Design and Synthesis of New Methyl 1,2-Diaryl-4-Hydroxy-5-oxo -2,5-Dihydro-1H-Pyrrole-3-Carboxylate Derivatives as Selective COX-2 Inhibitors

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation and pain is often accompanied by adverse gastrointestinal and renal side effects. Their anti-inflammatory activity results from inflammation of cyclooxygenase (COX), which catalyzes bioconversion of arachidonic acid to prostaglandins. Nowadays, it is well established that there are at least two COX isozymes, COX-1 and COX-2. COX-1 is responsible for the physiological production of prostaglandins while COX-2 is responsible for the elevated production of prostaglandins during inflammation. Thus, selective inhibition of COX-2 over COX-1 is useful for the treatment of inflammation and inflammation associated disorders with reduced gastrointestinal toxicities compared to NSAIDs. The withdrawal of some diaryl heterocyclic selective COX-2 inhibitors due to the adverse cardiovascular side effects delineates the need to explore and evaluate a new structural ring template possessing COX inhibitory activity. Therefore, in this study, new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives were designed and synthesized based on the structure-activity relationship of selective COX-2 inhibitors. Target compounds were synthesized in two steps. In the first step, 4-(methylthio)benzaldehyde, arylamine derivatives, and dimethylacetylenedicarboxylate (DMAD) in the presence of para-toluene sulfonic acid (PTSA) were stirred in ethanol for 72 hours. After the completion of the reaction, the resulting product was filtered off and recrystallized with ethanol. In the second step, a solution of Oxone and water was added to a well-stirred solution of the resulting product and diethylamine in acetonitrile. After the completion of the reaction, the resulting precipitates were filtered off and recrystallized with ethanol. In this study, new derivatives of new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate were designed, synthesized, and purified. The structure of the synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. We designed and synthesized some new methyl 1,2-diaryl-4-hydroxy-5-oxo -2,5-dihydro-1H-pyrrole-3-carboxylate derivatives as selective COX-2 inhibitors. The structure of synthesized compounds was confirmed by FT- IR, 1HNMR, and MASS. The COX-2 inhibitory activity of these compounds is under investigation

Plasma Ammonia Levels in Newborns with Asphyxia

How to Cite This Article: Khalessi N, Khosravi N, Mirjafari M, Afsharkhas L. Plasma Ammonia Levels in Newborns with Asphyxia. Iran J Child Neurol. Winter 2016; 10(1):42-46.AbstractObjectivePerinatal asphyxia may result in hypoxic damage in various body organs, especially in the central nervous system. It could induce cascade of biochemical events leading to the cell death and metabolic changes, eventually may increase plasma ammonia levels. The purpose of this study was to determine the prevalence of hyperammonemia in neonates with asphyxia and to find the relationship between ammonia levels and severity of asphyxia.Material & MethodsIn this cross-sectional study, we included 100 neonates with perinatal asphyxia in the Neonatal Intensive Care Unit of Ali-Asghar Hospital, Iran University of Medical Science, Tehran, Iran in 2010-2011. All full term patients diagnosed of asphyxia were enrolled. The relationship between plasma ammonia levels and sex, gestational age, birth weight and severity of asphyxia were determined.Data were analyzed using SPSS software.ResultsFifty six percent of neonates were male. The mean gestational age was 38.0± 1.2 wk. Mean plasma ammonia level was 222 ± 100 μg/dl and 20% of the neonates had hyperammonemia. It was not associated with gender, gestational age, birth weight, and asphyxia severity. Six patients died and mean plasma ammonia levels was 206±122 μg/dl. In this group, there was no significant relation between plasma ammonia levels and severity of asphyxia. No significant different was seen between plasma ammonia in dead and lived neonates.ConclusionAccording to high prevalence of hyperammonemia in neonatal asphyxia, measurement of plasma ammonia levels, is suggested to improve management of asphyxia

The Prevalence of Acute Kidney Injury in Neonates with Asphyxia

Introduction: Asphyxia is a common cause of mortality and morbidity among neonates. Following severe asphyxia and ischemia, reperfusion occurs which damages vital organs like the kidneys. This study was conducted to determine the prevalence of AKI based on the definition of a serum creatinine level higher than 1.5 mg/dL, in neonates with asphyxia.Materials and Methods: This retrospective study was performed in Ali-Asghar and Shahid-Akbar-Abadi Hospitals, Tehran, Iran in a period of one year. The medical documents of all newborns diagnosed with asphyxia were studied. The asphyxia grade was determined according to the asphyxia Sarnat criteria. The kidney function was evaluated based on the serum creatinine level.Results: Thirty-eight cases met the inclusion criteria. There were 13 Sarnat grade-1 cases (34.2%), 19 grade 2 cases (50%), and 6 grade 3 patients (17.6%).  Three (7.8%) patients (2 patients in grade 3 and one patient in grade 2 of the Sarnat grading scale) developed AKI. AKI was detected in 33% of the patients in grade 3 and 5.2% of the patients in grade 2 of the Sarnat grading scale. Nine patients (23%) died, of whom 83% were in grade 3 and 16.9% in grade 2 of asphyxia.Conclusions: AKI developed in 7.8% of the cases, of whom 33% were in grade 3 and 5.2% were in grade 2 of the Sarnat grading scale. The low rate of AKI development in our study might be duo to the small sample size and patient mortality in the first 3 days of life.Keywords: Acute kidney injury; Neonates; Asphyxia

The Effects of Pre-feeding Oral Stimulations and Non-nutritive Sucking on Physical Growth and Independent Oral Feeding of Preterm Infants

Background: Breastfeeding failures and oral feeding problems in preterm infants result in long-term health complications. In this study, therefore, we aimed to evaluate the effect of oral stimulation along with non-nutritive sucking (NNS) on independent oral feeding initiation and weight gain in preterm infants. Methods: This prospective randomized clinical trial was carried out at Aliasghar Hospital in Tehran, Iran, 2014. A total of 50 26-32 weeks gestational age hospitalized infants, who were fed through tubes, were recruited in the study. The newborns were randomized into A, B and C groups. In the A and B groups, the neonates were stimulated through oral stimulation as well as non-nutritive sucking for 5 or 10 days, while in the group C, no especial intervention was performed. Infants' mean daily weight gain, the number of days until initiation of oral feeding, oral feeding progression, the number of days until reaching full oral feeding and date of discharge were recorded. The obtained data were analyzed and compared in the three groups using SPSS version 16.0. Results: Of all the participants, 25 cases (55.55%) were male. Mean gestational age at birth and mean birth weight were 28.64±1.93 weeks and 1337.11±185.07 grams, respectively. In the group A, newborns' weight at reaching four and eight oral feedings per day and their weights at discharge were significantly higher than the other two groups (P=0.016, 0.001 and 0.001, respectively). Mean daily weight gain in the group A was higher (84.2850 g) than the other groups (69.5814 vs. 64.2677 g). However, ANOVA results showed that this difference was not significant (P=0.108). Moreover, independent samples t-test indicated that this difference between groups A and C was significant (P=0.049). Conclusion: In clinically stable preterm neonates, oral stimulation and should be implemented to increase their weight; however, further studies are required to address this issue

Prevalence of Meningitis among Hospitalized Neonates with Urinary Tract Infection

Background: Bacteremia is relatively common in children with urinary tract infection (UTI). The aim of the present study was to determine the frequency of bacterial meningitis among neonates with laboratory-confirmed UTI.Methods: This retrospective cross-sectional study was performed on 163 hospitalized neonates in Ali Asghar and Shahid Akbarabadi hospitals affiliated to Iran University of Medical Sciences in Tehran, Iran. The demographic and clinical data of hospitalized neonates due to UTI during the recent 6 years (2010-2016) who were aged Results: A total of 163 neonates with laboratory-confirmed UTI with the mean age of 18.25±5.41 days were included. In this study, 54% of the neonates were male. Out of all neonates, 23 (14.1%) cases had positive blood culture. The positive CSF culture was observed in only two (1.2%) neonates. Positive voiding cystourethrogram (VCUG) test was reported in 50% of the neonates with positive CSF culture (P=0.047). Although abnormal ultrasound findings related to the urinary tract in positive CSF neonates were higher by approximately twofold, compared to those reported for negative CSF neonates, this difference was not statistically significant (50% and 24.2%, respectively; P=0.432).Conclusion: The frequency of the concurrent occurrence of UTI and meningitis in our neonates was 1.2%. Out of all indicators associated with meningitis occurrence, positive VCUG may be a risk factor. Further prospective studies are needed to approve these results