruits. It has been experimentally documented to possess numerous biological properties such as antioxidant, anti-inflammatory, and antiapoptotic activities. In vitro and in vivo studies have further established the usefulness of naringin in various preclinical models of atherosclerosis, cardiovascular disorders, diabetes mellitus, neurodegenerative disorders, osteoporosis, and rheumatological disorders. Apart from this, naringin has also exerted chemopreventive and anticancer attributes in various models of oral, breast, colon, liver, lung, and ovarian cancer. This wide spectrum of biological expediency has been documented to be a result of either the upregulation of various cell survival proteins or the inhibition of inflammatory processes, or a combination of both. Due to the scarcity of human studies on naringin, this review focuses on the various established activities of naringin in in vitro and in vivo preclinical models, and its potential therapeutic applications using the available knowledge in the literature. Additionally, it also encompasses the pharmacokinetic properties of naringin and its inhibition of CYP isoenzymes, and the subsequent drug interactions. Moreover, further clinical research is evidently needed to provide significant insights into the mechanisms underlying the effects of naringin in humans.

Syzygium cumini ameliorates insulin resistance and ß-cell dysfunction via modulation of PPAR, dyslipidemia, oxidative stress, and TNF-α in type 2 diabetic rats.

Syzygium cumini (SC) is well known for its anti-diabetic potential, but the mechanism underlying its amelioration of type 2 diabetes is still elusive. Therefore, for the first time, we investigated whether SC aqueous seed extract (100, 200, or 400 mg/kg) exerts any beneficial effects on insulin resistance (IR), serum lipid profile, antioxidant status, and/or pancreatic ß-cell damage in high-fat diet / streptozotocin-induced (HFD-STZ) diabetic rats. Wistar albino rats were fed with HFD (55% of calories as fat) during the experiment to induce IR and on the 10th day were injected with STZ (40 mg/kg, i.p.) to develop type 2 diabetes. Subsequently, after confirmation of hyperglycemia on the 14th day (fasting glucose level > 13.89 mM), diabetic rats were treated with SC for the next 21 days. Diabetic rats showed increased serum glucose, insulin, IR, TNF-α, dyslipidemia, and pancreatic thiobarbituric acid-reactive substances with a concomitant decrease in ß-cell function and pancreatic superoxide dismutase, catalase, and glutathione peroxidase antioxidant enzyme activities. Microscopic examination of their pancreas revealed pathological changes in islets and ß-cells. These alterations reverted to near-normal levels after treatment with SC at 400 mg/kg. Moreover, hepatic tissue demonstrated increased PPARγ and PPARα protein expressions. Thus, our study demonstrated the beneficial effect of SC seed extract on IR and ß-cell dysfunction in HFD-STZ-induced type 2 diabetic rats.

Safety of single-dose nevirapine for prevention of vertical transmission of human immunodeficiency virus infection.

INTRODUCTION: Nevirapine administered as a single dose each to the mother and child within 72 h after birth is used to prevent vertical transmission of human immunodeficiency virus (HIV) under the prevention of parent to child transmission of HIV program (PPTCT). The efficacy of nevirapine in this regard has been proved beyond doubt, but there are unresolved questions about its safety. Hence, the primary objective of this study was to evaluate the safety of this regime. MATERIALS AND METHODS: HIV-positive pregnant women who consented to participate in the study received a single oral dose of 200 mg nevirapine at the onset of labor followed by administration of 2 mg/kg of nevirapine syrup to the newborn within 72 h of birth. Both mother and child were followed up for 1 week postpartum to note the occurrence of any adverse reactions. RESULTS: The mother and child followed up for 1 week postpartum did not show any serious adverse reactions in the present study. Mothers reported adverse reactions like nausea, vomiting, and headache which were self-limiting and did not require any intervention. CONCLUSION: The present study substantiates the safety of nevirapine.

Severe irritant contact dermatitis induced by povidone iodine solution.

Albeit uncommon occurrence, irritant contact dermatitis induced by povidone iodine can be an unfortunate adverse reaction complicating its use as an antiseptic. We hereby present the case report of a patient who suffered such a reaction as a result of exposure to povidone iodine, employed as an antiseptic during spinal anesthesia. On conservative management with soframycin ointment, the lesions resembling chemical burns healed in a month without extensive scarring or other complications.