Chiral HPLC analysis of venlafaxine metabolites in rat liver microsomal preparations after LPME extraction and application to an in vitro biotransformation study

A three-phase LPME (liquid-phase microextraction) method for the enantioselective analysis of venlafaxine (VF) metabolites (O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) in microsomal preparations is described for the first time. The assay involves the chiral HPLC separation of drug and metabolites using a Chiralpak AD column under normal-phase mode of elution and detection at 230 nm. The LPME procedure was optimized using multifactorial experiments and the following optimal condition was established: sample agitation at 1,750 rpm, 20 min of extraction, acetic acid 0.1 mol/L as acceptor phase, 1-octanol as organic phase and donor phase pH adjustment to 10.0. Under these conditions, the mean recoveries were 41% and 42% for (-)-(R)-ODV and (+)-(S)-ODV, respectively, and 47% and 48% for (-)-( R)-NDV and (+)-( S)-NDV, respectively. The method presented quantification limits of 200 ng/mL and it was linear over the concentration range of 200-5,000 ng/mL for all analytes. The validated method was employed to study the in vitro biotransformation of VF using rat liver microsomal fraction. The results demonstrated the enantioselective biotransformation of VF.

Mercury speciation in seafood samples by LC-ICP-MS with a rapid ultrasound-assisted extraction procedure: Application to the determination of mercury in Brazilian seafood samples

This paper describes a simple method for mercury speciation in seafood samples by LC-ICP-MS with a fast sample preparation procedure. Prior to analysis, mercury species were extracted from food samples with a solution containing mercaptoethanol, L-cysteine and HCl and sonication for 15 min. Separation of mercury species was accomplished in less than 5 min on a C8 reverse phase column with a mobile phase containing 0.05%-v/v mercaptoethanol, 0.4% m/v L-cysteine and 0.06 mol L(-1) ammonium acetate. The method detection limits were found to be 0.25, 0.20 and 0.1 ng g(-1) for inorganic mercury, ethylmercury and methylmercury, respectively. Method accuracy is traceable to Certified Reference Materials (DOLT-3 and DORM-3) from the National Research Council Canada (NRCC). With the proposed method there is a considerable reduction of the time of sample preparation. Finally, the method was applied for the speciation of mercury in seafood samples purchased from the Brazilian market. (C) 2010 Elsevier Ltd. All rights reserved.

Stability property of matchings is a natural solution concept in coalitional market games

Stability of matchings was proved to be a new cooperative equilibrium concept in Sotomayor (Dynamics and equilibrium: essays in honor to D. Gale, 1992). That paper introduces the innovation of treating as multi-dimensional the payoff of a player with a quota greater than one. This is done for the many-to-many matching model with additively separable utilities, for which the stability concept is defined. It is then proved, via linear programming, that the set of stable outcomes is nonempty and it may be strictly bigger than the set of dual solutions and strictly smaller than the core. The present paper defines a general concept of stability and shows that this concept is a natural solution concept, stronger than the core concept, for a much more general coalitional game than a matching game. Instead of mutual agreements inside partnerships, the players are allowed to make collective agreements inside coalitions of any size and to distribute his labor among them. A collective agreement determines the level of labor at which the coalition operates and the division, among its members, of the income generated by the coalition. An allocation specifies a set of collective agreements for each player.

The pareto-stability concept is a natural solution concept for discrete matching markets with indifferences

In a decentralized setting the game-theoretical predictions are that only strong blockings are allowed to rupture the structure of a matching. This paper argues that, under indifferences, also weak blockings should be considered when these blockings come from the grand coalition. This solution concept requires stability plus Pareto optimality. A characterization of the set of Pareto-stable matchings for the roommate and the marriage models is provided in terms of individually rational matchings whose blocking pairs, if any, are formed with unmatched agents. These matchings always exist and give an economic intuition on how blocking can be done by non-trading agents, so that the transactions need not be undone as agents reach the set of stable matchings. Some properties of the Pareto-stable matchings shared by the Marriage and Roommate models are obtained.

Quantification of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples by stir bar-sorptive extraction and liquid chromatography

A sensitive and reproducible stir bar-sorptive extraction and high-performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of carbamazepine, carbamazepine-10,11-epoxide, phenytoin and phenobarbital in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. Important factors in the optimization of SBSE efficiency such as pH, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) assured recoveries ranging from 72 to 86%, except for phenytoin (62%). Separation was obtained using a reverse phase C-18 column with UV detection (210 nm). The mobile phase consisted of water: acetonitrile (78:22, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.08-40.0 mu g mL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125-40.0 mu g mL(-1) for phenytoin, The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.0, 4.0 and 20.0 mu g mL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8% and all inter-CVs were less than 10%. Limits of quantification were 0.08 mu g mL(-1) for carbamazepine, carbamazepine-10,11-epoxide and phenobarbital and 0.125 mu g mL(-1) for phenytoin. No interference of the drugs normally associated with antiepileptic drugs was observed. Based on figures of merit results, the SBSE/HPLC-UV proved adequate for antiepileptic drugs analyses from therapeutic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method. (c) 2008 Elsevier B.V. All rights reserved.

Simultaneous analysis of parabens in cosmetic products by stir bar sorptive extraction and liquid chromatography

A sensitive and precise stir bar sorptive extraction (SBSE) combined with LC (SBSE/LC) analysis is described for simultaneous determination of methyl, ethyl, propyl, and butyl parabens in commercial cosmetic products in agreement with the European Union Cosmetics Directive 76/768/EEC. Important factors in the optimization of SB SE efficiency are discussed, such as time and temperature of extraction, pH, and ionic strength of the sample, matrix effects, and liquid desorption conditions by different modes (magnetic stirring, ultrasonic). The LOQs of the SBSE/LC method ranged from 30 to 200 ng/mg, with linear response over a dynamic range, from the LOQ to 2.5 mu g/mg, with a coefficient of determination higher than 0.993. The interday precision of the SBSE/LC method presented a coefficient of variation lower than 5%. The effectiveness of the proposed method was proven for analysis of commercial cosmetic products such as body creams, antiperspirant creams, and sunscreens.

Rifampicin determination in plasma by stir bar-sorptive extraction and liquid chromatography

A sensitive and reproducible stir bar-sorptive extraction and high performance liquid chromatography-UV detection (SBSE/HPLC-UV) method for therapeutic drug monitoring of rifampicin in plasma samples is described and compared with a liquid:liquid extraction (LLE/HPLC-UV) method. This miniaturized method can result in faster analysis, higher sample throughput, lower solvent consumption and less workload per sample while maintaining or even improving sensitivity. Important factors in the optimization of SBSE efficiency such as pH, temperature, extraction time and desorption conditions (solvents, mode magnetic stir, mode ultrasonic stir, time and number of steps) were optimized recoveries ranging from 75 to 80%. Separation was obtained using a reverse phase C(8) column with UV detection (254 nm). The mobile phase consisted of methanol:0.25 N sodium acetate buffer, pH 5.0 (58:42, v/v). The SBSE/HPLC-UV method was linear over a working range of 0.125-50.0 mu g mL(-1). The intra-assay and inter-assay precision and accuracy were studied at three concentrations (1.25, 6.25 and 25.0 mu g mL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 10% and all inter-CVs were less than 10%. Limits of quantification were 0.125 mu g mL(-1). Stability studies showed rifampicin was stable in plasma for 12 h after thawing; the samples were also stable for 24 h after preparation. Based on the figures of merit results, the SBSE/HPLC-UV proved to be adequate to the rifampicin analyses from therapeutic to toxic levels. This method was successfully applied to the analysis of real samples and was as effective as the LLE/HPLC-UV method. (C) 2009 Elsevier B.V. All rights reserved.

Evaluating SVM and MLDA in the extraction of discriminant regions for mental state prediction

Pattern recognition methods have been successfully applied in several functional neuroimaging studies. These methods can be used to infer cognitive states, so-called brain decoding. Using such approaches, it is possible to predict the mental state of a subject or a stimulus class by analyzing the spatial distribution of neural responses. In addition it is possible to identify the regions of the brain containing the information that underlies the classification. The Support Vector Machine (SVM) is one of the most popular methods used to carry out this type of analysis. The aim of the current study is the evaluation of SVM and Maximum uncertainty Linear Discrimination Analysis (MLDA) in extracting the voxels containing discriminative information for the prediction of mental states. The comparison has been carried out using fMRI data from 41 healthy control subjects who participated in two experiments, one involving visual-auditory stimulation and the other based on bimanual fingertapping sequences. The results suggest that MLDA uses significantly more voxels containing discriminative information (related to different experimental conditions) to classify the data. On the other hand, SVM is more parsimonious and uses less voxels to achieve similar classification accuracies. In conclusion, MLDA is mostly focused on extracting all discriminative information available, while SVM extracts the information which is sufficient for classification. (C) 2009 Elsevier Inc. All rights reserved.

Organ-Sparing Microsurgical Resection of Incidental Testicular Tumors Plus Microdissection for Sperm Extraction and Cryopreservation in Azoospermic Patients: Surgical Aspects and Technical Refinements

INTRODUCTION The management of nonpalpable testicular masses is a challenging task, and coexisting infertility can further complicate the treatment decisions. We present our technique for microsurgical organ-sparing resection of incidental nonpalpable testicular nodules combined with microdissection for testicular sperm extraction and tissue cryopreservation in azoospermic patients. TECHNICAL CONSIDERATIONS Five infertile patients with azoospermia presented with nonpalpable hypoechoic testicular masses that were detected by Ultrasonography and underwent organ-sparing surgery. The testis was delivered through an inguinal incision, and the blood circulation was interrupted with a vascular clamp placed on the spermatic cord. Sludged ice was used to prevent warm ischemia, and a temperature probe was used to control the temperature at 12 degrees-15 degrees C. Real-time reflex ultrasonography was used to locate the tumor, and a stereotaxic hook-shaped needle was inserted under ultrasound guidance. The needle was placed adjacent to the tumor to guide the microsurgical resection. The tunica albuginea was incised over the tumor, which was dissected and removed, along with the adjoining parenchymal tissue. Frozen section studies were performed and, if malignancy was confirmed, biopsies of the tumor cavity margins and remaining parenchyma were obtained to ensure the absence of residual tumor. Microdissection was performed for excision of selected enlarged tubules that were processed and cryopreserved. CONCLUSIONS We present a technique for microsurgical organ-sparing resection of testicular tumor and sperm extraction that can be used in selected infertile patients with azoospermia in whom incidental masses have been diagnosed by ultrasonography. This conservative approach should be especially considered for patients with a solitary testis or bilateral tumors. UROLOGY 73: 887-892, 2009. (C) 2009 Elsevier Inc.

Pentafecta: A New Concept for Reporting Outcomes of Robot-Assisted Laparoscopic Radical Prostatectomy

Background: Widespread use of prostate-specific antigen screening has resulted in younger and healthier men being diagnosed with prostate cancer. Their demands and expectations of surgical intervention are much higher and cannot be adequately addressed with the classic trifecta outcome measures. Objective: A new and more comprehensive method for reporting outcomes after radical prostatectomy, the pentafecta, is proposed. Design, setting, and participants: From January 2008 through September 2009, details of 1111 consecutive patients who underwent robot-assisted radical prostatectomy performed by a single surgeon were retrospectively analyzed. Of 626 potent men, 332 who underwent bilateral nerve sparing and who had 1 yr of follow-up were included in the study group. Measurements: In addition to the traditional trifecta outcomes, two perioperative variables were included in the pentafecta: no postoperative complications and negative surgical margins. Patients who attained the trifecta and concurrently the two additional outcomes were considered as having achieved the pentafecta. A logistic regression model was created to evaluate independent factors for achieving the pentafecta. Results and limitations: Continence, potency, biochemical recurrence-free survival, and trifecta rates at 12 mo were 96.4%, 89.8%, 96.4%, and 83.1%, respectively. With regard to the perioperative outcomes, 93.4% had no postoperative complication and 90.7% had negative surgical margins. The pentafecta rate at 12 mo was 70.8%. On multivariable analysis, patient age (p = 0.001) was confirmed as the only factor independently associated with the pentafecta. Conclusions: A more comprehensive approach for reporting prostate surgery outcomes, the pentafecta, is being proposed. We believe that pentafecta outcomes more accurately represent patients` expectations after minimally invasive surgery for prostate cancer. This approach may be beneficial and may be used when counseling patients with clinically localized disease. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

An easy method for handling the genus Phoneutria (Araneae, Ctenidae) for venom extraction

This paper describes an easy, cheap, and safe method of capturing and handling the medically important spider Phoneutria for venom extraction. The method does not injure or kill the spider and allows the extraction of pure venom.

Histological and histomorphometrical alterations of the periodontal ligament in gerbils submitted to teeth extraction

This study verified the effect of unilateral teeth extraction on the periodontal ligament in gerbils (Meriones unguiculatus). Ten adult male gerbils weighing about 50 g had induced occlusal alterations by upper left molar extractions while the other ten animals, only submitted to surgical stress, were considered as controls. The periodontal ligament was characterized by qualitative and quantitative analysis, histological description and histomorphometric quantification. Significant alterations were observed on the left side of the experimental group (P < 0.05), the hypofunctional region, when it was compared with the contralateral side and the corresponding region of the control group. Two months after occlusal alterations induced by unilateral teeth extraction, atrophic histological alterations and a decrease in the periodontal space on the ipsilateral side characterized the periodontal ligament. In this study it was possible to conclude that the gerbil can be used in experimental models attempting to correlate the periodontium`s biological response to various mechanical stresses, as the periodontal ligament was shown to be highly sensitive to occlusal alterations.

Bone crestal height and bone density after third-molar extraction and grafting: a long-term follow-up study

The objective of this study was to evaluate the long-term influence of xenogenic grafts on bone crestal height and radiographic density following extraction of teeth. The right and left third lower molars of 22 patients were surgically extracted, and one randomly chosen socket was filled with a xenogenic graft (Gent-Tech). The contralateral molar was left to heal naturally, serving as a paired control. Digital intraoral radiographies were taken at surgery and 2, 6, and 24 months after, to evaluate bone density (BD) and alveolar bone crest to cementoenamel junction distance. The data obtained were subjected to two-way analysis of variance and Tukey`s test (alpha = 0.05). The significant decrease in cementoenamel junction distance observed for both groups was limited to the first 6 months. BD values increased significantly in the first 6 months, with no alterations observed up to 24 months for both groups. BD was higher for the experimental group at all time points (p < 0.05). Socket grafting with the xenogenic materials tested did not changed bone crestal height and bone radiographic density in the long term.

Orthodontic-surgical treatment of Class III malocclusion with extraction of an impacted canine and multi-segmented maxillary surgery

Establishment of a treatment plan is based on efficacy and easy application by the clinician, and acceptance by the patient. Treatment of adult patients with Class III malocclusion might require orthognathic surgery, especially when the deformity is severe, with a significant impact on facial esthetics. Impacted teeth can remarkably influence treatment planning, which should be precise and concise to allow a reasonably short treatment time with low biologic cost. We report here the case of a 20-year-old man who had a skeletal Class III malocclusion and impaction of the maxillary right canine, leading to remarkable deviation of the maxillary midline; this was his chief complaint. Because of the severely deviated position of the impacted canine, treatment included extraction of the maxillary right canine and left first premolar for midline correction followed by leveling, alignment, correction of compensatory tooth positioning, and orthognathic surgery to correct the skeletal Class III malocclusion because of the severe maxillary deficiency. This treatment approach allowed correction of the maxillary dental midline discrepancy to the midsagittal plane and establishment of good occlusion and optimal esthetics. (Am J Orthod Dentofacial Orthop 2010;137:840-9)

Strategic maxillary second-molar extraction in Class II malocclusion

Maxillary second-molar extraction in Class II malocclusion is a controversial issue in orthodontics. This treatment protocol is rigorous and not routine. In this case report, we present the orthodontic treatment of a patient with a Class II malocclusion, maxillary crowding, and no mandibular first molars, treated with extraction of the maxillary second molars. The mechanotherapy and indications of maxillary second- molar extraction are discussed. (Am J Orthod Dentofacial Orthop 2009;136:878-86)