In vitro antibacterial activity of the volatile oil of Nigella sativa seeds against multiple drug-resistant isolates of Shigella spp. and isolates of Vibrio cholerae and Escherichia coli

The antibacterial activity of the volatile oil of Nigella sativa seeds was studied against 37 isolates of Shigella dysenteriae 1, Shigella flexneri, Shigella sonnei and Shigella boydii and 10 strains of Vibrio cholerae and Escherichia coli. Most of the strains were clinically resistant to ampicillin, co-trimoxazole and tetracycline. All the strains tested showed promising sensitivity to the volatile oil. The minimum inhibitory concentration (MIC) of the volatile oil for Shigella, Vibrio and Escherichia strains tested was between 50–400 μg/mL.     

CD8 expression on B cells in chronic lymphocytic leukemia: a case report and review of the literature

The expression of CD8, a restricted T-cell antigen, on B cells in B chronic lymphocytic leukemia is rare, and its significance, if any, remains unknown. We report herein a patient with B chronic lymphocytic leukemia in whom CD8 was strongly expressed on all B cells, both in the bone marrow and peripheral blood. The patient required no therapy for 6 years after being diagnosed as having B chronic lymphocytic leukemia. Then, when the disease progressed, he was treated with conventional doses of fludarabine phosphate (25 mg/m(2) daily for 5 days), but unlike other patients with B chronic lymphocytic leukemia he tolerated this therapy poorly. He received a total of only 4 series of fludarabine therapy, and following each course of treatment, he developed considerable myelosuppression. After the fourth course of therapy, his bone marrow failed to show any evidence of regeneration, and he died as a result of intercurrent respiratory tract infection 1 month after his last dose of fludarabine was given.     

CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

Background  

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.     

Performance characteristics of a microMOSFET as an in vivo dosimeter in radiation therapy

The commercially available microMOSFET dosimeter was characterized for its dosimetric properties in radiotherapy treatments. The MOSFET exhibited excellent correlation with the dose and was linear in the range of 5-500 cGy. No measurable effect in response was observed in the temperature range of 20-40 degrees C. No significant change in response was observed by changing the dose rate between 100 and 600 monitor units (MU) min(-1) or change in the dose per pulse. A 3% post-irradiation fading was observed within the first 5 h of exposure and thereafter it remained stable up to 60 h. A uniform energy response was observed in the therapy range between 4 MV and 18 MV. However, below 0.6 MeV (Cs-132), the MOSFET response increased with the decrease in energy. The MOSFET also had a uniform dose response in 6-20 MeV electron beams. The directional dependence of MOSFET was within +/-2% for all the energies studied. The inherent build-up of the MOSFET was evaluated dosimetrically and found to have varying water equivalent thickness, depending on the energy and the side of the beam entry. At depth, a single calibration factor obtained by averaging the MOSFET response over different field sizes, energies, orientation and depths reproduced the ion chamber measured dose to within 5%. The stereotactic and the penumbral measurements demonstrated that the MOSFET could be used in a high gradient field such as IMRT. The study showed that the microMOSFET dosimeter could be used as an in vivo dosimeter to verify the dose delivery to the patient to within +/-5%.     

Evaluation of the 2016–2020 regional tuberculosis response framework,WHO Western Pacific Region

ObjectiveTo assess the implementation of the Regional framework for action on implementation of the End TB Strategy in the Western Pacific, 2016–2020 in countries and areas in the World Health Organization Western Pacific Region.MethodsWe used a mixed methods approach to assess the framework’s measurable and perceived impact. We conducted an analysis of national tuberculosis strategic plans, a cross-sectional survey of senior staff of tuberculosis programmes, key informant interviews and some country case studies.FindingsOf the 37 countries and areas of the Western Pacific Region, 14 had a national tuberculosis strategic plan, including all countries and areas with a high incidence of tuberculosis. Most senior tuberculosis programme staff who responded to the survey (16/23) found the regional framework useful when developing their national targets and grant applications. Programmatic challenges identified included financing, human resources, public–private mix, active case finding, and paediatric and drug-resistant tuberculosis. Most of the 17 key informants thought that the regional framework’s categorization of actions (for all settings, for specific settings and for pre-elimination settings) was useful, but that the added value of the regional framework over other relevant documents was not obvious because of overlap in content.ConclusionThe regional framework influenced national level tuberculosis control planning and implementation in a positive way. A future regional framework should provide a longer-term strategic horizon and specifically address emerging trends and persistent problems faced by countries or areas of the region.     

Uptake of chloroform by skin on brief exposures to the neat liquid

The uptake of chloroform into hairless rat's stratum corneum after application of the neat solvent directly to the skin has been studied. Tape stripping was used to determine amounts deposited within the stratum corneum and also the clearance of the compound from the skin following varied levels of exposure. Three minutes exposure to neat chloroform was adequate to achieve a limiting accumulation in the stratum corneum and thus it appears to take this long for the gradient of chloroform to be established fully across this structure. There was indication of progressively deeper penetration of chloroform as the exposure time was increased from 1 to 8 minutes. Local irritation and a loosening of the superficial layers of stratum corneum were apparent with as little as 2 minutes of exposure to the solvent and were exacerbated with further increases in exposure duration. Following exposure, clearance of the solvent from the skin surface was rapid. Interestingly, the rate of clearance, as followed by stripping, was comparable on live and freshly euthanized rats. This implies that once the exposure is terminated evaporation from the surface, and not systemic uptake by way of the local vasculature, is the predominant means of clearance at an open surface.     

Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.