SIMULTANEOUS METHOD FOR THE ESTIMATION OF BEDAQUILINE AND DELAMANID IN HUMAN PLASMA USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

Objective: A specific, simple and sensitive high-performance liquid chromatographic method for the estimation of Bedaquiline (BDQ) and Delamanid (DLM) in human plasma was developed. Methods: The method involved deproteinization and further extracted the analyte using Solid Phase Extraction (SPE) cartridge and analysed using C18 column with the wavelength set at 231 nm. The isocratic mobile phase consisted of 10 mmol ammonium acetate buffer containing 0.25% acetic acid and 0.02% trifluoroacetic acid and acetonitrile in the ratio of 20:80(v/v). The validation parameters were evaluated. The method was applied to estimate plasma BDQ and DLM collected from five MDR-TB patients. Results: Well resolved peaks of BDQ and DLM at retention times of 5.4 and 2.6 min were obtained respectively. The calibration curve was linear over a range of 0.01–10.0 µg/ml for both BDQ and DLM. The intra-and inter-day relative standard deviations for standards were below 10%. The recoveries for BDQ ranged from 101% to 107% and 98% to 107 % for DLM respectively. Conclusion: A specific and sensitive method for simultaneous determination of BDQ and DLM in plasma using high-performance liquid chromatography was developed. This method can be used in clinical studies to evaluate drug exposure

Facile approach of enhanced heat mitigation between 3D stacked layers by Introducing a sub-micron thick heat spreading materials

Polder and Van Hove in 1971 forecasted, it is possible to transfer heat between the planer surface by phonon tunneling mechanism, having interlayer separation that is comparable to the phonon wavelength. Towards that, in this work we examined the heat mitigation issues widely prevalent in 3D stacked ICs using finite element analysis. We observed batter heat mitigation by using optimized thickness of heat spreader sandwiched between ICs, containing TTSVs. FEM result shows nearly 15 oC reduction in temperature from 313oC to 298 oC of the top most IC in a 3D stack compared with the case without TTSV and heat spreader in the ILD plane

Pharmacokinetics of isoniazid and rifampicin in patients with renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD) Running Head : Pharmacokinetic of INH & RMP in renal failure (CAPD)

The pharmacokinetics of isoniazid (INH) and rifampicin (RMP) was determined in 22 renal failure patients, 11 each with low and high membrane permeabilities (LMP and HMP) undergoing Continuous Ambulatory Peritoneal Dialysis (CAPD). Blood samples were collected at different time points following oral administration of INH and RMP. Estimations of INH and RMP in blood were carried out by standard procedures and certain pharmacokinetic variables were calculated based on their concentrations in blood. The INH inactivation status was determined based on salivary levels of INH. The pharmacokinetic variables of INH and RMP did not differ significantly between LMP and HMP groups. The study results suggest that renal failure patients on CAPD may not require reduction in the dosage of RMP or INH in rapid acetylators. Slow acetylators might require dose reduction of INH. Determination of INH inactivation status is important when patients with renal failure and tuberculosis are treated with INH-containing regimens

Role of USG in thyroid diseases

One of the most distinctive glands in the body is the thyroid gland. It is the only gland in the body that gets its iodine directly from outside sources, making it unique among glands. It is the only gland in the body that is able to make, store, and expel its own products when the body has a need for those goods. It has a very abundant blood supply that can be compared to that of the kidneys. Additionally, it is the only gland that can be compared to that of the kidneys. Therefore, the regulation that it has is extraordinary. It is quite superficially situated, and as a result, high frequency probes may be utilised to study it with relative ease. There have been investigations in which a straightforward transvaginal probe served as an effective research tool for examining the gland. The primary reason for this is that it is extremely superficially situated, and as a result, high frequency probes may be utilised effectively to analyse such structures in great detail. In this work, an effort was made to investigate the function that USG plays in thyroid illnesses

Urine levels of rifampicin & isoniazid in asymptomatic HIV-positive individuals

Background & objectives: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. Methods: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV- positive individuals with CD4 cell counts > 350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. Results: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. Interpretation & conclusion: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies

Single dose pharmacokinetics of lamivudine in healthy volunteers: comparison of blood and urine kinetics

Aims: To study single dose pharmacokinetics of lamivudine (3TC) in healthy subjects. Methods: Twelve healthy subjects were administered 3TC (150 mg) followed by timed blood and urine collections up to 24 hours. Pharmacokinetic variables and percent dose of 3TC in urine were calculated. Results: Plasma exposure and percent dose of 3TC in urine were highly correlated (p < 0.001; r = 0.96). 3TC concentration at 24 hours was undetectable in all study subjects. Conclusions: Timed urine measurements could be used to study bioavailabilty of 3TC. Plasma 3TC measurements could be used to monitor adherence among HIV-infected patients on antiretroviral treatment.Aims: To study single dose pharmacokinetics of lamivudine (3TC) in healthy subjects. Methods: Twelve healthy subjects were administered 3TC (150 mg) followed by timed blood and urine collections up to 24 hours. Pharmacokinetic variables and percent dose of 3TC in urine were calculated. Results: Plasma exposure and percent dose of 3TC in urine were highly correlated (p < 0.001; r = 0.96). 3TC concentration at 24 hours was undetectable in all study subjects. Conclusions: Timed urine measurements could be used to study bioavailabilty of 3TC. Plasma 3TC measurements could be used to monitor adherence among HIV-infected patients on antiretroviral treatment

Sensitivity & specificity of combination testing algorithms for HIV in a tuberculosis clinic

Introduction: Co-management of tuberculosis (TB) and HIV is complicated by pharmacologic drug interactions between rifampicin (RMP) and certain classes of antiretroviral agents. The NNRTIs Nevirapine (NVP) or Efavirenz (EFV), used to HIV infection, are known to induce the CYP 450 enzyme system. Thus when RMP is co-administered along with NVP or EFV, the bioavailability of RMP could be lowered leading to drug resistance and treatment failure. Objectives: To study the steady state pharmacokinetics of RMP in HIV and HIV-TB patients receiving antiretroviral regimens containing NVP or EFV respectively. Methods: The study population comprised of HIV and HIV-TB patients undergoing antiretroviral treatment with NVP and EFV containing regimens respectively. These patients were also receiving concomitant RMP. Rifampicin was estimated by HPLC in blood collected at different time points after drug administration. The pharmacokinetic variables of RMP were calculated using WinNonlin software. Results & Conclusions: Co-administration of NVP or EFV did not alter the pharmacokinetics of RMP in HIV and HIV-TB patients, suggesting that the dose of RMP need not be altered during antiretroviral treatment with NVP or EFV

Acetylator status influences bioavailability of isoniazid in patients with advanced HIV disease

Patients with advanced HIV disease may exhibit malabsorption of anti-tuberculosis(TB) drugs. We evaluated the effect of isoniazid (INH) acetylator status on the bioavailability of INH in HIV-infected patients with and without tuberculosis, based on urinary excretion of the drug. Estimation of INH in urine collected up to 8 hours after oral administration of 300 mg INH were undertaken in 23 TB, 40 HIV and 26 HIV-TB patients. Determination of acetylator status of all these patients was also carried by differential estimations of INH and acetyl INH in urine collected between 5 and 6 hours after oral administration of 300 mg INH. Both slow and rapid acetylators in HIV and HIV-TB groups had significantly lower concentration of INH in urine compared to TB patients. The percent decrease in urinary excretion of INH was significantly higher in rapid than in slow acetylators, when compared to the corresponding TB patients. Acetylator status has an impact on the bioavailability of INH. Malbsorption in patients with advanced HIV disease may lead to decreased bioavailability of INH, particularly in rapid acetylators. Urinary estimation of INH provides reliable information on the bioavailability of the drug

WoW Post-CMOS compatible Cu-Cu Low temperature, Low pressure thermocompression bonding with Pd passivation Engineering

Surface passivation of Copper plays vital role in accomplishing low temperature, low pressure Wafer-on-Wafer (WoW) Cu-Cu thermocompression bonding, as it not only helps in protecting the Cu surface from oxidation but also smoothen the surface. Ultra-thin Palladium (Pd) layer is regarded as one of the promising passivation layer which can prevent oxidation of copper and in addition it can also minimize the roughness of Cu surface. The thickness of Pd layer plays an important role in achieving good and reliable bonding. In this endeavor, we have optimized the Pd passivation thickness to achieve low temperature (150 ˚C) and low pressure (4 bar) WoW Cu-Cu thermocompression bonding. The optimum thickness of Pd for achieving a good bonding is found out to be 3 nm. Our optimized result yielded an excellent bond interface confirms the reliability of Cu-Cu bonding with Pd passivation