Short-term Outcome and Predictors of Survival Among Neonates With Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative

Background: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. Objective: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. Setting: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. Study design: Retrospective cohort. Participants: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. Outcome: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. Results: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. Conclusion: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds

Comparative effect of Ocimum sanctum, Commiphora mukul, folic acid and ramipril on lipid peroxidation in experimentally-induced hyperlipidemia.

Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions.

Modulation of Oxidative Stress, Serum Lipids and Renal Dysfunction by Benazepril in Diabetes Mellitus.

Present study assessed the effect of benazepril on oxidative stress, serum lipids and renal dysfunction in alloxan induced diabetic rabbits. Benazepril reversed the increase in level of malondialdehyde and decrease in level of glutathione and superoxide dismutase activity caused by induction of diabetes. It also had a beneficial effect on diabetic dyslipidemia as manifested by elevation in serum HDL cholesterol. However, it had no effect on serum LDL, total cholesterol or triglycerides. Benazepril also attenuated the renal dysfunction induced by diabetes. It resulted in significant reduction in blood urea, serum creatinine and urine albumin excretion as compared to diabetic control rabbits. Further, kidney weight was significantly less in benazepril treated rabbits as compared to diabetic rabbits. To conclude, benazepril was found to be effective in preventing the oxidative stress and renal dysfunction as well as beneficial on serum lipids in experimentally-induced diabetes mellitus.

Peripheral interaction of opioid and nmda receptors in inflammatory pain in rats.

Both opioid and NMDA receptors have been known to be involved in pain processing in the central nervous system as well as in the periphery. The effect of drugs acting on opioid and NMDA receptors, and their role in modulation of pain response was observed in the formalin model of inflammatory pain in rats. We have demonstrated that morphine has significant antinociceptive effect in the formalin model and this effect was enhanced when given in combination with ketamine. We have also reported modulation of pain response when naloxone or NMDA were co-administered with morphine or ketamine in various combinations. A noteworthy observation in our study is that low dose naloxone when co-administered with ketamine and morphine, or with ketamine and NMDA, caused decrease in the pain response. These observations may suggest that low dose naloxone can cause modulation of opioid and NMDA receptors resulting in antinociceptive effect. Our study thus introduces a new concept of more than two drugs acting on opioid and NMDA receptors to modulate pain response.

Heavy metal induced oxidative stress & its possible reversal by chelation therapy.

Exposure to heavy metals is a common phenomenon due to their environmental pervasiveness. Metal intoxication particularly neurotoxicity, genotoxicity, or carcinogenicity is widely known. This review summarizes our current understanding about the mechanism by which metalloids or heavy metals (particularly arsenic, lead, cadmium and mercury) induce their toxic effects. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. The toxic manifestations of these metals are caused primarily due to imbalance between pro-oxidant and antioxidant homeostasis which is termed as oxidative stress. Besides these metals have high affinity for thiol groups containing enzymes and proteins, which are responsible for normal cellular defense mechanism. Long term exposure to these metals could lead to apoptosis. Signaling components affected by metals include growth factor receptors, G-proteins, MAP kinases and transcription factors. Chelation therapy with chelating agents like calcium disodium ethylenediamine tetra acetic acid (CaNa(2)EDTA), British Anti Lewisite (BAL), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), meso 2,3-dimercaptosuccinic acid (DMSA) etc., is considered to be the best known treatment against metal poisoning. Despite many years of research we are still far away from effective treatment against toxicity caused due to exposure to heavy metals/metalloids. The treatment with these chelating agents is compromised with number of serious side-effects. Studies show that supplementation of antioxidants along-with a chelating agent prove to be a better treatment regimen than monotherapy with chelating agents. This review attempts a comprehensive account of recent developments in the research on heavy metal poisoning particularly the role of oxidative stress/free radicals in the toxic manifestation, an update about the recent strategies for the treatment with chelating agents and a possible beneficial role of antioxidants supplementation to achieve the optimum effects. We have selected only arsenic, lead, mercury and cadmium for this article keeping in view current concerns and literature available.

Comparative hepatic and renal toxicity of cadmium in male and female rats.

Rats (male and female) were exposed to 0.5 mg/kg and 1 mg/kg cadmium as cadmium chloride for 3 days and subsequently sacrificed for cadmium concentration and other biochemical variables indicative of hepatic and renal damage. The absorption of cadmium was supported by biochemical changes, which were significantly higher in females than in males. This could be due to higher rate of intestinal absorption of cadmium in females than males. Male and female rats both showed relatively higher cadmium concentration in kidneys than in liver. Female rats also showed the similar trend in tissue metal levels as compared to male rats. However, hepatic and renal histopathological observations showed that female rats suffered from severe hepatic injury like hydropic degeneration of hepatocytes, granulation, bile duct proliferation etc. In comparison to female rats, male rats did not show much remarkable changes. Renal damage was more prominent in female than male in the form of renal tubular damage; most of the tubular nuclei were pyknotic, congestion of the boundary of cortex and medulla etc. The results suggested that females were comparatively more vulnerable to the toxic effects of cadmium than males.

Down syndrome with transient myeloid leukemia and urological abnormality.

Among the various anomalies associated with Down syndrome, leukemia is quite common. The variant transient myeloid leukemia is seen almost exclusively in the Down syndrome patients. On the other hand, urological anomalies are infrequently found both in the Down syndrome and leukemia patients. We report a case who had the rare combination of a urological anomaly along with Down syndrome and transient myeloid leukemia.