The impact of Schiff bases on antibiotic production by Streptomyces hygroscopicus

A media consisting of isatin-Schiff bases (isatin-3-thiosemicarbazone, isatin-3-semicarbazone, and isatin-3-phenylhydrazone) was developed to maximize the production of antibiotics Hexaene H-85 and Azalomycine B by Streptomyces hygroscopicus. The media isatin-3-thiosemicarbazone resulted in the maximum antibiotics concentration of 372 μg cm⁻³ for Hexaene H-85 and 118 μg cm⁻³ for Azalomycine B. The impact of modified media on soil morphology also was investigated.     

Lack of effect of omeprazole or of an aluminium hydroxide/magnesium hydroxide antacid on the pharmacokinetics of lumiracoxib

OBJECTIVE: To evaluate the effects of multiple doses of omeprazole and of a single dose of an aluminium hydroxide/magnesium hydroxide (Al/Mg) antacid on the single-dose plasma pharmacokinetics of lumiracoxib. STUDY DESIGN: Open-label, randomised, three-period, crossover study. POPULATION STUDIED: Healthy subjects aged 18-65 years. METHODS: Fourteen subjects who met eligibility criteria were each administered three treatments in random order: (A) lumiracoxib 400 mg as a single oral dose; (B) oral omeprazole 20 mg once daily for 4 consecutive days, then lumiracoxib 400 mg as a single oral dose just prior to oral omeprazole 20 mg on day 5; and (C) lumiracoxib 400 mg as a single oral dose immediately prior to a 20 mL dose of Al/Mg antacid (magnesium hydroxide 800 mg and aluminium hydroxide 900 mg). The interval between each lumiracoxib dose was 7 days. Analysis of variance was performed to determine whether lumiracoxib alone differed from lumiracoxib plus omeprazole or from lumiracoxib plus Al/Mg antacid for overall exposure (area under the concentration-time curve from zero to infinity [AUC( infinity )]) and peak concentration (C(max)), with treatment sequence, subject, period and treatment as factors. Ratios of geometric means between lumiracoxib plus omeprazole and lumiracoxib plus Al/Mg antacid to lumiracoxib alone (reference) were calculated for AUC( infinity ) and C(max). If the mean ratios, with 90% CIs, fell within the interval 0.80-1.25, the treatments were considered equivalent. RESULTS: Arithmetic mean plasma lumiracoxib concentration-time profiles were similar for all treatments, with a rapid rise in concentration after administration, reaching C(max) values (mean +/- SD) of 9.24 +/- 1.96, 8.81 +/- 2.30, and 10.43 +/- 3.24 mg/L within 2-3 hours for treatments A, B and C, respectively. AUC( infinity ) was similar for the three treatments (36.75 +/- 7.73, 34.88 +/- 8.40 and 35.50 +/- 5.72 mg. h/L). All ratios of geometric means with 90% CIs fell within the interval used for establishing bioequivalence, except for the C(max) comparison between lumiracoxib plus Al/Mg antacid and lumiracoxib alone, which was 1.11 (0.95, 1.31). CONCLUSIONS: Coadministration of lumiracoxib with omeprazole or with an Al/Mg antacid had no clinically significant effect on lumiracoxib single-dose plasma pharmacokinetics. Lumiracoxib can, therefore, be administered concurrently with either of these agents without need for lumiracoxib dosage alteration.     

Assessment of Lumiracoxib Bioavailability from Targeted Sites in the Human Intestine Using Remotely Activated Capsules and Gamma Scintigraphy

PURPOSE: To determine the bioavailability and pharmacokinetic profile of lumiracoxib from different sites in the gastrointestinal tract. METHODS: Subjects (11 healthy adult males) were randomized to receive a 100 mg lumiracoxib dose, via a site-specific radiolabeled delivery capsule, to the stomach (internal reference), proximal small bowel, distal small bowel, or ascending colon. Gamma scintigraphy was used for real-time visualization of capsule location, and a radiofrequency signal was used to activate capsules at target site. RESULTS: Ten subjects completed the study. The mean capsule activation times for the stomach, proximal small bowel, distal small bowel, and ascending colon were 0.22, 1.52, 3.43, and 11.46 h post dose, respectively. Lumiracoxib was well absorbed from the proximal and distal small bowel, with AUC(0-infinity) ratios 104% (86, 127)% and 110% (89, 136)%, respectively. The highest Cmax (2413 ng/ml) and AUC(0-infinity) for lumiracoxib were in the distal small bowel (6842 ng x h/ml). Effective absorption was observed from the ascending colon, with an AUC(0-infinity) ratio of 85% (69, 104)% vs. the reference. CONCLUSIONS: Lumiracoxib is rapidly and efficiently absorbed throughout the gastrointestinal tract.     

Expression of the Bcl-2 family of proteins in peripheral blood B-lymphocytes in patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a neoplastic disease characterized by the accumulation of morphologically mature monoclonal CD 5+ B cells in the early phase (G0/G1) of the cell cycle. It is considered that the accumulation of neoplastically transformed lymphocytes B (CLL cells) is primarily the consequence of the disturbance, i.e., blockade of these cells' apoptosis process. Apoptosis is the specific process of programmed cell death regulated by numerous extracellular and intracellular mechanisms. The Bcl-2 proteins are well-known modulators of this process. Some of these proteins (such as Bcl-2, and Bcl-XI) are anti-apoptotic, while others (such as Bad or Bax) are pro-apoptotic. Our study included the analysis of 20 peripheral blood specimens from 20 patients with CLL, and 20 peripheral blood specimens of healthy persons who represented the control group. Using Western blotting analysis, we quantitatively examined the protein expression of Bcl-2 family (Bcl-2, Bax, Bad, and Bcl-XI). The level of Bcl-2 (p = 3.68 x 10(-10)), Bax (p = 0.019), and Bad (p = 0.073) proteins expression was significantly increased in all the analyzed peripheral blood samples of patients, while the level of Bcl-XI protein (p = 0.75) did not significantly differ in peripheral blood samples of patients, compared to the controls. The results of this study showed that the increased level of expression of Bcl-2, Bax, and Bad protein represented the most striking feature of CLL cells. Moreover, the variations in the expression of only one protein of the Bcl-2 family could not represent the prognostic parameter in the treatment of this disease.     

Psychostimulant treatment and risk for substance abuse among young adults with a history of attention-deficit/hyperactivity disorder: a population-based, birth cohort study

OBJECTIVE: The aim of this study was to evaluate the association between stimulant treatment and the risk for substance abuse among young adults with a childhood diagnosis of attention- deficit/hyperactivity disorder (ADHD). METHODS: Subjects included 295 research-identified ADHD incidence cases treated with psychostimulant medication and 84 ADHD cases not treated with psychostimulants. These subjects are from a 1976-1982 population-based birth cohort, retrospectively, followed from birth until emigration, death, or last follow-up (mean = 17.2 years of follow-up). Medical and school records were reviewed for documented substance abuse and psychostimulant treatment. The association was evaluated using logistic regression models. RESULTS: Socioeconomic characteristics at birth, and comorbidities, were similar between treated and untreated ADHD cases. Sixty (20.3%) of treated ADHD cases had documented substance abuse compared to 23 (27.4%) of cases not treated (OR = 0.7; 95% CI = 0.4-1.2). Among treated ADHD boys, 21.8% had substance abuse compared to 36.4% not-treated ADHD boys (OR = 0.5; 95% CI = 0.3-0.9). Among treated ADHD girls, 15.2% had substance abuse compared to 10.3% not-treated ADHD girls (OR = 1.5; 95% CI = 0.4-6.1). CONCLUSION: While these results cannot demonstrate cause and effect, our findings indicate that psychostimulant treatment of childhood ADHD is associated with reduced risk for later substance abuse among boys with ADHD.     

Immunoselection of functional CMRF-56+ blood dendritic cells from multiple myeloma patients for immunotherapy

Dendritic cells (DCs) loaded with tumor-associated antigens are a promising treatment to prevent disease relapse in patients with multiple myeloma (MM). Early-phase clinical trials have shown safety, efficacy, and immunologic responses in MM, but a key issue now is the isolation of a functional, clinically relevant DC preparation. The authors have described a unique blood DC (BDC) isolation platform based on positive immunoselection with the CMRF-56 antibody. To validate this as a feasible source of BDCs for immunotherapy, the authors undertook a quantitative and functional analysis of BDCs in MM patients and healthy donors. These data show that MM patients have similar numbers of CD11c+CD16+ and CD11c+CD16- BDCs but about half the number of CD11c-CD123+ BDCs in whole blood compared with healthy donors. BDCs could be isolated by CMRF-56+ immunoselection from all MM patients tested, with similar yields and purity to healthy donors. These BDCs could be activated ex vivo with poly I:C or LPS. Furthermore, CMRF-56+ preparations could induce potent CD4+ and CD8+ T-lymphocyte responses in both MM patients and healthy donors. These data suggest that BDCs with in vitro functional integrity can be isolated from MM patients in sufficient numbers to justify a clinical trial.     

Cigarette smoking in military pilots and intima-media thickness of the carotid arteries

BACKGROUND: It is well known that smoking is associated with an increase in arterial wall thickness. However, most studies of this problem have been undertaken in age and sex heterogenous groups, as well as in patients with already present other conventional risk factors. The aim of this study was to assess the effect of cigarette smoking on arterial wall thickness of the common carotid artery in asymptomatic pilots. METHODS: The imaging of intima-media thickness of the posterior wall of the distal 1 cm of both common carotid arteries was performed using a B mode ultrasound device, in 39 pilots (37.05 +/- 6.66 years), for whom smoking was the single cardiovascular risk factor. Comparisons were made with 49 non-smokers (35.12 +/- 7.39 years). RESULTS: The posterior walls of both common carotid arteries were thicker in smokers (left, p < 0.05; right, p > 0,05). Intima-media thickness was significantly lower on the right side than on the left side in both smokers and non-smokers (p < 0.01). CONCLUSION: Cigarette smoking as the single cardiovascular risk factor was associated with the wall thickness of the carotid arteries in our study. This finding indicated that early atherosclerosis was already present in pilots-smokers entering middle age.     

Exposure and allergy to dust mites in general and working environment in Croatia

This paper gives a review of the most important impacts of exposure to dust mites in general and working environment on human health. The Institute for Medical Research and Occupational Health in Zagreb, Croatia, has been investigating the frequency and exposure levels of allergies to pyroglyphid and non-pyroglyphid mites in Croatia for the last 10 years. Investigations were performed in general urban and rural population from the inland and coastal Croatia, and several industrial inland populations occupationally exposed to organic dusts. Mite species and levels of pyroglyphid mites allergens (Der p 1, Der f 1) were established in house dust samples taken from the floors of bedrooms and living rooms and in several industrial dust samples. The frequency of allergies to pyroglyphid mites in general urban population of inland Croatia is about 20%, with significant general indoor exposure to these mites (median value for Der p 1: 0.85 microg/g of dust). General adult population of the coastal region had a significantly higher exposure to pyroglyphid mites (median value for Der p 1: 4.5 microg/g of dust), yet showed a significantly lower frequency of allergies to these mites (about 5%). New studies are necessary to investigate possible genetic and environmental factors involved in the mechanisms which protect coastal population from the development of mite allergy. Acarological and statistical analyses have shown that the high frequency of sensitisation to non-pyroglyphid mites found in the general and working populations of the inland region is not related to environmental exposure to these mites, but to the cross-reactivity between pyroglyphid and non-pyroglyphid mites and to false positive skin reactions in prick testing, particularly to T. putrescentiae. So far, results do not indicate that pyroglyphid mites are occupational allergens in paper-recycling, fish-processing and tobacco-processing.     

Protection against cutaneous leishmaniasis in outbred vervet monkeys using a recombinant histone H1 antigen

Infection with Leishmania major parasites results in the development of cutaneous ulcerative lesions on the skin. We investigated the protective potential of a single, recombinant histone H1 antigen against cutaneous leishmaniasis in an outbred population of vervet monkeys, using Montanide adjuvant. Protection was assessed by challenging the animals with a mixture of vector sand fly salivary-gland lysate and a low dose of in vitro-derived parasites, thus more closely mimicking natural infection induced by L. major. The course of infection in immunized monkeys was compared with that of animals that had healed from a primary infection and were immune. The monkeys immunized with recombinant histone H1 showed a reduced development of lesion size, compared with controls. Our study therefore illustrates the potential use of histone H1 as a vaccine candidate against cutaneous leishmaniasis in humans.     

Structure and homogeneity of pseudo-physiological phospholipid bilayers and their deposition characteristics on carboxylic acid terminated self-assembled monolayers

Supported phospholipid bilayers are frequently used to establish a pseudo-physiological environment required for the study of protein function or the design of enzyme-based biosensors and biocatalytic reactors. These membranes are deposited from bilayer vesicles (liposomes) that rupture and fuse into a planar membrane upon adhesion to a surface. However, the morphology and homogeneity of the resulting layer is affected by the characteristics of the precursor liposome suspension and the substrate. Here we show that two distinct liposome populations contribute to membrane formation – equilibrium liposomes and small unilamellar vesicles. Liposome deposition onto carboxylic acid terminated self-assembled monolayers resulted in planar mono- and multilayer, vesicular and composite membranes, as a function of liposome size and composition. Quartz crystal microbalance data provided estimates for layer thicknesses and sheer moduli and were used for classification of the final structure. Finally, atomic force microscopy data illustrated the inherently inhomogeneous and dynamic nature of these membranes.