Bioavailability studies on guar gum-based three-layer matrix tablets of trimetazidine dihydrochloride in human volunteers.

Guar gum-based three-layer matrix tablets of a highly water-soluble drug, trimetazidine dihydrochloride, were evaluated for their in vivo release in healthy volunteers in comparison with commercially available conventional immediate release tablets. Six healthy volunteers participated in the study and a two-way crossover design was followed. The plasma concentration of trimetazidine dihydrochloride was estimated by reverse-phase HPLC. The pharmacokinetic parameters were calculated from the plasma concentration of trimetazidine dihydrochloride versus time data. The delayed T(max), decreased C(max) and K(a), unaltered bioavailability, and prolonged t(1/2) and MRT indicated a slow and prolonged release of trimetazidine dihydrochloride from guar gum three-layer matrix tablets in comparison with the immediate release tablet dosage form. The guar gum three-layer matrix tablets of trimetazidine dihydrochloride may be useful in providing constant drug delivery with minimum fluctuations.     

Nitroblue-tetrazolium test for the functional evaluation of phagocytic cells: A critical analysis of the methodology

The reduction of NBT to formazan has been suggested as an indicator of the reduction potential of biological systems. An increase in the amount of reduced formazan reflects the activation of the hexose monophosphate shunt of phagocytes cultivated in vitro, as a result of cellular stimulation by chemical or biological factors, or during phagocytosis. This phenomenon has been widely used for the determination of activated phagocytes by different methods. However, the technical limitations of these methods have not been evaluated carefully. In the investigations presented here threesolvents for formazan, pyridine, dioxane and dimethylformamide, have been tested for their suitability as extraction agents. For each solvent the optimal wavelength for photometric evaluation has been determined and dose relation curves between dissolved formazan and OD have been established. Several factors (time, temperature, pH, contamination with water or acid) affecting the dissolving properties and stability of formazan in different solvents have been investigated. With the solvents tested, dioxane proved to be the most suitable agent for extracting NBF. Thus, a methodology for the quantitative evaluation of NBT has been established. This method can be used for the identification of activators as well as of inhibitors of the phagocyte system.     

Type A behavior and psychological characteristics of hypertensive patients undergoing antihypertensive treatment

The aim of this study was to evaluate the presence of "type A" behaviour and possible psychological distress in 373 hypertensive patients. One-hundred and ninety-five males, 56.2 +/- 6.2 years old and one-hundred and seventy-eight females, 57.1 +/- 6.2 years old, coming from the IPPPSH and still under double-blind treatment with or without a beta-blocker (oxprenolol 160 mg SR), were studied by means of the Jenkins Activity Survey form C and several tests from the Cognitive Behavioural Assessment Battery (CBA-2.0). Seventy-four point eight percent of the patients showed a "type A" pattern, and 25.5% were in the extreme predictive interval for coronary heart disease according to WCGS. "Type A" pattern was not influenced by variables such as age, sex, education, job or previous pharmacological treatment. The patients studied did not show any particular psychological distress at the psychometric evaluation. However, special social and cultural characteristics and different therapies influenced some symptoms, such as anxiety, depression and somatic lamentation. According to this study: "type A" behaviour seems to be a steady feature of the hypertensive patient; furthermore, it seems to be due to a "biological imprinting" which can be considered a cause of hypertension; psychological distress depends on a particular set of environmental stimuli. In the first case an accurate prevention is needed while, in the second case adequate pharmacological and/or psychological therapies are needed.     

RNA tumor virus phosphoproteins: subvirion location of the multiple phosphorylated species.

An analysis of core particles of 1.23 g/cm³ density of the endogenous feline type C virus (RD-114) showed the presence of all of the major low molecular weight structural proteins, namely p30, p12, p10, and the phosphoprotein pp15, in relative proportions similar to those detected in intact RD-114 virions. The protein kinase activity of the virus was also found to be associated with the core. A comparison of the content of multiple phosphorylated species of the pp15 derived from the core with that isolated from the whole virion demonstrated that all major phosphorylated species of RD-114 pp15 were located in the core structure.     

Spectrum of dolichospondylic dysplasia: two new patients with distinctive findings

Dolichospondylic dysplasia (DD) is a rare skeletal dysplasia primarily characterized by tall vertebral bodies and disproportionate short stature. Radiographic manifestations include tall vertebral bodies and gracile bones of the hands. Patients usually have eye and ear findings in addition to borderline mental retardation; however, tall vertebral bodies and slender tubular bones are also seen in the 3-M syndrome. Patients with the 3-M syndrome have a characteristic face with a triangular shape, frontal bossing, a flattened malar region, full eyebrows, a short nose with a bulbous tip, upturned nares, and full lips. We present two unrelated patients who share a distinct phenotype and have tall vertebral bodies, overtubulation of long bones, and short tubular bones of the hands and feet. We discuss the overlapping and distinguishing features between DD and the 3-M syndrome. Patient 1 was a 13-year-old female, and patient 2 was an unrelated adult female. These patients had normocephaly and short stature. They shared a common phenotype consisting of mild malar hypoplasia, a narrowed nasal body with a fleshy tip, full lips, and normal intelligence. In addition, they showed mild hand and foot abnormalities. These two patients lack many of the typical clinical features of both DD and the 3-M syndrome. They share a common phenotype and likely represent a distinct disorder. The spectrum of disorders with tall vertebral bodies as a key feature may include different entities that may be further defined with the characterization of the molecular defect(s).     

Prevention of work‐related airway allergies; summary of the advice from the Health Council of the Netherlands

The Health Council of the Netherlands published a report in which the best procedure and method for recommending health‐based occupational exposure limits (OELs) for inhaled allergens were identified by evaluating the scientific state of the art. Many respiratory disorders in the workplace arise from inhalation of substances which can cause allergy. To protect workers against respiratory allergy, various preventive measures are taken, one of them being reduction of exposure by setting legally binding standards. These are based on health‐based OELs that specify a level of exposure to an airborne substance, a threshold level, below which it may reasonably be expected that there is no risk of adverse health effects. The Council is of the opinion that an OEL should prevent against allergic sensitization, as sensitization plays a crucial biological role and is a prerequisite for the development of allergy. Furthermore, the Council considers it most likely that the exposure level below which no allergic sensitization develops for most allergens is so low, that OELs are difficult to set with the current knowledge and technical feasibilities. An alternative approach is to accept exposure, which carries a small predefined risk in developing allergic sensitization. In addition, it is worth considering periodic screening of exposed workers on allergic sensitization, because timely intervention can prevent worse. The feasibility of periodic screening and what else is needed to comply with the most important criteria, should however be judged case‐by‐case.     

Frequency of antigen-specific B cells during experimental ocular Chlamydia trachomatis infection.

Chlamydia-specific antibody-secreting cells have been identified in conjunctiva and draining cervical lymph nodes by an ELISPOT assay in a cynomolgus monkey model of trachoma. These local sites contained numbers of chlamydia-specific B cells that were higher than those in distant inguinal lymph nodes and peripheral blood. The numbers of chlamydia-specific immunoglobulin G-secreting B cells observed were 5 to 57 per 10(6) cells in conjunctiva and 24 to 996 per 10(6) cells in cervical lymph nodes during conjunctival infection or after challenge of immune monkeys with the chlamydial 57-kDa heat shock protein (hsp60). These studies demonstrate a large chlamydia-specific B-cell component in the conjunctiva during ocular chlamydial infection. These results are similar to our findings for chlamydia-specific T-cell responses.