Evaluation of the inhibition effect of thiolated poly(acrylates) on vaginal membrane bound aminopeptidase N and release of the model drug LH-RH

The purpose of this study was to evaluate the inhibitory effect of thiolated carbopol 974P (carb-cys) on the enzymatic activity of vaginal aminopeptidase N in-vitro. Mediated by a carbodiimide, L-cysteine was covalently linked to carbopol 974P. Depending on the weight ratio of polymer to cysteine during the coupling reaction, resulting conjugates displayed 31.3-54.4 micromol thiol groups per g polymer. The inhibitory effect of carb-cys conjugates was evaluated towards isolated aminopeptidase N and aminopeptidase-N-like activity of excised vaginal mucosa covered with native mucus, respectively. Enzymatic activity was assayed spectrophotometrically using L-leucine-p-nitroanilide (L-leu-pNA) as a synthetic substrate. Carb-cys thereby showed a significantly higher inhibitory effect than unmodified polymer towards both isolated enzyme and vaginal mucosa. Moreover, enzyme inhibition was strongly dependent on the amount of thiol groups being immobilised. The more thiol groups available the higher was the inhibitory effect. Due to its additional high cohesive properties and the possibility of a sustained drug release, which could be shown for the model drug LH-RH, carb-cys appears interesting for the development of vaginal peptide drug-delivery systems.     

Synthesis and effects on chloroquine susceptibility in Plasmodium falciparum of a series of new dihydroanthracene derivatives

To suggest a mechanism of action for drugs capable to reverse the chloroquine resistance, a new set of 9,10-dihydro-9,10-ethano and ethenoanthracene derivatives was synthesized and compounds were tested with the aim to assess their effect on chloroquine susceptibility in Plasmodium falciparum resistant strains. With respect to this, reversal of resistance and change in drug accumulation were compared. Structure-activity relationship and molecular modeling studies made it possible to define a pharmacophoric moiety for reversal agents and to propose a putative model of interaction with some selected amino acids.     

Investigation of the effects of concomitant caffeine administration on the metabolic disposition of pyrazinamide in rats

The utility of pyrazinamide (PZA) in the short-course antituberculous treatment is well established. All available data support the idea that the PZA metabolite pyrazinoic acid (PA) is the active compound against M. tuberculosis. This situation warranted a deeper investigation of possible interactions with respect to its metabolic disposition. Caffeine, which is widely used as a drug and is a common constituent of most diets, shares with PZA the same metabolic enzyme, xanthine oxidase (XO). This study investigated if, and in what manner, concomitant administration of caffeine affects PZA metabolism. PZA and caffeine, in various doses (PZA=50 or 100 mg kg(-1) and caffeine= 0, 50, 100, and 150 mg kg(-1)), were administered to female Sprague-Dawley rats. PZA and its three main metabolites were quantified in 24 h urine samples by reversed phase-HPLC Concomitant administration of 100 mg kg(-1) caffeine and 50 mg kg(-1) PZA increased from the excretion (p<0.05) of the most water-soluble and the least toxic PZA metabolite 5-hydroxypyrazinoic acid (5-OH-PA) from 66.18+/-10.87 to 94.56+/-8.65 micromol/24 h. This effect was more pronounced when 100 mg kg(-1) of PZA was administered increasing excretion of 5-OH-PA from 113.28+/-70 to 173.23+/-17.82 micromol/24 h. These results show that the metabolic disposition of PZA is affected by concomitant caffeine intake.     

Multilevel surgery in spastic diplegia: evaluation by physical examination and gait analysis in 25 children

Gait improvement surgery was performed on 25 ambulatory children with the diplegic type of cerebral palsy. Multiple soft tissue and bony procedures were performed (mean 8.2 procedures) according to criteria defined on the basis of physical examination and gait analysis. Relevant physical examination findings and kinematic and kinetic data in the sagittal plane were evaluated before surgery and at least 3 years after surgery. Physical examination showed a reduction in the ankle plantar-flexor power and in the range of hip flexion and ankle plantarflexion after surgery. Analysis of gait data showed significant improvements in the sagittal plane kinematics and the power generation at the hip and the ankle. At the knee joint there was maintenance of power of the flexor and extensor group of muscles on physical examination, with significant improvements in the kinematics after surgery. The authors conclude that well-selected surgery improves function of the spastic muscle. The importance of assessing clinical, kinematic, and kinetic data together for proper evaluation of gait is stressed.     

Aedes aegypti in Tahiti and Moorea (French Polynesia): isoenzyme differentiation in the mosquito population according to human population density

Genetic differences at five polymorphic isoenzyme loci were analyzed by starch gel electrophoresis for 28 Aedes aegypti samples. Considerable (i.e., high Fst values) and significant (i.e., P values >10(-4)) geographic differences were found. Differences in Ae. aegypti genetic structure were related to human population densities and to particularities in mosquito ecotopes in both Tahiti and Moorea islands. In highly urbanized areas (i.e., the Papeete agglomeration), mosquitoes were highly structured. Recurrent extinction events consecutive to insecticidal treatments during dengue outbreaks tend to differentiate mosquito populations. In less populated zones (i.e., the east coast of Moorea and Tahiti), differences in ecotope characteristics could explain the lack of differentiation among mosquitoes from rural environments such as the east coast of Tahiti where natural breeding sites predominate. When the lowest populated zones such as Tahiti Iti and the west coast of Moorea are compared, mosquito are less differentiated in Moorea. These results will be discussed in relation to the recent findings of variation in mosquito infection rates for dengue-2 virus.     

Cardiac rehabilitation in Austria: short term quality of life improvements in patients with heart disease

BACKGROUND: The goal of cardiac rehabilitation programs is not only to prolong life, but also to improve physical functioning, symptoms, wellbeing and health-related quality of life (HRQL). The aim of the study was to document short-term outcomes of cardiac rehabilitation programs in Austria. METHODS: Consecutive patients (N = 487, 64.7% male, age 60.9 +/- 12.5 SD years) after myocardial infarction (MI), with or without percutaneous interventions (PCI), coronary artery bypass grafting (CABG) or heart valve surgery (HVS), referred to the six inpatient rehabilitation centers of the Austrian PVA insurance company, were included in the study. Exercise capacity, risk factors and HRQL (MacNew Heart Disease Quality of Life Instrument [MacNew] and EuroQoL-5D [EQ-5D]) were measured at the beginning and end of the 4-week inpatient cardiac rehabilitation program. RESULTS: Global HRQL (MacNew) improved significantly over time in all patients combined (+0.75 +/- 0.88 SD, T = -16.99, df = 394, p < .001) and exceeded the minimal important difference. Patients with CABG, HVS or MI without PCI showed the greatest improvements in global HRQL after cardiac rehabilitation (p < .02). Blood pressure, cholesterol, triglyceride, body mass index, waist circumference improved significantly (all p < .001). CONCLUSION: These findings provide evidence that the improvements in HRQL and risk factors following cardiac rehabilitation in Austria are clinically important. HRQL should become a standard outcome parameter in cardiac rehabilitation.     

Reduction of sleep bruxism using a mandibular advancement device: an experimental controlled study

PURPOSE: The objective of this experimental study was to compare the effect on sleep bruxism and tooth-grinding activity of a double-arch temporary custom-fit mandibular advancement device (MAD) and a single maxillary occlusal splint (MOS). MATERIALS AND METHODS: Thirteen intense and frequent bruxors participated in this short-term randomized crossover controlled study. All polygraphic recordings and analyses were made in a sleep laboratory. The MOS was used as the active control condition and the MAD was used as the experimental treatment condition. Designed to temporarily manage snoring and sleep apnea, the MAD was used in 3 different configurations: (1) without the retention pin between the arches (full freedom of movement), (2) with the retention pin in a slightly advanced position (< 40%), and (3) with the retention pin in a more advanced position (> 75%) of the lower arch. Sleep variables, bruxism-related motor activity, and subjective reports (pain, comfort, oral salivation, and quality of sleep) were analyzed with analysis of variance and the Friedman test. RESULTS: A significant reduction in the number of sleep bruxism episodes per hour (decrease of 42%, P < .001) was observed with the MOS. Compared to the MOS, active MADs (with advancement) also revealed a significant reduction in sleep bruxism motor activity. However, 8 of 13 patients reported pain (localized on mandibular gums and/or anterior teeth) with active MADs. CONCLUSIONS: Short-term use of a temporary custom-fit MAD is associated with a remarkable reduction in sleep bruxism motor activity. To a smaller extent, the MOS also reduces sleep bruxism. However, the exact mechanism supporting this reduction remains to be explained. Hypotheses are oriented toward the following: dimension and configuration of the appliance, presence of pain, reduced freedom of movement, or change in the upper airway patency.