Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes.

OBJECTIVE: Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of reactive oxygen species (ROS) levels and chondrocyte survival under pathological conditions. METHODS: Human chondrocytes were from the unaffected area of knee OA cartilage (n = 12) and were stimulated with IL-1ß to mimic pathological conditions. Mitochondrial membrane depolarization and ROS levels were determined using specific dyes and flow cytometry. Autophagy was determined by Western blotting for ATG5, Beclin1, immunofluorescence staining and confocal microscopy. Gene expression was determined by RT-qPCR. siRNA, wild-type and mutant Parkin plasmids were transfected using Amaxa system. Apoptosis was determined by PI staining of chondrocytes and TUNEL assay. RESULTS: IL-1ß-stimulated OA chondrocytes showed high levels of ROS generation, mitochondrial membrane damage, accumulation of damaged mitochondria and higher incidence of apoptosis. IL-1ß stimulation of chondrocytes with depleted Parkin expression resulted in sustained high levels of ROS, accumulation of damaged/dysfunctional mitochondria and enhanced apoptosis. Parkin translocation to depolarized/damaged mitochondria and recruitment of p62/SQSTM1 was required for the elimination of damaged/dysfunctional mitochondria in IL-1ß-stimulated OA chondrocytes. Importantly we demonstrate that Parkin elimination of depolarized/damaged mitochondria required the Parkin ubiquitin ligase activity and resulted in reduced ROS levels and inhibition of apoptosis in OA chondrocytes under pathological conditions. CONCLUSIONS: Our data demonstrates that Parkin functions to eliminate depolarized/damaged mitochondria in chondrocytes which is necessary for mitochondrial quality control, regulation of ROS levels and chondrocyte survival under pathological conditions.

Advances of polyolefins from fiber to nanofiber: fabrication and recent applications.

Polyolefins are a widely accepted commodity polymer made from olefinic monomer consisting of carbon and hydrogen. This thermoplastic polymeric material is formed through reactive double bonds of olefins by the addition polymerization technique and it possesses a diverse range of unique features for a large variety of applications. Among the various types, polyethylene and polypropylene are the prominent classes of polyolefins that can be crafted and manipulated into diversified products for numerous applications. Research on polyolefins has boomed tremendously in recent times owing to the abundance of raw materials, low cost, lightweight, high chemical resistance, diverse functionalities, and outstanding physical characteristics. Polyolefins have also evidenced their potentiality as a fiber in micro to nanoscale and emerged as a fascinating material for widespread high-performance use. This review aims to provide an elucidation of the breakthroughs in polyolefins, namely as fibers, filaments, and yarns, and their applications in many domains such as medicine, body armor, and load-bearing industries. Moreover, the development of electrospun polyolefin nanofibers employing cutting-edge techniques and their prospective utilization in filtration, biomedical engineering, protective textiles, and lithium-ion batteries has been illustrated meticulously. Besides, this review delineates the challenges associated with the formation of polyolefin nanofiber using different techniques and critically analyzes overcoming the difficulties in forming functional nanofibers for the innovative field of applications.

Course of insight in manic episode.

BACKGROUND: Insight is an important factor associated with non compliance and poor outcome. Poor level of insight has been described as a characteristic in patients with acute bipolar disorder with more unawareness in social consequences with increasing severity in manic episode. AIM: Main aim of study was to see the baseline and longitudinal relationship between dimensions of insight with improvement in psychopathology. SETTING AND DESIGN: Forty four patients diagnosed with mania, were selected from an inpatient setting at Institute of Mental Health and Hospital, Agra with mean age of 31.07(±9.00) years. They were assessed at base line and were followed up weekly or psychopathology and insight. MATERIALS AND METHODS: The Young's mania rating scale for psychopathology and insight was assessed on three dimensions of SUMD. RESULTS: Twenty five patients eventually completed the study. There was a positive correlation with global insight and with psychopathology consistent in longitudinal follow-up (P<0.05), but not correlating for awareness for achieved effect of medication and social consequences. Linear regression showed a positive relationship at the first and second week of assessment of SUMD and YMRS scores (P=0.001; 0.019). CONCLUSION: Improvement in insight is graded in a manic episode as compared to psychopathology. There is slower improvement in awareness of social consequences of mental disorder. It means that improvement in psychopathology may not necessarily indicate remission and need further supervision to improve insight and hence monitoring.

Emotional and Behavioural Changes in Children and Adolescents and Their Association With Parental Depression During COVID-19 Pandemic: a Pilot Study in Bangladesh.

OBJECTIVE: The COVID-19 pandemic has affected the mental health of children, adolescents, and their parents. This study aimed to assess the emotional and behavioural changes in children and adolescents and their association with parental depression during the COVID-19 pandemic in Bangladesh. METHODS: On 7 May 2020 during COVID-19 lockdown, an online questionnaire was distributed through social media and made available for 10 days. Data were collected from parents of children aged 4 to 17 years. The Bangla version of the parent-rated version of the Strengths and Difficulties Questionnaire (SDQ) was used to determine the behavioural and emotional disturbances of the children and adolescents. The Bangla version of the Patient Health Questionnaire (PHQ-9) was used to assess the depression status of parents. RESULTS: There were 512 participants. 21.5% of children and adolescents had emotional and behavioural problems. More boys than girls had abnormal peer relationship problems (21.1% vs 15.4%, p = 0.03). Of the parents, 16.2% had moderate depression, 5.5% moderately severe depression, and 2.9% severe depression. 8.2% and 2.9% of parents reported that it was very difficult and extremely difficult, respectively, to do work, take care of things at home, or get along with other people; the proportion was higher in mothers than fathers (χ2 = 11.4, df = 3, p = 0.01). The PHQ-9 total score of parents mildly correlated with the SDQ score of children and adolescents (r = 0.51, p = 0.01). In multiple linear regression, a combination of parent sex (ß = 0.08, p < 0.001), child's history of developmental/psychiatric problems (ß = 0.02, p = 0.67), and the SDQ total score of children and adolescents (ß = 0.52, p = 0.03) accounted for 27% of the variability in PHQ total score of parents. CONCLUSION: During lockdown, the prevalence of psychiatric disorder among children and adolescents and their parents increased. The depression status of parents mildly correlated with the behavioural and emotional disturbances of children and adolescents. We recommend opening the schools as soon as the situation improves and developing interventions such as virtual mental health assessment for children and adolescents and their parents.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential.

Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Characterization of microbial antifreeze protein with intermediate activity suggests that a bound-water network is essential for hyperactivity.

Antifreeze proteins (AFPs) inhibit ice growth by adsorbing onto specific ice planes. Microbial AFPs show diverse antifreeze activity and ice plane specificity, while sharing a common molecular scaffold. To probe the molecular mechanisms responsible for AFP activity, we here characterized the antifreeze activity and crystal structure of TisAFP7 from the snow mold fungus Typhula ishikariensis. TisAFP7 exhibited intermediate activity, with the ability to bind the basal plane, compared with a hyperactive isoform TisAFP8 and a moderately active isoform TisAFP6. Analysis of the TisAFP7 crystal structure revealed a bound-water network arranged in a zigzag pattern on the surface of the protein's ice-binding site (IBS). While the three AFP isoforms shared the water network pattern, the network on TisAFP7 IBS was not extensive, which was likely related to its intermediate activity. Analysis of the TisAFP7 crystal structure also revealed the presence of additional water molecules that form a ring-like network surrounding the hydrophobic side chain of a crucial IBS phenylalanine, which might be responsible for the increased adsorption of AFP molecule onto the basal plane. Based on these observations, we propose that the extended water network and hydrophobic hydration at IBS together determine the TisAFP activity.

Fish-Derived Antifreeze Proteins and Antifreeze Glycoprotein Exhibit a Different Ice-Binding Property with Increasing Concentration.

The concentration of a protein is highly related to its biochemical properties, and is a key determinant for its biotechnological applications. Antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs) are structurally diverse macromolecules that are capable of binding to embryonic ice crystals below 0 °C, making them useful as protectants of ice-block formation. In this study, we examined the maximal solubility of native AFP I-III and AFGP with distilled water, and evaluated concentration dependence of their ice-binding property. Approximately 400 mg/mL (AFP I), 200 mg/mL (AFP II), 100 mg/mL (AFP III), and >1800 mg/mL (AFGP) of the maximal solubility were estimated, and among them AFGP's solubility is much higher compared with that of ordinary proteins, such as serum albumin (~500 mg/mL). The samples also exhibited unexpectedly high thermal hysteresis values (2-3 °C) at 50-200 mg/mL. Furthermore, the analysis of fluorescence-based ice plane affinity showed that AFP II binds to multiple ice planes in a concentration-dependent manner, for which an oligomerization mechanism was hypothesized. The difference of concentration dependence between AFPs and AFGPs may provide a new clue to help us understand the ice-binding function of these proteins.

Depression among multidrug-resistant tuberculosis patients in Punjab, Pakistan: a large cross-sectional study.

BACKGROUND AND OBJECTIVES: Depression is likely to be a factor in the low global rates of successful treatment for multidrug-resistant tuberculosis (MDR-TB) due to poor adherence to treatment. We aimed to estimate the prevalence of depression among patients being treated for MDR-TB in Pakistan, explore rates of depression over the course of treatment and identify risk factors for depression. DESIGN: This cross-sectional study analysed health care service data from 12 treatment sites following a single screening event using the Patient Health Questionnaire 9 (PHQ-9). Logistic regression models were used to identify associations. RESULTS: Data were collected from 1279 patients with MDR-TB. The proportion of MDR-TB patients with depression was 42.8% (95%CI 40.1-45.5). Rates of depression varied according to duration of treatment, with the highest proportion (53.2%) found in those who were in months 10-12 of treatment. The odds of depression in women were higher than for men (adjusted odds ratio [aOR] 1.84, 95%CI 1.46-2.33). The odds of depression were higher in patients living in concrete-built houses than in those living in mud-built houses (aOR 1.37, 95%CI 1.03-1.82). CONCLUSION: Depression is common in MDR-TB patients, and should be screened for and treated within MDR-TB treatment programmes.

Did diabetes mellitus affect treatment outcome in drug-resistant tuberculosis patients in Pakistan from 2010 to 2014?

Settings: All hospitals managing drug-resistant tuberculosis (DR-TB) according to national guidelines in Pakistan. Objectives: To assess the effect of diabetes mellitus (DM) and factors associated with unfavourable outcomes in DR-TB. Methods: A cross-sectional study based on a retrospective record review of patients enrolled on DR-TB treatment from 2010 to 2014 in Pakistan. DR-TB data reported to Pakistan's National TB Control Programme on a monthly basis were used for the study. Result: Among 5811 patients enrolled on second-line drugs, 8.8% had DM. Overall, 68.9% had favourable outcomes. No association was found between DM and DR-TB treatment outcomes (risk ratio 0.90, 95%CI 0.74-1.05). Unfavourable outcomes were more frequent among DR-TB patients with human immunodeficiency virus (HIV) co-infection (OR 11.58, 95%CI 2.20-60.72), extensively drug-resistant TB patients (OR 5.36, 95%CI 1.00-28.72), patients with exposure to both first-line and second-line anti-tuberculosis drugs (OR 2.45, 95%CI 1.21-4.97) and those with a previous history of treatment in the private sector (OR 1.53, 95%CI 1.16-2.02). Conclusion: Although there were limitations to correctly measuring DM and its management, DM appears not to be a risk factor for unfavourable outcomes in DR-TB patients in our study. DR-TB and HIV co-infection, second-line drug resistance and history of treatment in the private sector were nevertheless more frequently associated with adverse outcomes.

Contexte : Tous les hôpitaux prenant en charge la tuberculose pharmacorésistante (TB-DR) selon les directives nationales du Pakistan.Objectif : Evaluer l'effet du diabète (DM) et les facteurs associés à un résultat défavorable du traitement de la TB-DR.Méthode : Etude transversale basée sur une revue rétrospective de dossiers de patients enrôlés dans un traitement de TB-DR de 2010 à 2014 au Pakistan. Les registres de TB-DR envoyés au programme national de lutte contre la TB chaque mois ont été utilisés pour l'étude.Résultats : Parmi 5811 patients enrôlés dans un traitement par médicaments de deuxième ligne, 8,8% avaient un DM. Dans l'ensemble, 68,9% ont eu des résultats favorables. Il n'a pas été trouvé d'association entre le DM et le résultat du traitement de la TB-DR (ratio de risque 0,90 ; IC95% 0,74­1,05). Les facteurs associés à des résultats défavorables sont la coinfection par TB-DR et le virus de l'immunodéficience humaine (VIH) (OR 11,58 ; IC95% 2,20­60,72), la TB ultrarésistante (OR 5,36 ; IC95% 1,00­28,72), l'exposition à la fois aux médicaments de première ligne et de deuxième ligne (OR 2,45 ; IC95% 1,21­4,97) et des antécédents de traitement dans le secteur privé (OR 1,53 ; IC95% 1,16­2,02).Conclusion : Dans notre étude, avec ses limites en termes de mesures correctes du DM et de sa prise en charge, le DM ne semble pas être un facteur de risque de résultat défavorable pour les patients TB-DR. Par contre, la coinfection TB-DR et VIH, la résistance aux médicaments de deuxième ligne et les antécédents de traitement dans le secteur privé ont été associés à des résultats médiocres.

Marco de referencia: Todos los hospitales que suministran tratamiento contra la tuberculosis farmacorresistente (TB-DR) en el marco de las directrices nacionales de Pakistán.Objetivo: Evaluar el efecto de la diabetes (DM) sobre el desenlace de la TB-DR y los factores que se asocian con los desenlaces desfavorables.Método: Un estudio transversal realizado a partir del examen retrospectivo de las historias clínicas de los pacientes que iniciaron tratamiento por TB-DR del 2010 al 2014 en el Pakistán.Métodos: En el presente estudio se consultaron los registros de los casos de TB-DR que se notifican mensualmente al Programa Nacional de control de la Tuberculosis.Resultados: De los 5811 pacientes que iniciaron tratamiento con medicamentos de segunda línea, el 8,8% sufría DM. En general, el 68,9% de los casos alcanzó desenlaces favorables. No se observó ninguna asociación entre la presencia de DM y el desenlace terapéutico de la TB-DR (riesgo relativo 0,90; IC95% 0,74­1,05). Los factores que se asociaron con desenlaces desfavorables fueron la coinfección por el virus de la inmunodeficiencia humana (VIH) y la TB-DR (OR 11,58; IC95% 2,20­60,72), la TB ultrarresistente (OR 5,36; IC95% 1,00­28,72), la exposición a los dos tipos de fármacos, de primera y de segunda línea (OR 2,45; IC95% 1,21­4,97) y el antecedente de tratamiento antituberculoso en el sector privado (OR 1,53; IC95% 1,16­2,02).Conclusión: Según los resultados del presente estudio, pese a algunas limitaciones en la evaluación correcta de la DM y su tratamiento, no pareciera que la presencia de DM fuese un factor de riesgo de resultados desfavorables del tratamiento de pacientes con TB-DR. Sin embargo, la coinfección por el VIH y la TB-DR, la resistencia a fármacos de segunda línea y el antecedente de tratamiento antituberculoso en el sector privado se asociaron con desenlaces desfavorables.

Alarming rates of attrition among tuberculosis patients in public-private facilities in Lahore, Pakistan.

Setting: All public-private mix (PPM) facilities caring for tuberculosis (TB) patients in Lahore city, Pakistan, under four models: PPM1 (general practitioners), PPM2 (non-governmental organisations), PPM3 (private hospitals) and PPM4 (others). Objective: To assess the pre-treatment loss to follow-up (LTFU), defined as patients documented in the laboratory registers but not in the treatment registers of any PPM facility, among sputum smear-positive TB patients diagnosed during January-March 2015, and unfavourable treatment outcomes among patients registered for treatment and associated factors. Design: This was a retrospective cohort study reviewing existing programme records. Poisson regression was used to identify factors associated with outcomes. Results: Of 2473 patients diagnosed, 1590 (64%) were lost to follow-up before treatment. This was higher among males (68%) and the elderly (79%), and lower among 'high positives' (smear grading 2+ or 3+, 53%) and in the PPM1 model (34%). Of 883 patients started on treatment, 165 (19%) had unfavourable outcomes: 8% LTFU, 5% treatment failure, 3% died and 3% not evaluated. Previously treated patients (34%) and children (44%) had the worst outcomes. Conclusion: Pre-treatment LTFU was alarmingly high and requires urgent attention, including the development and institution of mechanisms for patient tracking using information and mobile phone technology, and making TB notification mandatory in the private sector.

Contexte: Toutes les structures mixtes public-privé (PPM) prenant en charge les patients tuberculeux (TB) à Lahore, Pakistan, dans quatre modalités : PPM1 (médecins généralistes), PPM2 (organisations non gouvernementales), PPM3 (hôpitaux privés), PPM4 (autres).Objectif: Evaluer les pertes de vue avant traitement (LTFU), définies comme des patients figurant dans le registre du laboratoire mais pas dans le registre de l'une quelconque des PPM pour leur traitement, parmi les patients ayant eu un diagnostic de TB à frottis positif de janvier à mars 2015 et un résultat défavorable du traitement parmi les patients enregistrés pour leur traitement, ainsi que les facteurs associés.Schéma: Une étude rétrospective de cohorte par revue des dossiers de programme existants. La régression de Poisson a été utilisée pour identifier les facteurs associés aux résultats.Résultats: Sur 2473 patients diagnostiqués, 1590 (64%) ont été perdus de vue avant le traitement. Ce résultat a été plus élevé parmi les hommes (68%) et les patients plus âgés (79%), et plus faible parmi les patients « hautement positifs ¼ (frottis grade 2+ ou 3+, 5%) et dans le modèle de PPM1 (34%). Sur 883 patients ayant mis en route leur traitement, 165 (19%) ont eu un résultat défavorable (8% LTFU, 5% d'échecs du traitement, 3% décédés, 3% non évalués). Les patients déjà traités (34%) et les enfants (44%) ont eu des résultats plus mauvais.Conclusion: Les LTFU avant le traitement ont été élevées de manière alarmante et demandent une attention urgente. Ceci inclut le développement et la mise en œuvre de mécanismes de recherche des patients grâce aux techniques d'information et de téléphonie mobile, et l'obligation de notification de la TB par le secteur privé.

Marco de referencia: Todos los establecimientos de la colaboración público privada (PPM, por public-private mix) que atienden pacientes con tuberculosis (TB) en la ciudad de Lahore, en Pakistán, según cuatro modelos, a saber: PPM1 (médicos generalistas), PPM2 (organizaciones no gubernamentales), PPM3 (hospitales privados) y PPM4 (otros).Objetivo: Examinar las pérdidas durante el seguimiento antes del tratamiento (LTFU), definidas como los pacientes que aparecen en los registros de laboratorio, pero no se encuentran en los registros de tratamiento en ningún establecimiento PPM, de los pacientes con baciloscopia positiva del esputo, diagnosticados de enero a marzo del 2015, evaluar los desenlaces terapéuticos desfavorables en los pacientes registrados en tratamiento y determinar los factores asociados con estos desenlaces.Método: Un estudio retrospectivo de cohortes con análisis de los registros del programa. Mediante una regresión de Poisson se definieron los factores asociados con los criterios de valoración.Resultados: De los 2473 pacientes diagnosticados, 1590 se perdieron durante el seguimiento antes de comenzar el tratamiento (64%). Esta proporción fue más alta en los hombres (68%) y los ancianos (79%) y más baja en los casos con baciloscopia de alta positividad (53%, frotis calificado como 2+ o 3+) y en el modelo PPM1 (34%). De los 883 pacientes que iniciaron tratamiento, 165 (19%) presentaron desenlaces desfavorables (8% LTFU, 5% fracaso terapéutico, 3% fallecieron, 3% no se evaluaron). Los desenlaces más desfavorables se observaron en los pacientes con antecedente de tratamiento antituberculoso (3%) y en los niños (44%).Conclusión: La proporción de LTFU durante el seguimiento antes de iniciar el tratamiento antituberculoso fue muy alarmante y exige una atención urgente. La respuesta puede consistir en la elaboración y aplicación de mecanismos de localización de los pacientes mediante las tecnologías de la información y los teléfonos celulares y la introducción de la notificación obligatoria de la TB en el sector privado.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential / Síntese verde de nanaopartículas de ouro utilizando extratos de tubérculos Delphinium chitralense, sua caracterização e potencial inibitório enzimático

Greeen synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Green synthesis of gold nanaoparticles using Delphinium Chitralense tuber extracts, their characterization and enzyme inhibitory potential

Abstract Green synthesis has been introduced as an alternative to chemical synthesis due to the serious consequences. Metal nanoparticles synthesized through green approach have different pharmaceutical, medical and agricultural applications. The present study followed a green and simple route for the preparation of potentially bioactive gold nanoparticles (Au NPs). Au NPs were prepared via green synthesis approach using crude basic alkaloidal portion of the tuber of Delphinium chitralense. The green synthesized Au NPs were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD) fourier transform infrared (FTIR), and UV-Visible spectrophotometer. Morphological analysis shows that Au NPs have cubic geometry with different sizes. UV-Vis spectroscopic analysis confirmed the synthesis of Au NPs while XRD proved their pure crystalline phase. The Au NPs showed promising dose dependent inhibition of both AChE and BChE as compared to the crude as well as standard drug.

Resumo A síntese verde foi introduzida como uma alternativa à síntese química devido às graves consequências. As nanopartículas metálicas sintetizadas através da abordagem verde têm diferentes aplicações farmacêuticas, médicas e agrícolas. O presente estudo seguiu uma rota verde e simples para a preparação de nanopartículas de ouro potencialmente bioativas (Au NPs). As NPs de Au foram preparadas via abordagem de síntese verde usando a porção alcaloide básica bruta do tubérculo de Delphinium chitralense. As NPs de Au sintetizadas verdes foram caracterizadas por microscopia eletrônica de transmissão (TEM), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), infravermelho com transformada de Fourier (FTIR) e espectrofotômetro UV-Visível. A análise morfológica mostra que as NPs de Au possuem geometria cúbica com tamanhos diferentes. A análise espectroscópica UV-Vis confirmou a síntese de Au NPs enquanto a XRD provou sua fase cristalina pura. O Au NPs mostrou inibição dependente da dose promissora de AChE e BChE em comparação com a droga bruta e padrão.

Essential role of L-arginine uptake and protein tyrosine kinase activity for NO-dependent vasorelaxation induced by stretch, isometric tension and cyclic AMP in rat pulmonary arteries.

1. The NO-dependent component of cyclic AMP-induced vasorelaxation in rat pulmonary arteries is critically dependent on extracellular L-arginine but independent of endothelial cell intracellular [Ca(2+)]. We examined whether L-arginine uptake was also essential for NO production induced by passive stretch or isometric tension, processes also reported to be Ca(2+)-independent. 2. The passive length-tension curve was depressed by physiological concentrations of L-arginine (400 microM; P<0.05). Inhibition of the y(+) transporter with 10 mM L-lysine, NO synthase with L-NAME (100 microM), or protein tyrosine kinase with erbstatin A (30 microM) caused identical upward shifts (P<0.001), alone or in combination. Tyrphostin 23 was similar to erbstatin A, whilst the inactive analogue tyrphostin A1 and genistein were without effect. 3. L-arginine (400 microM) shifted the PGF(2 alpha) concentration-response curve under isometric conditions to the right (P<0.05), whereas L-NAME or L-lysine caused a leftward shift (P<0.001). Tyrphostin 23 (30 microM) more than reversed the L-arginine-induced suppression of PGF(2 alpha)-induced tension; subsequent addition of L-NAME had no effect. The L-lysine-sensitive component of CPT cyclic AMP-induced vasorelaxation was abolished by erbstatin A. 4. ACh-induced vasorelaxation was approximately 80% inhibited by L-NAME, but was not affected by L-lysine or 400 microM L-arginine. Erbstatin A reduced the vasorelaxation by only approximately 25%. 5. We conclude that activation of NO production by stretch, isometric tension, or cyclic AMP in rat pulmonary arteries is critically dependent on the presence and uptake of physiological concentrations of extracellular L-arginine, and protein tyrosine kinase activity. This directly contrasts with ACh-induced vasorelaxation, which was independent of extracellular L-arginine, and relatively unaffected by tyrosine kinase inhibition.

Visual outcome and prognostic factors after vitrectomy for posterior segment foreign bodies.

PURPOSE: To identify the prognostic factors that predict final visual outcome in eyes with posterior segment intraocular foreign body (IOFB) injuries managed by primary pars plana vitrectomy. METHODS: Ninety-six consecutive patients with posterior segment IOFB injuries were retrospectively reviewed. Factors analyzed included initial visual acuity (VA), time between injury and presentation, site of entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, endophthalmitis, location and size of IOFB, use of scleral buckling and/or an encircling band, gas tamponade, lensectomy, number of surgical procedures, and development of retinal detachment. Data were analyzed using univariate and multivariate logistic regression analysis. RESULTS: After a mean follow-up of 8.6 months, 63 eyes (65.6%) achieved VA of 20/200 or better, and 9 eyes (9.4%) had total retinal detachment complicated by inoperable proliferative vitreoretinopathy. On univariate analysis, predictors of poor vision (hand movements or less) were poor initial VA, corneoscleral entrance wound, uveal prolapse, vitreous prolapse, traumatized iris, and development of retinal detachment. In contrast, predictors of good visual outcome (20/200 or better) were absence of uveal prolapse, no endophthalmitis, and no retinal detachment. Multivariate analysis identified corneoscleral entrance wound, uveal prolapse, and development of retinal detachment as the only factors significantly associated with poor visual outcome. Absence of uveal prolapse was the only factor significantly associated with good visual outcome. CONCLUSIONS: Final visual outcome is greatly determined by the severity of the primary injury. On multivariate analysis, significant predictive factors of final VA were corneoscleral entrance wound, presence or absence of uveal prolapse, and development of retinal detachment.

Update on screening for type 2 diabetes. The why, who, how, and what of testing and diagnosing.

Type 2 diabetes can cause serious complications even as it remains undiagnosed. Screening is recommended only in people with risk factors for the disease. The ADA recommends FPG as the test of choice, but RPG is also a practical alternative because it is easier and more convenient. Frequency of rescreening if the first screen result is normal depends on the number of risk factors present. Physicians should realize the importance of a confirmatory test and not base a diagnosis of diabetes on a single value unless the value is so high that the diagnosis is unequivocal.

Klinefelter's syndrome with unelevated serum gonadotropin levels (a case report).

Two cases of Klinefelter's syndrome with 47 XXY karyotype associated with unelevated follicular stimulating hormone (FSH) and luteinizing hormone (LH) levels are reported. The literature is briefly reviewed.