Interaction of Ketotifen Fumarate with Anhydrous Theophylline in Simulated Gastric and Intestinal Media and Effect on Protein Binding

Purpose: The purpose of the present study was to investigate interaction between ketotifen fumarate and anhydrous theophylline in aqueous media of various pH.Methods: By using Job’s continuous-variation analysis and Ardon’s spectrophotomeric methods, the values of stability constants of theophylline with ketotifen were determined at a fixed temperature (37 0C) at each of the medium pH. In vitro study of protein (bovine albumin, fraction v) binding was carried out by equilibrium dialysis method at pH 7.4 to ascertain the influence of ketotifen on the protein binding of theophylline.Results: Stability constant, ranging between 5.07 and 6.35, were derived from Ardon’s plot, indicating that complexes formed, as a result of interaction between the drugs, were comparatively stable. However, following theophylline interaction with ketotifen, stability constant was < 1 at gastric pH (0.4 and 2.0) and 4.12 at intestinal pH. (6.0)The highest degree of protein binding by ketotifen was 98 % and the lowest 90 %. For theophylline, the highest and lowest degrees of protein binding were 90 and 85 %, respectively.Conclusion: Concurrent administration of ketotifen and theophylline would result in the formation of a stable complex and this is likely to reduce the therapeutic activities of both drugs. With regard to protein binding, the concentration of theophylline increased with decrease in ketotifen concentration.Keywords: Stability constant, Job’s method, Ardon’s method, Ketotifen fumarate, Complex formation, Protein binding, Theophyllin

Management of TB in the private sector in Khartoum, Sudan: quality and impact on TB control

IntroductionSudan has a large and growing private health sector. No survey was done in Sudan to show the extent of the use of private health care services by the population. Also precise data on tuberculosis (TB) diagnosis and treatment in the private sector are not available.Material and methodsA facility-based cross-sectional survey was carried out during February2007-June 2007 in Khartoum state, whereby consented private physicians working in the all private clinics (n=110) were interviewed.ResultsThis study showed that a large private sector exist in the country and deliver care to TB patients and reported the non-adherence of this sector to National Tuberculosis Program (NTP) guidelines. 59.1% of the interviewed physicians correctly mentioned the TB treatment regimens, only 8(12.3%) physicians that reported management of TB patients actually prescribed these regimens to their patients. Similarly, only 10(15.4%) physicians requested sputum smear examination for TBdiagnosis.ConclusionA considerable proportion of cases is inadequately managed by the private sector and is not notified to NTP. The information delivered by this study can be used to develop a workable Public-private mix (PPM) model with the private sector.Key words: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol

Screening vaccine formulations for biological activity using fresh human whole blood.

Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression

Efficient production of transgenic soybean (Glycine max [L] Merrill) plants mediated via whisker-supersonic (WSS) method

The present study was designed to evaluate the transformation efficiency and proof the capability of whisker supersonic (WSS) method as an alternative option for soybean (Glycine max [L] Merrill)transformation. We compared soybean transformation efficiency obtained by WSS-mediated with that of particle bombardment transformation by carrying out molecular analysis of the T0 plants in two independent experiments. For this, we used for both transformation techniques the same genotype, the same plasmid and the same selection method. To assess the efficiency of soybean genetictransformation, we evaluated the efficiency of multi gene transformation by the selection with hygromycin and the expression of green fluorescent protein [sGFP (S65T)] resulted from both techniques. Regenerable embryogenic cells were induced from immature cotyledons of soybean c.v Jack on MSD40 media within 3 weeks then proliferated on FN lite liquid media and engineered with pUHG gene construct through both WSS and particle bombardment-mediated transformation. The pUHG was constructed with pUC 19 and contain the hpt gene conferring resistance to hygromycin as a selective marker and sGFP(S65T) as a reporter gene. Fluorescence microscopy screening after the selection of hygromycin, identified the clearly expression of sGFP(S65T) in the transformed soybean embryos. Stable integration of the transgenes was confirmed by polymerase chain reaction (PCR) andSouthern blot analysis. The average transformation efficiency achieved with WSS was higher than that obtained by particle bombardment and hence it may represent an alternative method for soybeantransformation

Long-run relationship between sectoral productivity and energy consumption in Malaysia: An aggregated and disaggregated viewpoint

This paper investigates the causal relationship between energy consumption and economic productivity in Malaysia at both aggregated and disaggregated levels. The investigation utilises total and sectoral (industrial and manufacturing) productivity growth during the 1971–2012 period using the modified Granger causality test proposed by Toda and Yamamoto [1] within a multivariate framework. The economy of Malaysia was found to be energy dependent at aggregated and disaggregated levels of national and sectoral economic growth. However, at disaggregate level, inefficient energy use is particularly identified with electricity and coal consumption patterns and their Granger caused negative effects upon Gross Domestic Product (GDP) and manufacturing growth. These findings suggest that policies should focus more on improving energy efficiency and energy saving. Furthermore, since emissions are found to have a close relationship to economic output at national and sectoral levels green technologies are of a highest necessity

Selection of an efficient in vitro micropropagation and regeneration system for potato (Solanum tuberosum L.) cultivar Desirée

Sprouts of about 40 to 80 mm length were excised, surface sterilized with 70% CloroxR and cultured on solid full-strength Murashige and Skoog (MS) medium. Shoot nodal segments (1.0 cm) from in vitro plantlets (2 to 4 weeks old) were multiplied through periodic subculturing on full-strength MS medium with 30 g/L sucrose, 100 ml/L myo-inositol and 0.5 ml/L silver thiosulfate. The shoots were rooted on the same medium. Microtubers were stimulated on MS medium supplemented with 80 g/L sucrose, 100 ml/L myo-inositol and 5 ml/L benzyl adenine. They generally originate on aerial etiolated shoots producing . 1.0 } 0.5 microtuber/explant with diameter approx. 3 to 10 mm. Shoot regeneration was performed from  tuber discs, internodes and leaf explants using 6 different media. Different regeneration capacities were  observed by the explants along 60 days. The average number of shoots was highest from tuber discs (6.2)  than from leaf explants (2.6) which exceeds about three times; no shoot from internode explants cultured on the various media. Regenerated plantlets produced from both tuber discs and leaf explants exhibited random amplification of polymorphic DNA (RAPD) analysis using five selected primers to detect  somaclonal variation. All the morphological variants were excluded. One of the regenerated plantlet  derived from leaf-explants was true-to-type to the main in vitro plantlet, so it will be used as a source of explants for transformation experiments. The other regenerated plantlets derived from leaf explants and tuber discs show the presence and/or absence of polymorphic bands. Results also showed that  microtubers were initiated on the etiolated shoots of the regenerants at the first 10 days. The etiolated shoots induced about 2.6 } 0.6 and 2.2 } 0.5 microtuber/explants.Key words: Solanum tuberosum L., seed tuber, sprouting, micropropagation, microtubers, explants, regeneration, random amplification of polymorphic DNA (RAPD)

Translation, cultural adaptation and field-testing of the Thinking Healthy Program for Vietnam

Background: Depression and anxiety are prevalent among women in low- and lower-middle income countries who are pregnant or have recently given birth. There is promising evidence that culturally-adapted, evidence-informed, perinatal psycho-educational programs implemented in local communities are effective in reducing mental health problems. The Thinking Healthy Program (THP) has proved effective in Pakistan. The aims were to adapt the THP for rural Vietnam; establish the program’s comprehensibility, acceptability and salience for universal use, and investigate whether administration to small groups of women might be of equivalent effectiveness to administration in home visits to individual women. Methods: The THP Handbook and Calendar were made available in English by the program developers and translated into Vietnamese. Cultural adaptation and field-testing were undertaken using WHO guidance. Field-testing of the four sessions of THP Module One was undertaken in weekly sessions with a small group in a rural commune and evaluated using baseline, process and endline surveys. Results: The adapted Vietnamese version of the Thinking Healthy Program (THP-V) was found to be understandable, meaningful and relevant to pregnant women, and commune health centre and Women’s Union representatives in a rural district. It was delivered effectively by trained local facilitators. Role-play, brainstorming and small-group discussions to find shared solutions to common problems were appraised as helpful learning opportunities. Conclusions: The THP-V is safe and comprehensible, acceptable and salient to pregnant women without mental health problems in rural Vietnam. Delivery in facilitated small groups provided valued opportunities for role-play rehearsal and shared problem solving. Local observers found the content and approach highly relevant to local needs and endorsed the approach as a mental health promotion strategy with potential for integration into local universal maternal and child health services. These preliminary data indicate that the impact of the THP-V should be tested in its complete form in a large scale trial

Predictors of spontaneous remission and recovery among women with untreated perinatal depression in India and Pakistan

Abstract Background Mothers with perinatal depression can show different symptom trajectories and may spontaneously remit from depression, however, the latter is poorly understood. This is the first study which sought to investigate predictors of spontaneous remission and longer-term recovery among untreated women with perinatal depression. Methods We analysed data from two randomised controlled trials in women with perinatal depression in India and Pakistan. Analyses were restricted to women in the control groups who did not receive active treatment. Generalised estimating equations and logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for within-person correlation. Results In multivariable analyses, remission was associated with a husband who is not working (adjusted OR, aOR = 2.04, 95% CI 1.02–4.11), lower Patient Health Questionnaire-9 score at baseline (aOR = 0.43, 95% CI 0.20–0.90 for score of ≥20 vs. 10–14) and better social support at baseline (aOR = 2.37, 95% CI 1.32–4.27 for high vs. low social support). Conclusions Women with low baseline severity may remit from perinatal depression with adequate social support from family and friends. These factors are important contributors to the management of perinatal depression and the prevention of clinical worsening, and should be considered when designing low-threshold psychological interventions. </jats:sec