Docking studies of few substituted 5-benzyl-2, 4-thiazolidinedione with PPAR-γ for antidiabetic activity

Docking studies of few substituted 5-benzyl-2, 4-thiazolidinedione moiety, which acts as peroxisome proliferator-activated receptor γ agonist was performed by using Glide v4.5. The docking studies reveal hydrogen bond formation to Thr241 with Gscore -7.22 and energy -62.2 kcal/mole. We found hydrogen bond formation of most of compounds with good Gscore and low energy as compared to the most active rosiglitazone.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Hairy cell leukemia : experience at a tertiary cancer centre in Northern India

Background : The prognosis of Hairy cell leukemia (HCL) has improved markedly following treatment with cladribine (2- CdA), a nucleoside analogue. We reviewed data on patients with HCL treated in our department. Methods . Between 1995 and 2004, 23 patients with hairy cell leukemia (HCL) were diagnosed Patients median age was 48.5 years (range, 32 to 66 years), there were 18 males and 5 females. The common presenting symptoms were: fatigue (82.6%), fever (34.7%), abdominal discomfort (21.7%), arthralgia/bone pains (13%) and bleeding (17.3%). 22 of 23 (95.6%) patients had enlarged spleen, and hepatomegaly (65%). Lymph node enlargement was present in 17% of patients. Investigations revealedmedian Hb of 7.8g% (5.7 to 12.9 g%), thrombocytopenia (median 55000/cmm) and median WBC count of 3500/cmm (range, 600 to 20,200/cmm). Bicytopenia or pancytopenia was present in 87% and bone marrow fibrosis in 75% of cases. Immunophenotyping studies revealed expression of CD11C (60%), CD25 (60%), FMC7(47.8%), CD23(34.8%), CD103 in 39% of cases. 20 of 23 patients received treatment; two received treatment else where and one patient died of liver failure prior to treatment. 17 of 20 patients were treated with 2-CdA, 2 with interferon alfa (IFN-a) and one patient underwent splenectomy alone. Three patients received 2-CdA as second line therapy for treatment of relapse: this includes . one patient each, treated with IFN- α and splenectomy both and one patient received 2-cdA twice in view of relapse. Results . Following treatment with 2CdA . 95% of patients responded; complete-84.2% and partial response in 10.5%. one (5.2%) patient died of toxicity. Two patients relapsed at a mean follow up of 25 months. The common side effects were febrile episodes (n=10) and grade I-II myelosuppression. One patient died of toxicity to 2-CdA. This patient was a known case of multidrug resistant disseminated tuberculosis. He had severe myelosuppression with fungal sepsis with multiorgan failure and BM Aspirate was positive for AFB. Other infections documented were Pulmonary tuberculosis in 2 and herpes zoster in one patient. The patient who underwent Splenectomy achieved remission but relapsed after 3 years and was salvaged with 2-CdA again. Median time for normalization of blood counts after 2-CdA was 28 days and median time to regress spleen was 41.5 days . Conclusion . Present study confirms good outcome with 2-CdA (cladribine) therapy for patients of hairy cell leukemia

Quantitative structure activity relationship studies of some 5-aryl thiazolidine-2, 4-diones as antidiabetic agents

Quantitative Structure Activity Relationship (QSAR) studies were carried out for a series of 16 compounds which acts as ligands for PPAR-γ receptor. TSAR software was used to identify the essential structural and physicochemical features for their PPAR-γ agonistic activity by performing multiple regression analysis. Significant correlation coefficients (q² = 0.9178) was obtained. The predicted values are in good agreement with the observed activity, suggesting that the model could be useful in the design of novel, more potent PPAR-γ agonist.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of pulmonary infiltrates in patients with haematological malignancies using fibreoptic bronchoscopy and bronchoalveolar lavage

Background : Chest infection is the major cause of morbidity and mortality among patients with haematological malignancies. Conventional diagnostic methods - chest x-ray , blood and sputum culture have limited yield . We used fibreoptic bronchoscopy and bronchoalveolar lavage to evaluate nature of pulmonary infiltrates on chest x-ray. Patients and Methods : 25 patients with haematological malignancies with fever and pulmonary infiltrates were studied. Patients median age was 32 years, ranging from 16 to 65 years. There were 21 males and 4 females. Initial evaluation included - detailed physical examination including chest to see for any focus of infection. In all patients , base line blood counts (total and differential), chest x-ray and cultures from blood and other body fluids were taken before starting broad spectrum antibiotics . Those not responding over next 48-72 hours received gram positive coverage followed by amphotericin-B therapy . Patients with persistent fever and pulmonary infiltrates were subjected to fibre-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) and samples were collected for bacterial, fungal, AFB and viral studies. The findings were correlated with Chest x-ray and CT scan. Results The median time for FOB and BAL was 16 days (range, 3 to 32 days) after the clinical diagnosis of chest infection.. BAL fluid examination/culture grew microbial isolates in 21 of 25 patients (84%). Of thesebacteria alone were present in 10, fungi alone in 1 and polymicrobial isolates were seen in 10 patients (40%). Later included- a combination of bacteria and fungi - in 2 patients, bacteria and AFB - 6 and a combination of bacteria, AFB and fungi were seen in 2 patients. BAL changed the radiological diagnosis in 14 patients (56% diagnostic utility). Therapy was modified according to BAL results in 6 patients (therapeutic utility of 24 %). Concordance between radiological and BAL findings were found only in 5 patients (20%). FOB procedure was tolerated well, with mild and reversible complications (throat pain, transient hypoxia, tachycardia) in some patients. Conclusions: Infections are the main cause of pulmonary infiltrates in patients with haematological malignancies. Bacterial , fungal and mycobacterium tubercular organisms are the main isolates. Isolation of ESBL positive organisms and polymicrobial isolates suggest inclusion of appropriate initial empirical antibiotics in these patients to prevent development of resistant organisms. Higher frequency of AFB isolates (32%) was the surprising finding and need to be confirmed in future studies

A randomized, prospective open labeled study of oral amoxicillin-clavulanate and levofloxacin with intravenous ceftriaxone and amikacin in chemotherapy induced low risk febrile neutropenia

Background : We compared the efficacy of oral antibiotics with intravenous antibiotics in low risk febrile neutropenia. Design : A prospective, randomized study Methods: Between April 2004 - December 2005, 55 patients with low risk febrile neutropenia (expected neutropenia duration < 7 days with no co-morbid features) between 15 and 75 years of age, were randomized to receive either oral amoxicillin-clavulanate 625mg twice daily and levofloxacin -500mg once daily OR intravenous (i.v.) ceftriaxone 2g and amikacin 15mg/kg once daily. Most patients were treated on out patient basis. The primary end point was response to therapy, defervescence of fever within 72 hours with improvement in any clinical manifestation of infection and no recurrence of fever for 48 hours without use of antipyretics. Use of growth factors was not permitted except in treatment failure. Results: A total of 64 febrile episodes were recorded (mean 1.20 ); 33 in the IV group and 31 in the oral antibiotics group. Both groups were equally matched for age (median 25 years in the IV group and 19 years in the oral group), gender, type of cancer, baseline absolute neutrophil count (median 200/cmm in both arms) and duration of neutropenia (5 days and 4 days in the IV and oral groups, respectively). A focus of infection was identified clinically in 15% of episodes and microbiologically in 11% of episodes; 57% of which were Gram positive organisms and the rest Gram negative. 72% in the IV arm and 77% in the oral arm responded to therapy (p=ns). One patient in IV group had one episode of seizure. Non-responding patients received second line IV antibiotics. There was no mortality in either group. Age > 60 years, neutropenia lasting > 7 days after the onset of fever and positive blood culture were predictors for lack of response to antibiotics on multivariate analysis. Conclusion: Oral antibiotics have comparable efficacy as IV antibiotics in the management of low risk febrile neutropenia

A Dynamic Image Analysis Method for Fragmentation Measurement in Blasting

188-201Fragment size optimization with selection of best values of blast design variables is an important process in mine-mill fragmentation system to maximize the system performance. This calls for measurement and analysis of mean fragment size with respect to blast design parameters. Digital image analysis technique is the most accepted method for measurement of blasted fragment sizes and their distribution. For quick assessment of the fragment sizes, a new novel method based on the digital images extracted from a blast video is reported in this paper. Correction factor for the size of fragments, considering the face movement is also proposed. The method has been tested with the help of seven blast data sets. The proposed dynamic image analysis technique can not only be used in fragment size estimation but also to assess the time-progressive size reduction in a blast, which can help designing the delay timing. Further, a possibility to estimate the in-situ block size is also explored with this method. The images of blast fragmentation were extracted from their videos at an interval of 0.08 s. These images were analyzed later for measurement of mean fragment size at respective times. The fragment size of the complete muck generated by the blast was also measured and correlated well with the sizes achieved from video analysis. The analysis revealed that from 0.08 s to 0.56 s from the initiation of the blasts, the fragment size reduction progressed from 58% to 80% of the estimated in-situ rock block sizes. Significant effect of blast design variables and two firing patterns on the mean fragment size was also observed. The analysis suggested that V-type firing pattern provides finer fragment size in comparison to the diagonal firing pattern. The suggested method provides an easy yet fast way for the assessment of blast fragment size

Neoadjuvant chemotherapy followed by surgical cytoreduction in advanced epithelial ovarian cancer

Aim: To study the role of neoadjuvant chemotherapy (NACT) followed by surgical cytoreduction in the management of advanced epithelial ovarian cancers. Materials and Methods: A retrospective analysis of 82 patients with advanced epithelial ovarian cancers (stage IIIC and IV) who were treated with NACT followed by surgical cytoreduction between 1995 and 2004 was performed. Response to NACT, optimal cytoreduction rate, disease-free survival and overall survival were analyzed. Results: There were 59 patients (72%) with stage IIIC disease and 23 (28%) with stage IV disease. Diagnosis was established by imaging, ascitic fluid cytology and CA-125 estimations in 75% and by laparotomy in 25% of the patients. After NACT, complete response occurred in 17 patients (20.7%), 50 (61.0%) had partial response and no response was documented in 15 (18.3%) patients. Optimal surgical cytoreduction could be achieved in 72% of the patients. At the median follow-up of 34 months (range 6-102 months), 5-year disease-free and overall survivals were 31 and 32% respectively. The median disease free interval was 25.4 months. On multivariate analysis, degree of optimal cytoreduction was the only factor ( P <0.05) affecting survival. Conclusions: NACT followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. A significant number of patients exhibit response to NACT. Downstaging following NACT leads to higher optimal cytoreduction rates and improved survival in comparison to historical controls

Neoadjuvant chemotherapy followed by surgical cytoreduction in advanced epithelial ovarian cancer

AIMS: To study the role of neoadjuvant chemotherapy (NACT) followed by surgical cytoreduction in the management of advanced epithelial ovarian cancers. MATERIALS AND METHODS: A retrospective analysis of 82 patients with advanced epithelial ovarian cancers (stage IIIC and IV) who were treated with NACT followed by surgical cytoreduction between 1995 and 2004 was performed. Response to NACT, optimal cytoreduction rate, disease-free survival and overall survival were analyzed. RESULTS: There were 59 patients (72%) with stage IIIC disease and 23 (28%) with stage IV disease. Diagnosis was established by imaging, ascitic fluid cytology and CA-125 estimations in 75% and by laparotomy in 25% of the patients. After NACT, complete response occurred in 17 patients (20.7%), 50 (61.0%) had partial response and no response was documented in 15 (18.3%) patients. Optimal surgical cytoreduction could be achieved in 72% of the patients. At the median follow-up of 34 months (range 6-102 months), 5-year disease-free and overall survivals were 31 and 32% respectively. The median disease free interval was 25.4 months. On multivariate analysis, degree of optimal cytoreduction was the only factor ( P < 0.05) affecting survival. CONCLUSIONS: NACT followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers. A significant number of patients exhibit response to NACT. Downstaging following NACT leads to higher optimal cytoreduction rates and improved survival in comparison to historical controls