Determination of lercanidipine in human plasma by an improved UPLC-MS/MS method for a bioequivalence study$ / 药物分析学报

An improved and reliable ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS) method has been developed and validated for the determination of lercanidipine in human plasma. Plasma samples with lercanidipine-d3 as an internal standard (IS) were prepared by solid phase extraction on Phenomenex Strata-X cartridges using 100 mL of human plasma. Chromatographic analysis was performed on UPLC BEH C18 (50 mm ? 2.1 mm, 1.7 mm) column under isocratic conditions. Linear calibration curves were obtained over a wide dynamic concentration range of 0.010–20.0 ng/mL. Matrix effect was assessed by post-column infusion, post-extraction spiking and standard-line slope methods. The mean extraction recovery was 4 94%for the analyte and IS. Inter-batch and intra-batch precision (%CV) across five quality controls was o 5.8%. Bioequivalence study was performed with 36 healthy sub-jects after oral administration of 10 mg of lercanidipine and the assay reproducibility was evaluated by reanalysis of 133 incurred samples.

Current scenario of Opportunistic and co-infections in HIV-infected individuals at a tertiary care hospital in Mumbai, India.

Purpose: An update on opportunistic infections/co-infections (OIs/CIs) is essential to understand the success of highly active antiretroviral therapy offered by the government agencies in reducing AIDS-related OIs/CIs. Hence, the present study aimed to evaluate the frequency of OIs/CIs in HIV-positive individuals at a tertiary care hospital in Mumbai. Its’ association with CD4 counts, anti-retroviral treatment and on HIV transmission was also determined. Materials and Methods: An observational study was designed to evaluate different OIs/CIs in individuals, who tested positive for HIV infection at the ICTC/Shakti Clinic of Seth G.S. Medical College and KEM Hospital, Mumbai. Data analysis was done with the use of SPSS software (version 19.0, SPSS, Chicago, IL, USA). P value was considered signifi cant if it is < 0.05. Results: Heterosexual contact was the major route of transmission among the enrolled 185 individuals. Ninety (48.06%) HIV-infected individuals were with OIs/CIs. Tuberculosis (TB) was the most common OI (68.8%). Other CIs noted were Herpes zoster, syphilis, hepatitis C and B, malaria, typhoid and dengue. The median CD4 count in HIV-positive individuals with TB was 337 ± 248 cells/μl, and 67.7% of individuals with OIs/CIs had low CD4 counts (<400 cells/μl). Individuals in 31-40 years of age group had signifi cantly (P = 0.01) more OIs/CIs. More (53.7%) spouse/children of HIV-positive individuals without OIs/CIs were HIV-1 positive. Low proportions of individuals with or without OIs/CIs were on ART. Conclusion: Nearly half of HIV-infected individuals were with OIs/ CIs. Initiation of free ART programme since 2004 possibly associated with the type and rate of OIs/CIs. Tuberculosis and multiple OIs/CIs were associated with low CD4 counts. Infection was high in 31-40 years age group. Most of the spouses of individuals without OIs/CIs were HIV positive, indirectly indicates lack of condom use or lack of awareness of condom use.

Referral pattern for neoadjuvant chemotherapy in the head and neck cancers in a tertiary care center.

BACKGROUND: Use of any treatment modality in cancer depends not only on the effectiveness of the modality, but also on other factors such as local expertise, tolerance of the modality, cost and prevalence of the disease. Oropharyngeal and laryngeal cancer are the major subsites in which majority of neoadjuvant chemotherapy (NACT) literature in the head and neck cancers is available. However, oral cancers form a major subsite in India. MATERIALS AND METHODS: This is an analysis of a prospectively maintained data on NACT in the head and neck cancers from 2008 to 2012. All these patients were referred for NACT for various indications from a multidisciplinary clinic. Descriptive analysis of indications for NACT in this data base is presented. RESULTS: A total of 862 patients received NACT within the stipulated time period. The sites where oral cavity 721 patients (83.6%), maxilla 41 patients (4.8%), larynx 33 patients (3.8%), laryngopharynx 8 patients (0.9%) and hypopharynx 59 patients (8.2%). Out of oral cancers, the major indication for NACT was to make the cancer resectable in all (100%) patients. The indication in carcinoma of maxilla was to make the disease resectable in 29 patients (70.7% of maxillary cancers) and in 12 patients (29.3% of maxillary cancers) it was given as an attempt to preserve the eyeball. The indication for NACT in laryngeal cancers was organ preservation in 14 patients (42.4% of larnyngeal cancer) and to achieve resectability in 19 patients (57.6% of larnyngeal cancer). The group with laryngopharynx is a cohort of eight patients in whom NACT was given to prevent tracheostomy, these patients had presented with early stridor (common terminology criteria for adverse events Version 4.02). The reason for NACT in hypopharyngeal cancers was for organ preservation in 24 patients (40.7% of hypopharyngeal cancer) and for achievement of resectability in 35 patients (59.3% of hypopharyngeal cancer). CONCLUSION: The major indication for NACT is to make disease resectable at our center while cases for organ preservation are few.

Wound Healing Activity of Premna latifolia Roxb.

Aims: The study aims to understand the wound healing potentials of a 50% aqueous ethanolic extract of Premna latifolia stem using excision wound model. Study Design: The wound healing potentials were simultaneously supported by observing the bacterial functional diversity of wound swabs using Biolog Eco plates. The antioxidant activity was performed using In vitro DPPH free radical scavenging assay. Place and Duration of Study: CSIR-National Botanical Research Institute (NBRI), Lucknow, between May 2013 and November 2013. Methodology: Wound healing activity of the plant was studied using excision wound model. Animals were divided into three groups of six male rats each as control group (GI) dressed with compound free simple ointment. Test group (GII) treated with 50% aqueous ethanolic extract of P. latifolia stem (10% w/w) in ointment vehicle and standard group (GIII) group treated Nitrofurazone ointment, Himedia (0.2%w/w). The wound healing potential was further supported by the DPPH free radical scavenging and antibacterial activity of the plant. The phytochemical estimations were done using standard methods. Results: Sugar and starch content in the plant was 3.55% and 5.54% respectively. Total tannins, phenol and flavonoid content were estimated to be 0.18%, 0.54% and 2.73%. The 50% ethanolic extract of the plant showed moderate DPPH free radical scavenging activity with an IC50 of 188.02μg/ml. A 69.15% of wound closure was observed on 10th day post wounding of the rats treated with 200 mg/kg of extract. The results also indicated significant antibacterial activity of the extract. Conclusion: The 50% aqueous ethanolic extract of P. latifolia shows significant wound healing activity.

In vitro microtuberization in potato (Solanum tuberosum L.) cultivars.

Mechanism of microtuberization in three elite cultivars kufri badhsha (KB), kufri chandramukhi (KCM) and kufri jawahar (KJ) of potato was studied. Sprouts of all the three cultivars were used to obtain in vitro shoot cultures. MS medium supplemented with chlorocholine chloride was found to be most suitable for all the cultivars. Maximum tuberization was obtained under incubation conditions of continuous darkness at 20 degrees +/- 1 degrees C. The highest number of micro-tubers per plant basis was produced under continuous darkness and KCM recorded the highest yield of micro-tubers and was found significantly superior to KJ and KB.

Significance of haematological manifestations in patients with tuberculosis.

OBJECTIVE: Tuberculosis is a major public health problem in India. Haematological changes associated with tuberculosis have been incompletely investigated. To the best of our knowledge, there is no comprehensive study assessing the haematological abnormalities in these patients from the Indian subcontinent. In the present study, we have compared peripheral blood and bone marrow findings in patients with disseminated/miliary tuberculosis (DTB/MTB) as well as pulmonary tuberculosis (PTB). An attempt has also been made to assess the effect of antituberculosis therapy on the haematologic abnormalities. MATERIAL AND METHODS: Thirty two patients with disseminated/miliary tuberculosis and 23 patients with pulmonary tuberculosis were prospectively studied to determine the various haematological manifestations in tuberculosis and the effect of antituberculosis therapy. All patients received standard antituberculosis treatment. They were subjected to a detailed haemogram including peripheral blood examination, which was repeated on completion of antituberculosis therapy. Bone marrow aspiration and biopsy was also done in all patients before starting antituberculosis treatment. RESULTS: Normocytic normochromic anaemia was the most common abnormality observed in all the groups and subgroups (DTB/MTB 84%, PTB 86%). Other haematological abnormalities of the white blood cells include leucopenia (DTB/MTB 25%, PTB 0%; p < 0.02), neutropenia (DTB/MTB 22%, PTB 0%; p < 0.04), lymphocytopenia, monocytopenia, leukocytosis, neutrophilia, lymphocytosis and monocytosis. Pancytopenia was observed only in patients with disseminated/miliary tuberculosis (p < 0.05). Thrombocytopenia was more common in patients with disseminated/miliary tuberculosis (p < 0.007), whereas thrombocytosis was more common in patients with pulmonary tuberculosis (p < 0.04). The patients of disseminated/miliary tuberculosis with granulomas in the bone marrow had certain significant differences as compared to patients without granulomas. These patients showed severe anaemia, peripheral monocytopenia and bone marrow histiomonocytosis. The haemogram reverted to normal with antituberculosis therapy in these patients. CONCLUSIONS: In view of the varied haematological abnormalities observed in patients with tuberculosis in this part of the world, it is concluded that the differential diagnosis of tuberculosis should be entertained in patients with varied haematological disorders.

Construction and characterization of M13 bacteriophages displaying gp120 binding domains of human CD4.

The envelope glycoprotein, gp120, on the surface of HIV interacts with the human CD4 molecule and thus helps the virus in gaining entry into the T-helper cells. To display the gp120 binding domains of human CD4 on the surface of the bacteriophage M13, two types of vectors have been constructed. In these, the first 176 amino acids of the human CD4 have been fused with the minor coat protein, gIIIp, of M13 bacteriophage for surface display. The Western blot analysis revealed that using the phage based vector, M13CD41923, all the copies of gIIIP (3-5 per virion) were present as fusion protein indicating multivalent display. In the phagemid based vector, phage particles were produced only upon infection of the cells carrying pVCCD43426, with the helper phage, M13KO7. Thus these phage particles carried both, the fusion protein as well as the unfused gIIIp, as shown by Western blot analysis. The presence of large amount of unfused gIIIp ensured that the phage particles did not display more than one fusion protein per phage particle, thus leading to monovalent display. Phage particles produced by both vectors could be captured on immobilized gp120, thereby showing that the displayed CD4 domains were functional.

Alcohol consumption and hypertension.

The effect of acute alcohol consumption was studied in healthy subjects (Group-I) and in nondrinking hypertensive (Group-II) and in regularly drinking hypertensive patients (Group-III). All subjects consumed alcohol (1gm/kg body weight daily) for 5 days, then abstained for 5 days. Blood pressure was recorded in standing and supine position every morning. Group-I showed no significant difference in blood pressures during and after alcohol consumption. Group-II showed a statistically significant increase in the supine and standing systolic/diastolic and mean blood pressure when consuming alcohol (P < 0.01) as compared to the period of abstinence. In Group-III, hypertensive patients who drank regularly showed significant decrease in systolic blood pressure in the period of abstinence during standing (p < 0.02) as well as in supine position (p < 0.001) and diastolic and mean blood pressure reduction in standing and supine position (p < 0.01) as compared to the period of drinking.

Rheumatic heart disease: a school survey in a rural area of Rajasthan.

Thirty four of 10168 school going children were found to have rheumatic heart disease (RHD) in a school survey conducted in the rural areas of Churu district in Rajasthan. The prevalence rate was 3.34/1000. A high prevalence of RHD was found in 11 to 15 year age group. Maximum prevalence of RHD was in low socioeconomic group. Out of these thirty four cases of RHD, isolated mitral stenosis was present in sixteen, isolated mitral regurgitation in four, combined mitral stenosis and mitral regurgitation in ten patients.

Epidemiological study of hypertension in a rural community of western Rajasthan.

The prevalence of hypertension was studied in a rural community of western Rajasthan comprising of 6840 subjects in the age range of 21-70 years. The overall prevalence of hypertension was 3.8 percent. It was 4.0 percent in males and 3.6 percent in females. The prevalence of hypertension increased with age in a linear fashion.

Tetanus in leprosy patient (II).

Leprosy patients are protected from tetanus due to acquired natural immunity against tetanus. The incidence of tetanus in Leprosy is very low. A case of Indeterminate Leprosy developing tetanus following injury and terminating fatally is presented.