Intrinsic Dissolution as a Tool for Evaluating Drug Solubility in Accordance with the Biopharmaceutics Classification System

The Biopharmaceutics Classification System (BCS) is a tool that was created to categorize drugs into different groups according to their solubility and permeability characteristics. Through a combination of these factors and physiological parameters, it is possible to understand the absorption behavior of a drug in the gastrointestinal tract, thus contributing to cost and time reductions in drug development, as well as reducing exposure of human subjects during in vivo trials. Solubility is attained by determining the equilibrium under conditions of physiological pH, while different methods may be employed for evaluating permeability. On the other hand, the intrinsic dissolution rate (IDR), which is defined as the rate of dissolution of a pure substance under constant temperature, pH, and surface area conditions, among others, may present greater correlation to the in vivo dissolution dynamic than the solubility test. The purpose of this work is to discuss the intrinsic dissolution test as a tool for determining the solubility of drugs within the scope of the Biopharmaceutics Classification System (BCS).

Neural response telemetry in patients with the double-array cochlear implant

This study aimed to evaluate the neural response in double-array cochlear implant as well as to describe the refractory recovery and the spread of excitation functions. In a prospective study 11 patients were implanted with the double-array cochlear implant. Neural response telemetry (NRT) was performed intra-operatively. NRT threshold could be registered in 6 of the 11 patients, at least in one electrode. The remaining five patients did not show measurable neural response intra-operatively. It was noted that although recovery and spread of excitation functions could be recorded in all the tested electrodes with measurable neural responses, the responses were shown to be different from the usual register in patients with other etiologies.

Phylogenetic relationships in Kumanoa (Batrachospermales, Rhodophyta) species in Brazil with the proposal of Kumanoa amazonensis sp nov.

This Study evaluated the species-level taxonomy and phylogenetic relationship among Kumanoa species from Brazil with other regions of the world based on the plastid-encoded RUBISCO large Subunit gene (rhcL). Partial rbcL sequences were obtained for 11 Kulnanoa specimens. Eight species are recognised from Brazil on the basis of molecular and morphological data: seven previously described (K abilii, K ambignia, K. breviarticulata, K. cipoensis, K. equisetoidea, K. globospora and K procarpa) and a new species here proposed (K. amazonensis sp. nov. Necchi & Vis). The new species has reduced and dense whorls but differs from the two closest related species in lacking secondary fascicles. Previously proposed infrageneric categories were not supported by the molecular data. Species described and endemic (K. breviarticulata, K. cipoensis, K equiseloidea and K. procarpa) to Brazil are not grouped together but are variously related to other species from North America, Europe and Australasia. With the species recognised in this study using molecular and morphological data and those previously distinguished by morphology, 13 species of Kumanoa are Currently documented from Brazil.

Antioxidant enzyme activity in Acidithiobacillus ferrooxidans LR maintained in contact with chalcopyrite

The total protein content and activity of the enzymes glutathione reductase (GR), superoxide dismutase (SOD) and thioredoxin reductase (TrxR) were evaluated in Acidithiobacillus ferrooxidans LR cells maintained in contact with the metal sulfide chalcopyrite for 1 and 10 days. A significant decrease in total protein content was observed in cells maintained for 10 days in the presence of chalcopyrite, suggesting proteolytic breakdown clue to exposure to the metal sulfide. Following 10 clays of contact with chalcopyrite, increases in GR, SOD and TrxR activities were detected, suggesting the formation of reactive oxygen species. After ten clays, there was a fivefold increase in GR activity, of which, isoenzyme IV represented approximately 82% of the total. An increase in Fe-SOD activity following ten days exposure to chalcopyrite was also determined, as measured on non-denaturing polyacrylamide gels. Also, after 10 days. an approximately 31-fold increase was observed for TrxR activity. The presence of oxidative stress when A. ferrooxidans is in the presence of chalcopyrite could have a negative impact on bioleaching. (C) 2010 Elsevier Ltd. All rights reserved.

HFE gene mutations in patients with primary iron overload: Is there a significant improvement in molecular diagnosis yield with HFE sequencing?

Rare HFE variants have been shown to be associated with hereditary hemochromatosis (HH), an iron overload disease. The low frequency of the HFE p.C282Y mutation in HH-affected Brazilian patients may suggest that other HFE-related mutations may also be implicated in the pathogenesis of HH in this population. The main aim was to screen for new HFE mutations in Brazilian individuals with primary iron overload and to investigate their relationship with HH. Fifty Brazilian patients with primary iron overload (transferrin saturation >50% in females and 60% in males) were selected. Subsequent bidirectional sequencing for each HFE exon was performed. The effect of HFE mutations on protein structure were analyzed by molecular dynamics simulation and free binding energy calculations. p.C282Y in homozygosis or in heterozygosis with p.H63D were the most frequent genotypic combinations associated with HH in our sample population (present in 17 individuals, 34%). Thirty-six (72.0%) out of the 50 individuals presented at least one HFE mutation. The most frequent genotype associated with HH was the homozygous p.C282Y mutation (n = 11, 22.0%). One novel mutation (p.V256I) was indentified in heterozygosis with the p.H63D mutation. In silico modeling analysis of protein behavior indicated that the p.V256I mutation does not reduce the binding affinity between HFE and beta 2-microglobulin ((beta 2M) in the same way the p.C282Y mutation does compared with the native HFE protein. In conclusion, screening of HFE through direct sequencing, as compared to p.C282Y/p.H63D genotyping, was not able to increase the molecular diagnosis yield of HH. The novel p.V256I mutation could not be implicated in the molecular basis of the HH phenotype, although its role cannot be completely excluded in HH-phenotype development. Our molecular modeling analysis can help in the analysis of novel, previously undescribed, HFE mutations. (C) 2010 Elsevier Inc. All rights reserved.

Intra- and interspecific divergence in the nuclear sequences of the clock gene period in species of the Drosophila buzzatii cluster

We have measured nucleotide variation in the CLOCK/CYCLE heterodimer inhibition domain (CCID) of the clock X-linked gene period in seven species belonging to the Drosophila buzzatii cluster, namely D. buzzatii, Drosophila koepferae, Drosophila antonietae, Drosophila serido, Drosophila gouveai, Drosophila seriema and Drosophila borborema. We detected that the purifying selection is the main force driving the sequence evolution in period, in agreement with the important role of CCID in clock machinery. Our survey revealed that period provides valuable phylogenetic information that allowed to resolve phylogenetic relationships among D. gouveai, D. borborema and D. seriema, which composed a polytomic clade in preliminary studies. The analysis of patterns of intraspecific variation revealed two different lineages of period in D. koepferae, probably reflecting introgressive hybridization from D. buzzatii, in concordance with previous molecular data.

Influence of respiratory biofeedback associated to re-expansive ventilation patterns in individuals with functional mouth breathing

Objectives: Assess the effect of re-expansive respiratory patterns associated to respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength and habits in individuals with functional mouth breathing (FMB). Methods: Sixty children with FMB were divided into experimental and control groups. The experimental group was submitted to 15 sessions of re-expansive respiratory patterns associated to RBF (biofeedback pletsmovent; MICROHARD (R) V1.0), which provided biofeedback of the thoracic and abdominal movements. The control group was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static respiratory pressure measurements and questions regarding habits (answered by parents/guardians) were carried out before and after therapy. The Student`s t-test for paired data and non-parametric tests were employed for statistical analysis at a 5% Level of significance. Results: Significant changes were found in forced vital. capacity, Tiffeneau index scores, maximum expiratory pressure, maximum inspiratory pressure and habits assessed in FMB with the use of RBF associated to the re-expansive patterns. No significant differences were found comparing the experimental and control groups. Conclusions: The results allow the conclusion that RBF associated to re-expansive patterns improves forced vital capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB and can therefore be used as a form of therapy for such individuals. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

A high-fat meal impairs muscle vasodilatation response to mental stress in humans with Glu27 beta(2)-adrenoceptor polymorphism

Background: Forearm blood flow responses during mental stress are greater in individuals homozygous for the Glu27 allele. A high-fat meal is associated with impaired endothelium-dependent dilatation. We investigated the impact of high-fat ingestion on the muscle vasodilatory responses during mental stress in individuals with the Glu27 allele and those with the Gln27 allele of the beta(2)-adrenoceptor gene. Methods: A total of 162 preselected individuals were genotyped for the Glu27Gln beta(2)-adrenoceptor polymorphism. Twenty-four individuals participated in the study. Fourteen were homozygous for the Gln27 allele (Gln27Gln, 40 +/- 2 years; 64 +/- 2 kg), and 10 were homozygous for the Glu27 allele (Glu27Glu, 40 +/- 3 years; 65 +/- 3 kg). Forearm blood flow was evaluated by venous occlusion plethysmography before and after ingestion of 62 g of fat. Results: The high-fat meal caused no changes in baseline forearm vascular conductance (FVC, 2.2 +/- 0.1 vs. 2.4 +/- 0.2; P = 0.27, respectively), but reduced FVC responses to mental stress (1.5 +/- 0.2 vs. 0.8 +/- 0.2 units; P = 0.04). When volunteers were divided according to their genotypes, baseline FVC was not different between groups (Glu27Glu = 2.4 +/- 0.1 vs. Gln27Gln = 2.1 +/- 0.1 units; P = 0.08), but it was significantly greater in Glu27Glu individuals during mental stress (1.9 +/- 0.4 vs. 1.0 +/- 0.3 units; P = 0.04). High-fat intake eliminated the difference in FVC responses between Glu27Glu and Gln27Gln individuals (FVC, 1.3 +/- 0.4 vs. 1.2 +/- 0.4; P = 0.66, respectively). Conclusion: These findings demonstrate that a high-fat meal impairs muscle vasodilatation responses to mental stress in humans. However, this reduction can be attributed to the presence of the homozygous Glu27 allele of the beta(2)-adrenoceptor gene.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Destiny and will, religion and politics: Jesus Society and Enlightenment in the posthumous Malabar Rites controversy

The first presentation of Antoine-Marin Le Mierre`s tragedy Malabar Widow, or the Empire of Customs, took place in 1770. It was based on the famous controversy over the Malabar (south west India) Rites. The object of the controversy was the Jesuit project in India, which started in the beginning of XVII century and was stopped by the Pope Benedict XIV, with the Apostolic Constitution Omnium Sollicitudinum. The papal condemnation of the rites closed a long process which shows the progressive loss of power of the Jesuit Company in the Age of Enlightenment, which will be definitive in 1773, with the suppression of the Company. In Le Mierre`s tragedy, we find the judgment of Malabar rites according to the rationalist ideas of the Enlightenment, with some typical topoi of the philosophes`s cultural perspective. At the same time, the enlightened disputation reproduces the Jesuit internal debate about India itself. Starting from a religious universal perspective of the different strategies of Christianization in India, or in the entire East, the missionary controversy had been about the religious or political interpretation of local signs. Briefly, this polemic would turn into the controversy on the rites. The criticism to the Jesuitical strategy of mission, in XVII and XVIII centuries, would start from here. The enormous number of documents on this issue became a powerful instrument in the battle against the Jesuits, in the XVIII century. On the base of the missionary disputation, the Enlightenment constructs the proposal of a new political and humanistic universal perspective. According to this, eventuality, the religion becomes just a privileged instrument to realize this operation.

Morphodigital study of bone quality in the mandibular angle in patients with third molar impacted

The aim of this study was to analyze if the presence of impacted third molars, and their positions in the mandibular angle, can change the bone quality in this area, considering the measure of the cortical thickness in this region as representative or not for mandible fracture risk. Software was used to analyze 50 digital images from panoramic radiographs of patients who had one or two impacted third molars in the mandible, and 30 digital images of patients with agenesis of the mandibular third molar. The thickness of the cortical region of the mandible was measured; it was possible to draw a parallel line to the posterior portion of the mandible and a parallel line to the body of this bone on each side of the image. At the intersection of these lines near the distal portion of the second molar, another line was set up to serve as reference in the cortical thickness measurement. It could be concluded that the cortical thickness of the mandibular angle in male patients without impacted third molars was greater than the thickness in patients with these teeth, and no difference in thickness was found for the female group.

Electromyographic activity of masticatory muscles in women with osteoporosis

The purpose of this study was to analyze the electromyographic (EMG) activity and the maximal molar bite force in women diagnosed with osteoporosis in the maxillary and mandibular regions, considering the habits and conditions that lead to development of generalized skeletal bone loss, including on face bones, can disturb the functional harmony of the stomatognathic system. Twenty-seven women with mandibular and maxillary osteoporosis and 27 healthy controls volunteered to participate in the study. A 5-channel electromyographer was used. Muscle activity was evaluated by means of EMG recordings of the masticatory musculature (masseter and temporalis muscles, bilaterally) during the following clinical conditions: rest (5 s); right and left lateral excursions (5 s); protrusion (5 s); maximal dental clenching on Parafilm™ (4 s) and maximal voluntary contraction (4 s). This latter clinical condition was used as the normalization factor of the sample data. It was observed that individuals with osteoporosis presented greater EMG activity when maintaining mandible posture conditions and less activity during dental clenching and when obtaining maximal molar bite force. It may be concluded that facial osteoporosis can interfere on the patterns of masticatory muscle activation and maximal bite force of the stomatognathic system.

Acupuncture for the prevention of radiation-induced xerostomia in patients with head and neck cancer

The aim of this study was to evaluate the effectiveness of acupuncture in minimizing the severity of radiation-induced xerostomia in patients with head and neck cancer. A total of 24 consecutive patients receiving > 5000 cGy radiotherapy (RT) involving the major salivary glands bilaterally were assigned to either the preventive acupuncture group (PA, n = 12), treated with acupuncture before and during RT, or the control group (CT, n = 12), treated with RT and not receiving acupuncture. After RT completion, clinical response was assessed in all patients by syalometry, measuring the resting (RSFR) and stimulated (SSFR) salivary flow rates, and by the visual analogue scale (VAS) regarding dry mouth-related symptoms. Statistical analyses were performed with repeated-measures using a mixed-effect modeling procedure and analysis of variance. An alpha level of 0.05 was accepted for statistical significance. Although all patients exhibited some degree of impairment in salivary gland functioning after RT, significant differences were found between the groups. Patients in the PA group showed improved salivary flow rates (RSFR, SSFR; p < 0.001) and decreased xerostomia-related symptoms (VAS, p < 0.05) compared with patients in the CT group. Although PA treatment did not prevent the oral sequelae of RT completely, it significantly minimized the severity of radiation-induced xerostomia. The results suggest that acupuncture focused in a preventive approach can be a useful therapy in the management of patients with head and neck cancer undergoing RT.

Microlithiasis of the gallbladder: role of endoscopic ultrasonography in patients with idiopathic acute pancreatitis

OBJECTIVES: Causes may be found in most cases of acute pancreatitis, however no etiology is found by clinical, biological and imaging investigations in 30% of these cases. Our objective was to evaluate results from endoscopic ultrasonography (EUS) for diagnosis of gallbladder microlithiasis in patients with unexplained (idiopathic) acute pancreatitis. METHODS: Thirty-six consecutive non-alcoholic patients with diagnoses of acute pancreatitis were studied over a five-year period. None of them showed signs of gallstones on transabdominal ultrasound or tomography. We performed EUS within one week of diagnosing acute pancreatitis. Diagnosis of gallbladder microlithiasis on EUS was based upon findings of hyperechoic signals of 0.5-3.0 mm, with or without acoustic shadowing. All patients (36 cases) underwent cholecystectomy, in accordance with indication from the attending physician or based upon EUS diagnosis. RESULTS: Twenty-seven patients (75%) had microlithiasis confirmed by histology and nine did not (25%). EUS findings were positive in twenty-five. Two patients had acute cholecystitis diagnosed at EUS that was confirmed by surgical and histological findings. In two patients, EUS showed cholesterolosis and pathological analysis disclosed stones not detected by EUS. EUS diagnosed microlithiasis in four cases not confirmed by surgical treatment. In our study, sensitivity, specificity and positive and negative predictive values to identify gallbladder microlithiasis (with 95% confidence interval) were 92.6% (74.2-98.7%), 55.6% (22.7-84.7%), 86.2% (67.4-95.5%) and 71.4% (30.3-94.9%), respectively. Overall EUS accuracy was 83.2%. CONCLUSIONS: EUS is a very reliable procedure to diagnose gallbladder microlithiasis and should be used for the management of patients with unexplained acute pancreatitis. This procedure should be part of advanced endoscopic evaluation.

Vancomycin use in a brazilian teaching hospital: comparison with the Hospital Infection Controlpractices Advisory Committee Guidelines (HICPAC)

This study describes vancomycin prescribing patterns in an average complexity hospital and compare the guidelines proposed by the Hospital Infection Control Practices Advisory Committee (HICPAC). The study was conducted in a 256-bed secondary-care hospital. Data were collected of all patients given vancomycin from March 2003 to February 2004, using a standardized chart-extraction form designed. Appropriate and inappropriate use was reviewed according to the Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines on prudent vancomycin use. Out of 118 prescriptions, 95 (80.5%) were considered appropriate. Out of these 95 orders, 77 (81.1%) were administered for empiric treatment of suspected Gram-positive infections, 17 (17.9%) were administered for treatment of proven Gram-positive infections (76.5% identified as Staphyloccocus aureus-like agents) and 1 (1.0%) for beta-lactam allergy. The majority of the patients (96.6%) had recently used an antimicrobial medication (3 months). The mean pre-treatment hospitalization period was 11±10 days. Out of the 118 treatments, 67 (56.8%) were for nosocomial infections. The more frequent indications for vancomycin use were pneumonia (48.3%) and primary sepsis (18.6%), accounting for more than 66% of all treatments. No restriction policy was suggested because vancomycin use was considered adequate in the majority of the treatment cases. The broad empiric use of this antimicrobial was greater than expected in the institution and its use should be revised.