IN SILICO MODELLING, SYNTHESIS, AND ANTI-DIABETIC EVALUATION OF BENZOTHIAZOLE SUBSTITUTED OXADIAZOLE DERIVATIVES

Objective: The study contemplates in silico modeling, synthesis and in-vitro anti-diabetic evaluation of benzothiazole substituted oxadiazole derivatives. [{5-[(1, 3-benzothiazol-2-ylsulfanyl) methyl]-1, 3, 4-oxadiazol-2-yl} sulfanyl) methyl] derivatives were synthesized by a conventional method. Methods: All the newly synthesized derivatives were characterized by determining their melting point, retention factor from thin-layer chromatography, and spectral methods (Infrared, 1H NMR spectroscopy, 13C NMR spectroscopy, Mass spectroscopy) and evaluated for their anti-diabetic activity. Results: [{5-[(1, 3-benzothiazol-2-ylsulfanyl) methyl]-1, 3, 4-oxadiazol-2-yl} sulfanyl) methyl] derivatives have been made and characterized using physical and spectral methods. The in-vitro anti-diabetic screening study revealed that BZT1 and BZT4 exhibited high inhibition against glucose uptake assay and alpha-amylase enzyme. But only the derivative BZT4 showed inhibition against alpha-glucosidase enzyme. Conclusion: Various benzothiazole substituted oxadiazole derivatives were synthesized, characterized by spectral studies. The anti-diabetic studies revealed that the synthesized derivatives have significant anti-diabetic properties and further structure-activity relationship studies may develop more potent and less toxic molecules

IN SILICO DESIGN OF BENOXAZOLE BEARING AZETIDINONE DERIVATIVES AS VEGFR-2 AGONIST IN CANCER

Objective: Cancer is a group of disease characterized by uncontrolled growth of cells. The objective of the study includes the in silico designing of benzoxazole bearing azetidinone derivatives as Vascular Endothelial Growth Factor 2 in cancer. Methods: In silico design of proposed derivatives was conducted using tools such as AutoDock Vina, ACD Lab ChemSketch ver. 12.0, Prediction of Activity Spectra for Substances online, molinspiration, and Swiss ADME. The derivatives obeying Lipinski’s Rule of Five in accordance with molinspiration were selected for docking studies. Results: The data obtained from molinspiration revealed that the designed derivatives have physical and chemical properties meant for an orally bioavailable drug. From the docking studies derivatives BT1 and BT5 showed high docking score which indicate that these derivatives possess high affinity and high polar interaction towards protein 4DBN. Conclusion: The designed benzoxazole bearing azetidinone derivatives were found to possess good binding affinity and good interaction in the binding pocket of the target 4DBN. Therefore, these derivatives are expected to exhibit good anticancer property with minimal side effects

AZATHIOPRINE INDUCED PANCYTOPENIA-A CASE REPORT

Azathioprine (AZA), a prodrug of 6 mercaptopurine, is an immunosuppressant that can be used as adjunctive therapy with corticosteroids in the treatment of arteritic form of ischemic optic neuropathy. Although myelotoxicity is known to occur while using azathioprine, severe pancytopenia is rarely seen. Patients with thiopurine methyltransferase (TPMT) deficiency are at high risk of developing severe myelosuppression. A 63 year* old female with ischemic optic neuropathy was initiated treatment with oral methylprednisone. As two courses of oral steroids showed no significant improvement, oral azathioprine 25 mg twice daily was added and gradually increased to 50 mg twice daily with relief of symptoms. 6 mo later, she was admitted with acute stroke and lab reports showed low levels of total blood counts or pancytopenia. The patient was put on broad spectrum antibiotics; given injection of granulocyte colony stimulating factor 300 mcg subcutaneously and blood transfusion as correction till counts normalised. She improved over 14 d and on next follow-up counts were in normal range. Causality was assessed by Naranjo causality assessment scale and a probable relationship was obtained between azathioprine and pancytopenia with a score of 6. Variations in TPMT activity occurs due to genetic polymorphism. Physicians should be aware of the possibility of myelosuppression while prescribing azathioprine. Frequent blood count monitoring is the most convenient way to avoid this problem where testing for TPMT deficiency is not possible

STUDY ON QUALITY OF LIFE ASSESSMENT IN DIABETIC RETINOPATHY AMONG PATIENTS WITH TYPE 2 DIABETES

Objective: The aim was to study the vision-related quality of life (QOL) for diabetic retinopathy (DR) among patients with Type 2 diabetes and to assess the direct medical cost of different treatment modalities. Methods: It was based on an individual-based analysis of QOL before and after the treatment for DR. The main objective of the study was to compare QOL between patients based on the different treatment modalities using vision function questionnaire (VFQ)-25, to evaluate the direct medical cost for DR patients undergoing different treatment modalities and to compare the cost and QOL of different treatment modalities in samples with non-proliferative DR (NPDR)/proliferative diabetic retinopathy (PDR) macular edema. The population included were patients with Type 2 diabetes with NPDR, with clinically significant macular edema and PDR, patients diagnosed to have diabetes above 5-year duration, adult patients, ocular pain those who are on regular follow-up and those who are willing to be a part of study. A total of 256 patients were selected out, of which 141 patients were satisfied the study criteria and participated in the study. Data relevant to the voice-related QOL study were obtained and recorded using VFQ-25 questionnaire. Other data relevant to the study were obtained and recorded in a semistructured data collection form by interviewing the patient or their caregivers and by direct examination of patient's medical record. Expenditure was calculated in Indian Rupees. Results: After comparing the baseline QOL with QOL after treatment, it was found that the overall QOL of the study samples in accordance with the treatment undergone was found to be improved. The overall QOL had improved after the treatment for all samples and major improvement was seen on dependency, social functioning (SF), and mental health (MH). Conclusion: The overall QOL had improved after the treatment for all samples and major improvement were seen on dependency, SF, and MH. In conclusion, the study analyzed that intravitreal bevacizumab therapy is the cheapest one and with the comparatively same clinical outcome when compared with intravitreal ranibizumab therapy for macular edema cases in patients with NPDR and PDR

CASE REPORT ON DOCETAXEL-INDUCED INTERSTITIAL LUNG DISEASE

  Docetaxel belongs to taxane family of antineoplastic agents that are indicated for the treatment of locally advanced or metastatic non-small-cell lung cancer. Docetaxel is associated with many adverse effects, and pulmonary reaction has an incidence of 41%. However, interstitial pulmonary disease is found to occur only in <1% of the population as per the post-marketing surveillance reports. Here, we report a case of docetaxel-induced interstitial lung disease (ILD). The patient information and details were collected using the hospital information system. The adverse drug reaction (ADR) of ILD occurred after 5 cycles of chemotherapy with docetaxel at a dose of 60 mg/m2 that is 80 mg IV. The causality of the event in our case was assessed using the Naranjo ADR probability scale which marked a score of 7 (probable). It is necessary that all physicians be aware of the reaction and to closely monitor clinicoradiological and functional status of the patients at regular intervals after administration of docetaxel

CARBAMAZEPINE-INDUCED TOXIC EPIDERMAL NECROLYSIS: A CASE REPORT

Toxic epidermal necrolysis (TEN) is a life-threatening dermatological disorder characterized by erythematous lesions, necrosis, exfoliation, sepsis, and death. This may be due to different reasons such as chemical exposure, systemic infections, or some reactions of drugs such as carbamazepine, phenytoin, allopurinol, lamotrigine, and nonsteroidal anti-inflammatory drugs. In this case, the patient was on carbamazepine for the management of alcohol withdrawal symptoms. Moreover, this might be the reason for the occurrence of TEN. For his condition, he had given corticosteroids, antibiotics for sepsis, and other supportive measures

A CASE SERIES ON ANTI NMDAR ENCEPHALITIS

N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune neurological disorder arising from the generation of antibodies which binds to the synaptic proteins. Here we present a case series of 3 cases where the different aspects of treating NMDAR encephalitis are dealt with. The association of ovarian teratoma and the importance of its removal before treating the encephalitis have been discussed in the second case. Apart from the first line and second line agents used in the therapy of NMDAR encephalitis, the importance of managing infections especially urinary tract infection and lower respiratory tract infection with antibiotics have also been discussed. The article also aims to throw light into the treatment of extrapyramidal side effects induced by antipsychotics. At the end, the significance of putting the patient on a ketogenic diet to manage refractory seizures associated with anti-NMDA receptor encephalitis has also been discussed based on reviewing literature

A retrospective analysis of patients treated with intravesical BCG for high-risk nonmuscle invasive bladder cancer

Background: Adjuvant intravesical immunotherapy with Bacillus Calmette–Guerin (BCG) is considered as the first-line agent in patients with high-risk nonmuscle invasive bladder cancer (NMIBC) after surgery. There are no data in India where there is a high prevalence of tubercle bacillus and inherent immunity against Bacillus sp. The present study aims to evaluate the outcomes of intravesical BCG in the Indian population. Methods: A retrospective study of 101 patients who underwent intravesical BCG for high-risk NMIBC between January 2006 and December 2015 was carried out in a single centre. We compared the recurrence-free rate and progression rate of patients who received induction alone and induction with maintenance BCG therapy. The safety profile of intravesical BCG therapy was also assessed in the study. Results: After a median follow up of 2 years, the disease-free survival (DFS) rates of the induction group and maintenance group were 82% and 88% respectively ( p = 0.233). There was no difference in progression-free survival (PFS) rates at 2 years in those who receive maintenance BCG (95%) and those with induction BCG (94.7%; p = 0.721). A total of 69.36% of our patients had local adverse events. Conclusion: Our results suggest that maintenance therapy does not enhance the therapeutic effects of BCG in patients who respond favourably to 6 weeks of induction. Additional prospective studies are warranted in those countries where tuberculosis exposure is prevalent

AZATHIOPRINE INDUCED PANCYTOPENIA-A CASE REPORT

Azathioprine (AZA), a prodrug of 6 mercaptopurine, is an immunosuppressant that can be used as adjunctive therapy with corticosteroids in the treatment of arteritic form of ischemic optic neuropathy. Although myelotoxicity is known to occur while using azathioprine, severe pancytopenia is rarely seen. Patients with thiopurine methyltransferase (TPMT) deficiency are at high risk of developing severe myelosuppression. A 63 year* old female with ischemic optic neuropathy was initiated treatment with oral methylprednisone. As two courses of oral steroids showed no significant improvement, oral azathioprine 25 mg twice daily was added and gradually increased to 50 mg twice daily with relief of symptoms. 6 mo later, she was admitted with acute stroke and lab reports showed low levels of total blood counts or pancytopenia. The patient was put on broad spectrum antibiotics; given injection of granulocyte colony stimulating factor 300 mcg subcutaneously and blood transfusion as correction till counts normalised. She improved over 14 d and on next follow-up counts were in normal range. Causality was assessed by Naranjo causality assessment scale and a probable relationship was obtained between azathioprine and pancytopenia with a score of 6. Variations in TPMT activity occurs due to genetic polymorphism. Physicians should be aware of the possibility of myelosuppression while prescribing azathioprine. Frequent blood count monitoring is the most convenient way to avoid this problem where testing for TPMT deficiency is not possible

Crizotinib, an Effective Agent in -Rearranged Adenocarcinoma of Lungs: A Case Report

Introduction: ROS1 rearrangement has recently emerged as a new molecular subtype in non–small-cell lung cancer (NSCLC) and is predominantly found in lung adenocarcinoma compared with other oncogenes such as EGFR, KRAS , or ALK . It has been identified in only 1% to 2% of NSCLC cases. Case Report: We report a case of 52-year-old man (nonsmoker) with a medical history of allergic rhinitis and bronchial asthma. Histopathologic examination of bronchoscopic-guided biopsy showed adenocarcinoma histology on September 2015. After 2 months, he developed left-sided pneumonia for which he was treated with multiple intravenous antibiotics. In the meantime, fiberoptic bronchoscopy was done which revealed purulent secretion from right upper lobe and narrowed opening of right middle lobe. His cancer symptoms got worsened and bronchial biopsy showed EGFR mutation negative. For further diagnosis, fluorescent in situ hybridization test was done which showed ROS1 mutation positive. By then, the patient was started with crizotinib 250 mg twice daily for ROS1 mutation in July 2016. Later, patient appears to benefit from treatment with crizotinib. X-ray report and positron emission tomographic-computed tomographic scan revealed that the patient was overall better with clear chest and well tolerated with the therapy. Crizotinib was approved on March 11, 2016 by Food and Drug Administration for the treatment of patients with ROS1-positive NSCLC. Conclusions: In this report, crizotinib showed marked antitumor activity in patients with advanced ROS1 rearrangement, a third molecular subgroup of NSCLC