P. Pratap Reddy

Elective Surgery for Corrosive-Induced Gastric Injury

Abstract. Gastric cicatrization is a well recognized late sequela of corrosive gastric injury, but the optimum timing and type of surgery for this complication are still unclear. Over a 7-year period (1988–1994) 34 patients underwent elective surgery for gastric lesions secondary to corrosive ingestion. A total of 18 (53%) patients had an associated esophageal stricture and presented with dysphagia, 15 (44%) patients had features of gastric outlet obstruction, 6 (18%) had diffuse gastric injury, and 28 (82%) had a segmental lesion. A tube jejunostomy was done in 23 (68%) patients to improve nutrition and resulted in a significant increase in weight and in the serum protein level after 8 weeks of tube feeding. Elective surgery was performed 3 to 24 months (average 7 months) after ingestion of the corrosive substance. Gastric resection was done in 20 (59%) patients and gastrojejunostomy (without vagotomy) in 11 (32%); at follow-up the latter group did not exhibit development of a stomal ulcer. In patients with an associated esophageal stricture, endoscopic dilatation was successful in 89% patients and simplified the surgical approach. In conclusion, the success of surgery for corrosive-induced gastric injury depends on selecting the right procedure and intervening at the appropriate time.

Tumour necrosis factor alpha and interleukin 10 gene polymorphisms and the risk of ischemic stroke in south Indian population.

Stroke is the leading cause of adult disability and mortality and is the third largest cause of death worldwide (Bonita et al. 2004). Prevalence of stroke in India varies in different regions of the country and ranges from 40 to 270 per 100,000 population (Anand et al. 2001). Both environmental and genetic factors are involved in the causation of strokes (Bevan and Markus 2004). Cytokines play an important role in immune response and also maintain the normal homeostatic environment of the central nervous system. The key phenomenon in cytokine contribution to ischemic stroke is endothelial transformation altering hemostatic and immunological balance towards the prothrombotic and proinflammatory states (Ross 1993). The genes encoding diverse cytokines may play a vital role in the susceptibility to stroke, and the production of cytokine varies among individuals and depends on cytokine gene polymorphisms. The present study was carried out to evaluate the association of tumour necrosis alpha (TNFα) -308G/A and interleukin (IL) 10-1082G/A polymorphisms with ischemic stroke in south Indian population and the results showed that the IL-10 ‘GG’ genotype is significantly associated with stroke.

Identification, synthesis, isolation and spectral characterization of potential impurities of montelukast sodium

During the process development of montelukast sodium, three polar impurities and one non-polar impurity with respect to montelukast sodium were detected by simple reverse phase high-performance liquid chromatography (HPLC). Initially, all the four impurities were identified by the liquid chromatography-mass spectrometry (LC-MS) data and out of four impurities, three have been prepared by the synthetic method and remaining one is isolated by preparative HPLC. Based on the spectral data (IR, (1)H NMR, (13)C NMR and MS), the structure of these impurities 1-4 were characterised as 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetamide (impurity-1), {1-[1-{3-[2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-3-(2-isopropenyl-phenyl)-propylsulfanylmethyl]-cyclopropyl}-acetic acid (impurity-2), 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-3) and 1-[[[(1R)-1-[3-[(1E)-2-(2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-4).

Rheolytic thrombectomy for dural venous sinus thrombosis.

Cerebral venous thrombosis is a rare condition. Its diagnosis and management can be difficult. Treatment options include systemically delivered anticoagulation or thrombolysis. Intrasinus thrombolysis is an increasingly used intervention but it increases the risk of hemorrhage, especially in patients who have a rapidly deteriorating neurological condition. Mechanical thrombectomy that provides rapid canalization without increased risk of hemorrhage is an attractive alternative treatment.

New Synthesis of Analogues of the Antihypertensive Active Pharmaceutical Ingredient Irbesartan

Abstract A simple and new synthetic approach to various analogues of Irbesartan is described. DRL Pub. No. IPDO‐IPM 00018

UNEXPECTED FORMATION OF CYCLIC HYDROXAMIC ACIDS FROM O-(2-AMINOBENZOYL) HYDROXYLAMINE

Abstract Cyclic hydroxamic acids 3 and 4 are the unexpected products in the reaction of 0-(2-aminobenzoyl) hydroxylamine 1 and orthoesters, acid chlorides, ethyl chloroformate.

Synthesis of Valganciclovir Hydrochloride Congeners

Abstract Valganciclovir hydrochloride (1) is used for the treatment of cytomegalovirus (CMV) retinitis in patients with weakened immune systems. Valganciclovir hydrochloride is a hydrochloride salt of L-valyl ester of ganciclovir (2) that exists as a mixture of two diastereomers. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. During the process development of valganciclovir hydrochloride, six related substances (impurities) were observed along with the final active pharmaceutical ingredient. Among these six impurities, ganciclovir (2) and guanine (3) are the key starting materials and degraded impurities of ganciclovir, respectively. The remaining four impurities were identified as isovalganciclovir hydrochloride (4), methoxymethylguanine (5), O-acetoxy ganciclovir (6), and isovalarylganciclovir (7). The present work describes the synthesis and characterization of these four impurities. GRAPHICAL ABSTRACT

New and Practical Synthesis of Montelukast Sodium, an Antiasthmatic Drug

Abstract A new and practical synthesis of montelukast sodium, an antiasthmatic drug, is described. The key steps are the synthesis of nitrile derivative 4 by chiral reduction of keto ester 9 using (−)-DIP-Cl, synthesis of vinylquinoline framework 16 by Wittig reaction, and Heck coupling of nitrile 4 with vinylquinoline 16. The method is operationally simple and suitable for the industrial production of the drug substance. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

Postnatal Risk Factors of Congenital Hearing Impairment: Otitis Media, Head Injuries and Convulsions

Abstract Hearing impairment is the most prevalent sensory disability and is caused by a variety of genetic and environmental factors. Many studies have proposed otitis media, head injury, convulsions, respiratory problems and infections to the infants as the important antecedents of neonatal deafness or hearing impairment. A prospective etiological study of adverse postnatal conditions leading to bilateral sensorineural neonatal hearing impairment was conducted. In this study 1076 children below 14 years of age with congenital hearing loss were investigated. The results showed adverse postnatal history in 20.26% (218) of the cases out of 1076. High risk factors included otitis media, head injury and convulsions and respiratory distress. Majority (126/11.71%) of the cases showed otitis media followed by head injury in 4.83% (52) of the cases, convulsions in 2.78% (30) of the cases and respiratory problems in 0.92% (10) of the cases. It can be concluded that careful monitoring of the child during the first few years and vaccination against all the infections is necessary.

Synthesis and Characterization of Related Compounds of Aripiprazole, an Antipsychotic Drug Substance

Abstract Three related compounds of aripiprazole were identified during the synthesis. These related compounds were synthesized and characterized by their respective spectral data.