Comparison of the speed of bronchodilator action after inhaled fenoterol and rimiterol in reversible airways obstruction

Summary

A placebo-controlled study was carried out in 10 patients with reversible airways obstruction to evaluate the speed of action, peak and duration of bronchodilator effect, and effect on heart rate of rimiterol hydrobromide compared with the effects of fenoterol hydrobromide. Both drugs were administered, on successive days, in a dose of 400 μg by inhalation from pressurized aerosols, as was placebo (propellant only). A pressure-volume technique was used which permits repeated measurements of airway resistance with minimum fatigue for the patient. The study clearly demonstrated the difficulties of comparing two bronchodilator aerosols in patients with reversible airways obstruction. Although the differences in airway resistance after placebo inhalation were not significant in themselves, the changes did influence the statistical significance of the changes seen after the active drugs. The results, nevertheless, indicated that both rimiterol and fenoterol produced a comparable and rapid broncho-dilatation, with a significantly better effect on FEV, after rimiterol 3 minutes after inhalation. Fenoterol inhalation was more effective 120 minutes after inhalation. Rimiterol showed no effect on the heart rate compared with a statistically significant increase produced by fenoterol over the first 10 minutes. It is suggested that, in cases where rapid and somewhat shorter duration of bronchodilator effect are required, such as in the acute asthma attack and before sodium cromoglycate, steroid aerosols or exercise, the characteristics of rimiterol would seem to be of value.     

Morphological and molecular alterations at the junctional complex in irradiated human colon adenocarcinoma cells,Caco-2

Purpose: Ionizing radiation is one of the main modalities used in the treatment of colorectal cancer. Despite a number of epigenetic or non-targeted effects of radiation exposure that have been described, the effect of radiation on cell-cell adhesion in the epithelium has been less studied. We report morphological and molecular alterations induced by ionizing radiation at the junctional complex level of human colon cancer Caco-2 cells.

Materials and methods: Cells were irradiated with doses of 2, 5 or 10 Gy and the effects on the junctional complex were monitored for different times after irradiation. Alterations of tight and adherens junction components were observed by measuring the transepithelial electrical resistance, by immunofluorescence and immunoblotting and electron microscopy analyses.

Results: Ionizing radiation caused alterations in the junctional complex, as evidenced by: (a) a decrease in the transepithelial electrical resistance, (b) alterations in the pattern of the distribution of junctional proteins as observed for E-cadherin, occludin, and zonula occludens 1 (ZO-1), but with minor changes in claudin-1 localization, and (c) wide spaces between opposed cells. These effects were dose and time-dependent since minor doses of irradiation caused a reversible effect on E-cadherin distribution and transepithelial electrical resistance.

Conclusions: The results obtained show that ionizing radiation caused redistribution of the main junctional proteins E-cadherin, occludin and ZO-1 with minor changes for claudin-1, leading to disassembly of the junctional complex and loss of its functionality in Caco-2 cells. The molecular mechanisms responsible for these events need further elucidation.     

Environmental and health impact of unrecovered API from pharmaceutical manufacturing wastes: A review of contemporary treatment,recycling and management strategies

Pharmaceutical industries are imminent for the survival of any contemporary society as their products are valuable for the populace's health and wellness. However, the wastes of these industries have become a nuisance with severe implications on human health and ecosystem, especially in many developing countries where they are discharged indiscriminately into the environment, either untreated or poorly treated. Pharmaceutical Manufacturing Waste (PMW) effluents have been reported to possess a high BOD and COD, as well as recoverable APIs of various classes of pharmaceuticals. Moreover, antibiotic residues in these effluents are implicated in the progression and spread of antibiotic resistance in the aquatic and agroecosystem. Globally, the diverse activities of various pharmaceutical industries, owing to their diverse products, have resulted in difficulty in developing universal management and treatment protocols. Consequently, regulatory bodies/institutions find it challenging to monitor waste disposal practices of these industries adequately, primarily owing to their non-disclosure policies of intellectual properties. Hence, to a large extent, the onus for a sustainable society regarding PMWs lies in the decision and policies of these industries. Therefore, this review aims to foster informed policy-making decisions regarding waste management practices of pharmaceutical industries.     

Typing of vancomycin-resistant enterococci with MALDI-TOF mass spectrometry in a nosocomial outbreak setting

ObjectivesTo investigate the usefulness of matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS) typing as a first-line epidemiological tool in a nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VREfm).MethodsFifty-five VREfm isolates, previously characterized by whole-genome sequencing (WGS), were included and analysed by MALDI-TOF MS. To take peak reproducibility into account, ethanol/formic acid extraction and other steps of the protocol were conducted in triplicate. Twenty-seven spectra were generated per isolate, and spectra were visually inspected to determine discriminatory peaks. The presence or absence of these was recorded in a peak scheme.ResultsNine discriminatory peaks were identified. A characteristic pattern of these could distinguish between the three major WGS groups: WGS I, WGS II and WGS III. Only one of 38 isolates belonging to WGS I, WGS II or WGS III was misclassified. However, ten of the 17 isolates not belonging to WGS I, II or III displayed peak patterns indistinguishable from those of the outbreak strain.ConclusionsUsing visual inspection of spectra, MALDI-TOF MS typing proved to be useful in differentiating three VREfm outbreak clones from each other. However, as non-outbreak isolates could not be reliably differentiated from outbreak clones, the practical value of this typing method for VREfm outbreak management was limited in our setting.     

Genotypic resistance test in proviral DNA can identify resistance mutations never detected in historical genotypic test in patients with low level or undetectable HIV-RNA

BackgroundBeyond the detection of resistant HIV strains found in plasma samples, archival HIV-DNA in peripheral blood mononuclear cells (PBMCs) might represent a reservoir of additional resistance.ObjectiveTo characterize the HIV-1 resistance in PBMCs from patients with suppressed or low-level viremia (50–1000 copies/mL) and evaluate its added value compared to the resistance detected in previous plasma genotypic resistance tests (GRTs).Study designHIV-1 infected patients selected for treatment change despite low/undetectable viremia were tested. Number and type of primary resistance mutations (PRMs) detected in PBMCs were compared to those detected in previous plasma GRTs. Logistic regression assessed factors associated with presence of at least one PRM in PBMCs.Result468 patients with a PBMC GRT were analyzed; 149 of them had at least 2 plasma GRTs performed before PBMC genotyping. 42.3% of patients showed at least one PRM in PBMCs. The highest proportion of PRMs in PBMCs was observed for NRTI class (30.6%), followed by NNRTI (22.2%), PI (14.1%) and INI (4.9%). In 20.1% of patients, PRMs were detected only in PBMCs and not in any of the plasma GRT previously performed. By using multivariable analysis, a higher number of previous regimens, injecting drug-use route and a lower nadir CD4 were associated with significantly higher risk of detecting PRMs in PBMCs.ConclusionOur findings support the usage of PBMC GRT in addition to the current recommended plasma RNA test, especially when therapeutic and/or resistance information is not available.     

Correlation between time lag of arterial–plethysmographic waveforms and systemic vascular resistance: a prospective study

Blood pressure (BP), a surrogate of cardiac output (CO), is also dependent on systemic vascular resistance (SVR). But SVR is not routinely monitored in daily clinical practice. We hypothesise that the time difference between the peripheral arterial waveform and the finger plethysmographic waveform (time lag index - TLi) could indicate the systemic vascular resistance. In this study, we correlated TLi with the systemic vascular resistance measured by minimally invasive CO monitor (pulse contour analysis). SVR changes in response to administration of mannitol were studied. American Society of Anesthesiologists (ASA) class I and II patients undergoing major intracranial surgeries were recruited. Arterial cannulation and pulse-oximetry recordings were done in the same limb. Arterial and plethysmographic waveforms were recorded before mannitol infusion (baseline) and at every 10 minutes for 60 minutes after the termination of mannitol infusion. Simultaneously, SVR was recorded from the Vigileo FLotrac CO monitor. Using custom-made programme, the time difference between both waveforms was calculated and corrected for heart rate (TLi). The correlation between time lag and the systemic vascular resistance was assessed using a mixed effect model, adjusting for the subject. Data of one hundred subjects were analysed. Following mannitol administration, there was a significant decrease in the SVR and the TLi (p?β?=?877.16, p?=?.008). The high beta coefficient suggests that when SVR increases, the TLi also increase and vice versa. A strong correlation between SVR and TLi was demonstrated for a given patient. Further studies are needed to explore the possibility of utilising this parameter to follow up changes in SVR in an individual patient at a particular point in time in different clinical scenarios.     

Intermittent resistance exercise and obesity,considered separately or combined,impair spermatic parameters in adult male Wistar rats

Obesity and absence of physical exercise are global problems that affect concentration and sperm quality in the male reproductive system. The purpose of this study was to examine the effect of obesity and resistance training, considered separately or in association, on testicular function and reproductive capacity. Twenty pubertal male Wistar rats were distributed into four groups: control (C) and exercise (E) groups that received standard rat chow; and obese (O) and obese with exercise (OE) groups that received a high‐fat diet. All the groups received filtered water during the experimental conditions. Groups E and OE were submitted to 8 weeks of high‐intensity intermittent training. Afterwards, testes were collected for sperm count, spermatogenic kinetics, histopathology, morphometry and immunodetection of androgen receptors (AR). The vas deferens was collected for sperm morphology. The results showed that obesity increased body weight, naso‐anal length, liver and epididymal fat weight, abnormal spermatozoa and immunodetectable AR. Intermittent exercise decreased daily sperm production (DSP), sperm count and normal spermatozoa, whereas the number of tubules with immunodetectable AR increased. The combination of obesity and intermittent training led to reduced sperm count and DSP, although abnormal spermatozoa and the number of tubules with immunodetectable AR increased. Thus, in conclusion, both obesity and resistance training impaired testicular function during puberty in rats; and this type of exercise has also been shown to be detrimental to testicular physiology.