A comparison of intrathecal dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine for gynecological surgery

Background: Various adjuvants are being used with local anesthetics for prolongation of intraoperative and post-operative analgesia. Dexmedetomidine, a highly selective alpha2 adrenergic agonist, is a new neuraxial adjuvant gaining popularity. The purpose of this study was to compare the onset, duration of sensory and motor block, hemodynamic effects, post-operative analgesia, and adverse effects of dexmedetomidine and clonidine with hyperbaric 0.5% bupivacaine for spinal anesthesia.Methods: 60 patients belonging to ASA Grade 1 and 2 undergoing elective gynecological surgery under spinal anesthesia were studied in this prospective. The patients were allocated in two groups (30 patients each). Group bupivacaine + clonidine (BC) received 17.5 mg of bupivacaine supplemented 45 mcg clonidine and Group bupivacaine + dexmedetomidine (BD) received 17.5 mg bupivacaine supplemented 5 mcg dexmedetomidine. The onset time of sensory and motor level, time to reach peak sensory and motor level, the regression time of sensory and motor level, hemodynamic changes, and side effects were recorded.Results: Patients in Group BD had significantly longer sensory and motor block time than patients in Group BC. The onset time to reach dermatome T4 and modified Bromage3 motor block were not significantly different between two groups. Dexmedetomidine group showed significantly less and delayed requirement of rescue analgesic.Conclusion: Intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability and reduced demand of rescue analgesic in 24 hrs as compared to clonidine

Spectrophotometric and Chromatographic Simultaneous Estimation of Amitriptyline Hydrochloride and Chlordiazepoxide in Tablet Dosage Forms

A binary mixture of amitriptyline HCl and chlordiazepoxide was determined by three different methods. The first method involved determination of amitriptyline HCl and chlordiazepoxide using the first derivative spectrophotometric technique at 219 and 230 nm over the concentration ranges of 1-20 and 2-24 μg/ml with mean accuracies 100.9±0.87 and 99.2±1.0%, respectively. The second method was reversed-phase high performance liquid chromatography using methanol: acetonitrile: 0.065 M ammonium acetate buffer (50:20:30, v/v/v), final pH adjust to 5.5 ± 0.02 with ortho phosphoric acid as the mobile phase and was pumped at a flow rate of 1.0 ml/min. Quantification was achieved with ultraviolet detection at 240 nm over concentration ranges of 0.25-4 and 0.1-1.6 μg/ml; mean accuracies were 100.55±0.62 and 100.71±0.81%, respectively. The third method utilized high performance thin layer chromatography method in tablet dosage form. The method was based on separation of the two drugs followed by densitometric measurements of their spots at 240 nm. The separation was carried out on Merck thin layer chromatographic aluminium sheets of silica gel 60 F254 using carbon tetrachloride: acetone: triethylamine (6:3:0.2, v/v/v) as mobile phase. The linearity was found to be in the range of 50-600 and 20-240 ng/spot for amitriptyline hydrochloride and chlordiazepoxide, respectively. The methods were successively applied to pharmaceutical formulation because no chromatographic interferences from the tablet excipients were found. The suitability of these methods for the quantitative determination of the compounds was proved by validation

Simultaneous RP-HPLC Estimation of Trifluoperazine Hydrochloride and Chlordiazepoxide in Tablet Dosage Forms

A binary mixture of trifluoperazine HCl and chlordiazepoxide was determined using reversed-phase liquid chromatography method using methanol:water (97:03, v/v) pumped at a flow rate of 1.0 ml/min. Quantification was achieved with ultraviolet detection at 262 nm over concentration ranges of 0.1-1 and 0.5-5 μg/ml; mean accuracies were 101.05±0.47 and 98.97±0.33 %, respectively. The method was successively applied to tablet dosage forms as no chromatographic interferences from the tablet excipients were observed. The method retained its accuracy and precision when the standard addition technique was applied

Simultaneous Spectrophotometric Estimation of Imipramine Hydrochloride and Chlordiazepoxide in Tablets

A binary mixture of imipramine HCl and chlordiazepoxide was determined by three different spectrophotometric methods. The first method involved determination of imipramine HCl and chlordiazepoxide using the simultaneous equations and the second method involved absorbance ratio method. Imipramine has absorbance maxima at 251 nm, chlordiazepoxide has absorbance maxima at 264.5 nm and isoabsorptive point is at 220 nm in methanol. Linearity was obtained in the concentration ranges of 1-25 and 1-10 μg/ml for Imipramine HCL and Chlordiazepoxide, respectively. The third method involved determination of these two drugs using the first-derivative spectrophotometric technique at 219 and 231.5 nm over the concentration ranges of 1-20 and 2-24 μg/ml with mean accuracies 99.46±0.78 and 101.43±1.20%, respectively. These methods were successively applied to pharmaceutical formulations because no interferences from the tablet excipients were found. The suitability of these methods for the quantitative determination of the compounds was proved by validation

Estimation of Duloxetine Hydrochloride in Pharmaceutical Formulations by RP-HPLC Method

Simple, specific, accurate and precise method, namely, reverse phase high performance liquid chromatography was developed for estimation of duloxetine HCl in pharmaceutical formulations. For the high performance liquid chromatography method, Phenomenox C-18, 5 μm column consisting of 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.01M 5.5 pH phosphate buffer: acetonitrile (60:40 v/v) and final pH adjust to 5.5±0.02 with phosphoric acid was used. The flow rate was 1.2 ml/min and effluent was monitored at 231 nm. The retention time was 5.61 min. The method was validated in terms of linearity, accuracy and precision. The linearity curve was found to be linear over 0.25-4 μg/ml. The limit of detection and limit of quantification were found to be 0.10 and 0.25 μg/ml respectively. The proposed method was successfully used to determine the drug content of marketed formulations

A Solankee 2.pmd

ABSTRACT 2-(Substitutedphenyl/ 2"-furanyl / 2"-thienyl)-3-(2'-ethylthiophene)-4-thiazolidinones (IIa-e) have been synthesized by cyclocondensation of thioglycolic acid with different Schiff-bases (Ia-e), which in turn were prepared by the action of different aromatic and heterocyclic aldehydes with thiophene-2-ethylamine. Cyclocondensation of Schiff-bases (Ia-e) with thiolactic acid resulted 2-(substitutedphenyl / 2"-furanyl / 2"-thienyl)-3-(2'-ethylthiophene)-5-methyl-4-thiazolidinones (IIa-e). The structure of newly synthesized compounds have been confirmed on the basis of IR, 1 H NMR spectral data and physical data. Key words: Schiff-bases, thioglycolic acid, thiolactic acid, 4-thiazolidinones, spectral data. EXPERIMENTAL All melting points were determined in open capillary and are uncorrected. The IR spectra were recorded on Perkin-Elmer 237 spectrophotometer

Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin

BACKGROUND: The efficacy of flibanserin in treating hypoactive sexual desire disorder (HSDD) is based upon statistically significant improvements in sexual desire, satisfying sexual events, and distress. However, clinically meaningful benefit has not been well characterized. AIM: Evaluate clinically meaningful benefit of flibanserin. METHODS: Data were pooled from 3 pivotal trials evaluating flibanserin 100 mg qhs in premenopausal women (flibanserin, n = 1192; placebo, n = 1215). Flibanserin trial data in postmenopausal women (flibanserin, n = 450; placebo, n = 476) were analyzed separately. Clinically meaningful benefit was evaluated by the Patient Global Impression of Improvement (PGI-I). Responders were determined through anchor-based analyses that used the PGI-I for key efficacy endpoints: satisfying sexual events (SSE), desire domain of the Female Sexual Function Index (FSFI-d), and distress associated with decreased sexual desire (FSDS-R13). Odds ratios were calculated to assess effect size and Kaplan-Meier analyses were performed to estimate onset time for treatment benefit. OUTCOMES: PGI-I, anchor-based analyses for key efficacy endpoints (SSE, FSFI-d, FSDS-R13), odds ratios, onset time for treatment benefit. RESULTS: Based on the PGI-I, more patients reported clinically meaningful benefit with flibanserin treatment versus placebo (49.8% vs 33.6%, premenopausal cohort; 40.5% vs 28.7%, postmenopausal cohort). In anchor-based analyses, responder rates were significantly higher for premenopausal women on flibanserin (46.1%-55.2%) than placebo (34.1%-44.2%) for all 3 key efficacy endpoints (P \u3c .0001). Responder rates for postmenopausal women on flibanserin were higher compared to placebo for SSE (29.8% vs 22.9%; P = .015) and FSFI-d (38.9% vs 26.3%; P = .0001). Odds ratios for key endpoints indicated that premenopausal women were 2.0-2.4 times as likely to be responders with flibanserin treatment compared to placebo. Postmenopausal women were 1.6 times as likely to be responders with flibanserin for FSFI-d. Kaplan-Meier analyses indicated significant separation between flibanserin and placebo for the key endpoints in both premenopausal and postmenopausal cohorts (log-rank tests P \u3c .01) with earlier median response times among patients receiving flibanserin. CLINICAL IMPLICATIONS: Patient-reported benefit assessments such as the PGI-I capture the patient\u27s perspective and may be a useful approach in assessing overall clinical meaningfulness for sexual dysfunction therapies. STRENGTHS AND LIMITATIONS: Strengths include a well-powered study with large enrollment, use of validated instruments, and self-assessment of treatment benefit. Limitations include pooling of trial data in premenopausal women with slightly different study designs and use of an endpoint (SSE) indirectly related to HSDD. CONCLUSION: Assessment of clinically meaningful benefit and additional responder analyses provide further support for flibanserin\u27s efficacy beyond numerical improvements in endpoint measures. Simon JA, Clayton AH, Kim NN, et al. Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin. Sex Med 2022;10:100476

Yogesh Prajapat 1.pmd

ABSTRACT Chalones, 2,4-bis-(4'-flurophenylamino)-6-[4'-{3"-(substituted phenyl/2"'-furanyl)-2"-propenon-1"-yl} phenylamino] s-triazine (6a-e) have been prepared from ketone (5) on treatment with different aromatic/hetarocyclic aldehydes. These chalcones on cyclisation with guandiine nitrate in presence of alkali and malononitrile in presence of ammonium acetate give the corresponding aminopyrimidine (7a-e) and cyanopyridine (8a-e) derivatives respectively. All the synthesized compounds have been screened for their antibacterial activity against S. aureus (MTCC 96), B. subtilis (MTCC 441), E. coli (MTCC 443) and S. paratyphi-B. (MTCC 733). The structure of the synthesized compounds have been established on the basis of their elemental analysis and spectral studies

Trisomy 8 in leukemia: A GCRI experience

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005-September 2008). Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML) (36), acute myeloid leukemia (AML) (17), and acute lymphoblastic leukemia (ALL) (7). In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22), t(15;17), and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered