Successful Management of a Child with Bronchoesophageal Fistula Associated with Other Anomalies.

Bronchoesophageal fistulas (BEFs) are rare malformations characterized by abnormal communication between the bronchus and the esophagus. Herein, we report a successful management of a child with BEF discovered as an intraoperative surprise and associated with the short gut, annular pancreas, and disorder of intestinal fixation.

Syntheses, Molecular Docking and Biological Evaluation of 2-(2- hydrazinyl)thiazoles as Potential Antioxidant, Anti-Inflammatory and Significant Anticancer Agents.

BACKGROUND: Recently, researchers have worked on the development of new methods for the synthesis of bioactive heterocycles using polyethylene glycol as a green solvent. In this context, we report the synthesized 2-(2-hydrazinyl) thiazoles for their in vitro antioxidant, in vitro anti-inflammatory and in vitro anti-cancer activities. OBJECTIVE: The objective of the study was to develop novel antioxidant, anti-inflammatory and anti-cancer drugs. METHODS: At the outset, the condensation of substituted acetophenones 1, thiosemicarbazide 2, and α-haloketones 3 was carried out using PEG-400 (20 mL) in the presence of 5 mol% glacial acetic acid to afford thiosemicarbazones intermediate. Furthermore, these thiosemicarbazones were reacted with α-haloketones 3 to obtain appropriate 2-(2-hydrazinyl) thiazoles. The synthesized compounds were in vitro tested for their antioxidant, anti-inflammatory, and anti-cancer activity. RESULTS: In vitro evaluation report showed that nearly all molecules possessed potential antioxidant activity against 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR) and hydrogen peroxide (H2O2) radical scavenging activity. Most 2-(2-hydrazinyl) thiazoles derivatives have shown potential anti-inflammatory activity as compared to diclofenac sodium as a reference standard. 2-(2-Hydrazinyl) thiazoles derivatives showed significant anticancer activity for human leukemia cell line K-562 compared to adriamycin as a reference standard. CONCLUSION: All tested compounds showed potential 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging activity. Among the tested series, 4b, 4d and 4e exhibited good hydrogen peroxide and 4b, 4e, 4f and 4g showed excellent superoxide radical scavenging activity. In addition, the 4b, 4e and 4g compounds revealed potent in vitro anti-inflammatory activity against standard diclofenac sodium drug. 2-(2-Hydrazinyl) thiazole derivatives, such as 4c and 4d, showed significant anticancer activity against human leukemia cell line K-562. Thus, these molecules provide an interesting template for the design and development of new antioxidant, anti-inflammatory, and anti-cancer agents.

A Novel Method for the Syntheses of Imidazo-Thiadiazoles as Potential Antioxidants and Anti-Inflammatory Agents.

BACKGROUND: A literature survey revealed that many imidazo-thiadiazole molecules were used as key intermediates for the development of novel drugs. The synthesized imidazo-thiadiazole derivatives were tested for their in vitro antioxidant and anti-inflammatory properties. The purpose of this research paper is to provide readers with information regarding diseases caused by free radicals. OBJECTIVE: The objective of this study is to develop novel antioxidant and anti-inflammatory drugs. METHODS: Imidazo-thiadiazole derivatives 5a-f were synthesized through cyclo-condensation reactions in two steps. First, the synthesis of 2-amino-thiadiazole derivatives from substituted aromatic carboxylic acids and thiosemicarbazide by using POCl3 as a solvent as well as a catalyst was performed. In the next step, imidazo-thiadiazoles were prepared from 2-amino-thiadiazole derivatives with appropriate α-haloketones in the presence of polyethylene glycol-300 (PEG-300) as a green solvent. These imidazo- thiadiazole derivatives were prepared by using a novel method. The synthesized compounds were in vitro tested for their antioxidant and anti-inflammatory activities. RESULTS: In vitro evaluation report showed that nearly all molecules possess potential antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR), and hydrogen peroxide (H2O2) radical scavenging activity. Most of the imidazo-thiadiazole derivatives have shown significant anti-inflammatory activity as compared to diclofenac sodium as a reference standard. CONCLUSION: In the search for novel therapies to treat inflammation and oxidation, we have made efforts to develop anti-inflammatory and antioxidant agents with a preeminent activity. Imidazo-thiadiazoles 5a, 5e as well as 5f showed potential anti-inflammatory activity. All tested imidazo-thiadiazole deriv-atives (5a-f) showed potential antioxidant activity against one more radical scavenging species as com-pared to ascorbic acid as the reference standard. Thus, imidazo-thiadiazole derivatives constitute an interesting template for the design and development of new antioxidant as well as anti-inflammatory agents.

Modeling the Effect of Amino Acids and Copper on Monoclonal Antibody Productivity and Glycosylation: A Modular Approach.

In manufacturing monoclonal antibodies (mAbs), it is crucial to be able to predict how process conditions and supplements affect productivity and quality attributes, especially glycosylation. Supplemental inputs, such as amino acids and trace metals in the media, are reported to affect cell metabolism and glycosylation; quantifying their effects is essential for effective process development. We aim to present and validate, through a commercially relevant cell culture process, a technique for modeling such effects efficiently. While existing models can predict mAb production or glycosylation dynamics under specific process configurations, adapting them to new processes remains challenging, because it involves modifying the model structure and often requires some mechanistic understanding. Here, a modular modeling technique for adapting an existing model for a fed-batch Chinese hamster ovary (CHO) cell culture process without structural modifications or mechanistic insight is presented. Instead, data is used, obtained from designed experimental perturbations in media supplementation, to train and validate a supplemental input effect model, which is used to "patch" the existing model. The combined model can be used for model-based process development to improve productivity and to meet product quality targets more efficiently. The methodology and analysis are generally applicable to other CHO cell lines and cell types.

Metal-free oxidative coupling of arylmethylamines with indoles: a simple, environmentally benign approach for the synthesis of 3,3'-bis(indolyl)methanes.

The efficient metal-free oxidative coupling of arylmethylamines with indoles has been developed using molecular oxygen as a green oxidant. The present reaction provides a novel route towards the synthesis of 3,3'-bis(indolyl)methanes in excellent yields of up to 95% via C-C and C-N bond formation. This attractive and environmentally friendly one-pot protocol is a simple procedure that features inexpensive acetic acid as the catalyst and molecular oxygen as the sole oxidant, and it supports a wide substrate scope with the good tolerance of functional groups.

Lessons Learnt in The Management of Acute Complications following Liver Injury in Children

Purpose@#Liver injuries constitute an important cause of hospital admissions, pediatric morbidity, and sometimes mortality. This study was undertaken to assess the spectrum of pediatric liver injuries with special emphasis on the management of acute complications. @*Methods@#This retrospective study used data from the Department of Pediatric Surgery, Bangalore Medical College, Bengaluru, India, between March 2013 and March 2019. All children between 1-18 years were included in the study (n = 33). Children were assessed with relevance to age, sex, mode of injury, hemodynamic stability at admission, need for blood transfusions, surgery, radiological investigations, complications, total number of days of stay in hospital, and mortality. @*Results@#There were 27 (81.8%) males and 6 (18.18%) were females. The most common cause for injury was a road traffic accident (60.6%). The majority (nearly 65%) of pediatric liver injuries were Grade II and III. There were 4 children who had post traumatic complications including 2 pseudoaneurysms, 1 inferior vena cava thrombus, and 1 bile leak with a biloma formation which were managed appropriately. @*Conclusion@#Timely and appropriate radiological evaluation is required for assessments of complications. The majority of complications can be managed conservatively, and minimally invasive techniques like endoscopic retrograde cholangiopancreatography is helpful in the management of complications.

Lessons Learnt in The Management of Acute Complications following Liver Injury in Children

Purpose@#Liver injuries constitute an important cause of hospital admissions, pediatric morbidity, and sometimes mortality. This study was undertaken to assess the spectrum of pediatric liver injuries with special emphasis on the management of acute complications. @*Methods@#This retrospective study used data from the Department of Pediatric Surgery, Bangalore Medical College, Bengaluru, India, between March 2013 and March 2019. All children between 1-18 years were included in the study (n = 33). Children were assessed with relevance to age, sex, mode of injury, hemodynamic stability at admission, need for blood transfusions, surgery, radiological investigations, complications, total number of days of stay in hospital, and mortality. @*Results@#There were 27 (81.8%) males and 6 (18.18%) were females. The most common cause for injury was a road traffic accident (60.6%). The majority (nearly 65%) of pediatric liver injuries were Grade II and III. There were 4 children who had post traumatic complications including 2 pseudoaneurysms, 1 inferior vena cava thrombus, and 1 bile leak with a biloma formation which were managed appropriately. @*Conclusion@#Timely and appropriate radiological evaluation is required for assessments of complications. The majority of complications can be managed conservatively, and minimally invasive techniques like endoscopic retrograde cholangiopancreatography is helpful in the management of complications.

Synthesis of Asymmetric 1-Thiocarbamoyl Pyrazoles as Potent Anti- Colon Cancer, Antioxidant and Anti-Inflammatory Agent.

BACKGROUND: Cancer is one of the leading diseases responsible for deaths in the society. According to the American cancer society, there will be 95,270 new cases of colon cancer in the U.S. in 2016. When a normal cell turns cancerous they develop into tumours, which produce various pro-inflammatory and inflammatory cytokines and chemokines that attract leukocytes to the site of growth. The main aim of this paper is to introduce readers about the increased number of cancer patient, effects of cancer and need of research on same. METHODS: The target molecules were prepared by reacting pyrazolealdehyde with appropriate aromatic ketone by using polyethylene glycol (PEG-300) as green solvent and catalyst to yield chalcone. Furthermore, the reaction of chalcones with thiosemicabazide yields asymmetric 1-thiocarbamoyl pyrazoles. All the newly synthesized compounds were in vitro screened for their anticancer activities against Colon SW-620 by employing the sulforhodamine B (SRB) assay method. Also all the synthesized compounds tested for in vitro antioxidant and anti-inflammatory activity by using known literature methods. RESULTS: Preliminary in vitro evaluation indicated that most of the compounds 4c, 4d and 4e possess distinct cytotoxicity profile against Colon SW-620 cell line compared to standard drug adriamycin. All the tested compounds showed good to excellent antioxidant activity against one or more reactive (H2O2, DPPH, SOR and NO) radical scavenging species. Additionally, all the synthesized compounds were screened for their in vitro antiinflammatory activity. Compounds 4a, 4b and 4e shows potent anti-inflammatory activity as compared to diclofenac sodium as a standard reference. CONCLUSION: New anti- Colon SW-620 cancer agents are the need of time, we trust that 1-thiocarbamoyl pyrazole derivatives 4c, 4d and 4e constitute an interesting template for the evaluation of new anticancer agent also antioxidant and anti-inflammatory work may provide an interesting insight for further development.

Laboratory evaluation of different formulations of Stress Coat® for slime production in goldfish (Carassius auratus) and koi (Cyprinus carpio).

A study was carried out to assess the effect of Stress Coat® on slime production in goldfish (Carassius auratus) and koi (Cyprinus carpio). The study also investigated histological changes that might be associated with slime producing cells, and wound healing in koi. Several formulations of Stress Coat® were investigated and the results showed that polyvinylpyrrolidone (PVP), also known as povidone, an ingredient of Stress Coat®, when used alone, showed significantly higher slime production in goldfish than salt and Stress Coat® without PVP after 25 h. The results also showed that koi treated with compounds containing PVP showed better wound healing than those not exposed to PVP. Histology results showed no difference between compounds tested with regards to density and number of slime producing cells.

Substituent Effect on Absorption and Fluorescence Properties of Thieno[3, 2-c]Pyridine Derivatives.

New substituted thieno[3,2-c]pyridine derivatives 5 were synthesized by the reaction of 3-bromo-4-chlorothieno[3,2-c]pyridine 1 with cyclic amine 2, which further on Suzuki reaction with boronic acids 4 converted to corresponding 3-arylthieno[3,2-c]pyridine 5. Substituent R3 has predominant effect on fluorescence properties of thienopyridines. However, the electron donor amine at C4 has no effect on fluorescence properties of thienopyridines. Graphical Abstract New thieno[3,2-c]pyridine derivatives were synthesized from 3-bromo-4-chlorothieno[3,2-c]pyridine and cyclic amines, which by on Suzuki reaction with boronic acids converted to corresponding 3-arylthieno[3,2-c]pyridine. Substituent R3 has predominant effect on fluorescence properties of thienopyridines. However, the electron donor amine at C4 has no effect on fluorescence properties of thienopyridines.

An efficient and safe process for the preparation of ticagrelor, a platelet aggregation inhibitor via resin-NO2 catalyzed formation of triazole ring.

An efficient, safe and improved process for the preparation of ticagrelor 1, a platelet aggregation inhibitor is described. Synthesis comprises the condensation of pyrimidine amine derivative 14 with cyclopentyl derivative 13 in ethylene glycol followed by construction of triazole compound 16 by diazotization of the obtained intermediate 15 with a green and safer reagent "Resin-NO2" in water and acetonitrile mixture. Condensation of 16 with cyclopropylamine derivative 10 followed by deprotection of compound 12 with hydrochloric acid in dichloromethane (DCM) furnished ticagrelor 1 with an overall yield of 65 % and purity of 99.78 % by HPLC. Each reaction stage was optimized independently to establish the scalable and plant friendly process. An efficient and a safe process for key intermediate 14 which involve nitration reaction has also been developed. Safety parameters were established by understanding the thermal events of the reaction by DSC analysis.Graphical abstractSynthesis of ticagrelor via resin-NO2 catalysed formation of triazole ring.

PEG mediated synthesis and biological evaluation of asymmetrical pyrazole curcumin analogues as potential analgesic, anti-inflammatory and antioxidant agents.

The new series of asymmetrical pyrazole curcumin analogues 4a-g were synthesized by using polyethylene glycol (PEG-400) as a green reaction medium and evaluated for their in vivo analgesic and in vitro antioxidant (H2 O2 , DPPH, Ferrous reducing power and Nitric oxide scavenging activity) and anti-inflammatory activities. All the compounds synthesized 4a-g showed the potential to demonstrate analgesic activity as compared to the standard ibuprofen. Among the tested series, compounds 4e and 4b exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT). Compounds 4b, 4d, 4f, and 4g showed good DPPH free radical scavenging activity. Compounds 4b, 4c, 4d, 4e and 4g showed excellent ferrous-reducing power activity, whereas all the compounds showed better nitric oxide scavenging activity than standard ascorbic acid. Additionally, all the synthesized compounds were also screened for their in vitro anti-inflammatory activity. Compounds 4b, 4d, 4f and 4g showed good anti-inflammatory activity as compared to standard diclofenac sodium.

Synthesis and Study the Effect of Donor-Acceptor Substituent on Fluorescence Behavior of Thieno[3, 2-c]pyridine Derivatives.

4-Hetero-1-yl-2-bromothieno[3,2-c]pyridines 3(a-d) were synthesized by the reaction of 2-bromo-4-chlorothieno[3,2-c]pyridine (1) and cyclic amine 2(a-d), which on Suzuki coupling with substituted boronic acids 4(a-f) exclusively converted to corresponding 4-hetero -1-yl-2-arylthieno[3,2-c]pyridine 5(a-x) in good yields. The effect of donor-acceptor substituent on absorption emission properties and fluorescent quantum yield of new thienopyridine derivatives 5(a-x) were studied.

Skip segment Hirschsprung's disease: a case report and novel management technique.

Skip segment Hirschsprung's disease is a condition where an area of normally ganglionated intestine is interspersed proximally and distally by aganglionic segments. The occurrence of skip segment has no clear embryological explanation, contrary to the present concept of failure of cranio-caudal migration of neural crest-derived cells in Hirschsprung's disease. Only 25 case reports have been published in literature so far and this is possibly the first to be reported from Asia. We report one such case with novel surgical management.

Successful management of a renal fungal ball in a pretermature neonate: A case report and review of literature.

Invasive fungal infection is common in the present day NICUs - generally manifesting as candiduria or candida sepsis. Fungal balls in the kidneys are very uncommon and most are amenable to higher antifungal agents. However, we had a child who did not respond to such measures and ultimately needed a surgical removal of the fungal ball in his kidney. We report this case along with a review of literature to highlight about this uncommon, but an important cause of persistent sepsis in pre-term infants and to review the treatment options including a surgical removal.

Synthetic tactics of new class of 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile derivatives acting as antimicrobial agents.

Thermal selective reactions were studied on oxothieno[2,3-d]pyrimidine-6-carboxamide 3 with POCl3 and PCl5. At 25-50 °C, the C7-amide rearranges to nitrile furnished compound 4 in 85-90% yield, while at 80-110 °C furnished mixture of products 4 and 5 in 28-68% yields. The chloro displacement with amines in compound 5 yielded 4-aminothieno[2,3-d]pyrimidine-6-carbonitrile derivatives 8(a-h) and 9(a-e). Antimicrobial activity of new compounds was studied against several bacteria such as Staphylococcus aureus MTCC-96, Escherichia coli MTCC-443, Pseudomonas aeruginosa MTCC-4 41, Streptococcus pyogenes MTCC-442 and fungi Aspergillus niger MTCC-282, Aspergillus clavatus MTCC-1323, Candida albicans MTCC-227 using broth microdilution method. Compounds 4, 8b, 8d, 8e, 8h and 9a showed promising antibacterial activity compared to ampicillin and compounds 8b, 8h showed better antifungal activity compared to greseofulvin.

PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents.

A new series of fluoro substituted pyrazoline derivatives 5a-g and 6a-g were synthesized in good to excellent yield from the corresponding pyrazole chalcones, 4a-g, by using polyethylene glycol-400 (PEG-400) as an alternative reaction medium. The newly synthesized compounds were characterized and screened for their in vivo antiinflammatory and analgesic activity. Compounds 5g and 6g were found to be more potent than standard drug Diclofenac and six other compounds 5b, 5c, 5f, 6b, 6c and 6f showed significant antiinflammatory activity as compared to standard drug. Compounds 5c, 5d, 5e, 5f, 6c, 6d, 6e and 6f showed significant analgesic activity as compared to standard drug Aspirin.

Gallbladder duplication associated with duodenal atresia.

Gallbladder duplication is an extremely rare anomaly. Association of gall bladder agenesis with duodenal atresia and biliary atresia has been described. However, association of gall bladder duplication with duodenal atresia hasn't been described so far; we report a case in view of its rarity.

Extrarenal calyces associated with pelviureteric junction obstruction: A case report of a rare anomaly.

Extrarenal calyces are one of the rare renal anomalies associated with the collecting system. Their association with renal ectopia or horse shoe kidney is known. But, here in, we are reporting an intraoperative surprise, where extrarenal calyces were associated with pelviureteric junction obstruction and routine preoperative imaging did not show any light on the diagnosis.

Heterotopic pancreas causing duodenal obstruction in a patient previously treated for choledochal cyst.

A 9-year-old boy presented with duodenal pancreatic rest causing obstruction and required surgical intervention. He had been treated at the age of 4 months for a choledochal cyst. Both choledochal cyst and heterotopic pancreas are entities that are commonly encountered in children, but the incidental presence of both the entities in the same child, albeit presenting metachronously, is extremely rare.