Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Evaluación de la eficacia de fosfomicina trometamol y gentamicina en la profilaxis de la cistoscopia flexible tras el estudio de los patógenos de nuestro entorno / Evaluation of the Efficacy of Fosfomycin Trometamol and Gentamicin in the Prophylaxis of Flexible Cystoscopy after the Study of Microflora in our Environment

Objetivo Optimizar el uso de antibióticos en la profilaxis de la cistoscopia flexible estudiando los patógenos más frecuentes de nuestro entorno y eligiendo el antibiótico según sus antibiogramas. Métodos Desde Enero del 2015 hasta Noviembre del 2015, se analizaron los urinocultivos de nuestra área, se eligió el antibiótico en función a su sensibilidad frente a los patógenos más frecuentes y se comparó con un antibiótico de amplio espectro. Desde Enero del 2016 hasta Diciembre del 2016, se realizaron las cistoscopias agrupando a los pacientes en: Grupo 1: Pacientes sin profilaxis; Grupo 2: Profilaxis con Gentamicina 240 mg; Grupo 3: Profilaxis con antibiótico seleccionado. Como variables principales se definieron la presencia de bacteriuria asintomática e ITU tras la realización de la cistoscopia flexible. Resultados Se analizaron 8.530 urinocultivos y se eligió la Fosfomicina Trometamol 3 gr como profilaxis. Se realizaron 244 cistoscopias distribuidas: Grupo 1: 86 (35%); Grupo 2: 72 (30%); Grupo 3: 86 (35%). Se detectó bacteriuria asintomática postcistoscopia en 6 pacientes (2,5%) en el Grupo 1, 7 pacientes (2,9%) en el grupo 2 y 5 pacientes (2%) en el grupo 3 no presentando diferencias significativas (p 0.120). Desarrollaron ITUs postcistoscopia 1 paciente (0,4%) en el Grupo 1, 5 pacientes (2%) en el Grupo 2 y 2 pacientes (0,8%) en el Grupo 3 sin diferencias significativas (p 0.105). Conclusión La Fosfomicina es tan efectiva como la Gentamicina en la profilaxis de la cistoscopia. Para un uso correcto de los antibióticos, se recomienda el estudio de los patógenos de nuestro entorno.

Objective To optimize the use of antibiotics in the prophylaxis of flexible cystoscopy by studying the most frequent pathogens in our environment and choosing the antibiotic according to its antibiograms. Method Between January 2015 and November 2015, urine cultures were analyzed in our area, the antibiotic was chosen based on its sensitivity to the most frequent pathogens and compared with a broad spectrum antibiotic. From January 2016 to December 2016, cystoscopy was performed by grouping patients into: Group 1 - Patients without prophylaxis, Group 2 - Prophylaxis with 240 mg gentamicin, Group 3 - Selected antibiotic prophylaxis. The main variables were the presence of asymptomatic bacteriuria and UTI after flexible cystoscopy. Results 8530 urine cultures were analyzed and 3 g of fosfomycin trometamol was chosen as the prophylactic. There were 244 cystoscopies: Group 1: 86 (35%); Group 2: 72 (30%); Group 3: 86 (35%). Asymptomatic bacteriuria was detected in 6 patients (2.5%) in Group 1, 7 patients (2.9%) in Group 2 and 5 patients (2%) in Group 3, showing no significant differences (p = 0.120). Post-cystoscopic urinary tract infection developed in 1 patient (0.4%) in Group 1, 5 patients (2%) in Group 2 and 2 patients (0.8%) in Group 3, which showed no significant differences (p 0.105). Conclusion Fosfomycin is as effective as Gentamicin as a prophylactic in cystoscopy. The study of the pathogens in each environment is recommended to correctly prescribe the antibiotic.

Effects of heme oxygenase-1 upregulation on isoproterenol-induced myocardial infarction

The present study was designed to examine the effect of heme oxygenase-1 (HO-1) induction by cobalt protoporphyrin (CoPP) on the cardiac functions and morphology, electrocardiogram (ECG) changes, myocardial antioxidants (superoxide dismutase [SOD] and glutathione [GSH]), and expression of heat shock protein (Hsp) 70 and connexin 43 (Cx-43) in myocardial muscles in isoproterenol (ISO) induced myocardial infarction (MI). Thirty two adult male Sprague Dawely rats were divided into 4 groups (each 8 rats): normal control (NC) group, ISO group: received ISO at dose of 150 mg/kg body weight intraperitoneally (i.p.) for 2 successive days; ISO + Trizma group: received (ISO) and Trizma (solvent of CoPP) at dose of 5 mg/kg i.p. injection 2 days before injection of ISO, with ISO at day 0 and at day 2 after ISO injections; and ISO + CoPP group: received ISO and CoPP at a dose of 5 mg/kg dissolved in Trizma i.p. injection as Trizma. We found that, administration of ISO caused significant increase in heart rate, corrected QT interval, ST segment, cardiac enzymes (lactate dehydrogenase, creatine kinase-muscle/brain), cardiac HO-1, Hsp70 with significant attenuation in myocardial GSH, SOD, and Cx-43. On the other hand, administration of CoPP caused significant improvement in ECG parameters, cardiac enzymes, cardiac morphology; antioxidants induced by ISO with significant increase in HO-1, Cx-43, and Hsp70 expression in myocardium. In conclusions, we concluded that induction of HO-1 by CoPP ameliorates ISO-induced myocardial injury, which might be due to up-regulation of Hsp70 and gap junction protein (Cx-43).

Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues / Liposomes as potential carriers for ketorolac ophthalmic delivery: formulation and stability issues

ABSTRACT Drug delivery to treat ocular disorders locally is a challenging endeavor. Traditional ocular dosage form - eye drops - exhibits poor availability, consequently inefficient therapeutic response. The objective of the study was to formulate and characterize a ketorolac tromethamine ocular system with a prolonged release pattern based on liposomes as a vesicular carrier and to design once daily liquid preparation realizing the thermal in situ gelation principle. Liposomes were prepared by film hydration method. The influence of cholesterol concentration, pH and volume of hydration medium, and type and concentration of charging imparting agents were studied. Liposomes were characterized via, morphological examination, vesicular size, and encapsulation efficiency, and in vitro release performance, moreover its stability was assessed. The results obtained highlighted that liposomes showed a closed vesicular multi-lamellar structure. Ketorolac was successfully encapsulated within the liposomal structure in a cholesterol and charge inducing agent concentration-dependent behaviour. The dispersion of liposomes within thermosensitive Poloxamer in situ gel was able to retard the release of the drug by diffusion providing a controlled prolonged delivery. The liposomal formulations were physically stable for six months. Ketorolac tromethamine in situ liposomal gel representing an efficient alternative in terms of ocular retention and patient compliance when compared with conventional eye drops.

The Effects of Vascular Endothelial Growth Factor on Capsule Formation around Silicone Implant in Rats

BACKGROUND: The purpose of this study was to examine the effects of a single administration of vascular endothelial growth factor (VEGF) in promoting the angiogenesis and thereby reducing the formation of capsular contracture. METHODS: We treated 24 female Sprague-Dawley rats with (1) 5 mM Tris Buffer and 150 mM NaCl 0.1 cc, (2) VEGF 15 µg/0.1 cc, (3) VEGF 150 µg/0.1 cc during placement of the implant, or (4) VEGF 150 µg/0.1 cc and VEGF 300 µg/0.2 cc. We histopathologically measured the thickness of the capsule and the number of blood vessels. RESULTS: All experimental groups had a significant difference in the thickness of the capsule compared to the control group (P<0.001). There was no significant difference between experimental group 2 and experimental group 3. The number of blood vessels formed around the capsule was significantly greater in all the experimental groups compared with the control group (P<0.05). There was no significant difference between the experimental groups. There was a significant negative correlation between the thickness of the capsule and the number of blood vessels (Spearman's correlation coefficient, 0.2732; P<0.0001). CONCLUSIONS: A single administration of VEGF reduced formation of the capsule and increased the vascularity around the implant, supporting the hypothesis that prevention of tissue ischemia can be a treatment strategy for capsular contracture.

Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock

PURPOSE: To evaluate whether post-hemorrhagic shock mesenteric lymph (PSML) is involved in cardiac dysfunction induced by hemorrhagic shock. METHODS: The hemorrhagic shock model (40±2 mmHg, 3h) was established in rats of the shock and shock+drainage groups; and PSML drainage was performed from hypotension 1-3h in the shock+drainage rats. Then, the isolated hearts were obtained from the rats for the examination of cardiac function with Langendorff system. Subsequently, the isolated hearts were obtained from normal rats and perfused with PSML or Krebs-Henseleit solution, and the changes of cardiac function were observed. RESULTS: The left ventricular systolic pressure (LVSP) and the maximal rates of LV developed pressure (LVDP) rise and fall (±dP/dt max) in the shock and shock+drainage groups were lower than that of the sham group; otherwise, these indices in the shock+drainage group were higher compared to the shock group. In addition, after isolated hearts obtained from normal rats perfusing with PSML, these cardiac function indices were gradual decline along with the extension of time, such as heart rate, LVSP, ±dP/dt max, etc. CONCLUSION: Post-hemorrhagic shock mesenteric lymph is an important contributor to cardiac dysfunction following hemorrhagic shock. .

Preservation with high-pressure carbon monoxide better protects ex vivo rabbit heart function than conventional cardioplegic solution preservation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of high-pressure carbon monoxide for preservation of ex vivo rabbit heart graft in comparison with the conventional HTK cardioplegic solution preservation.</p><p><b>METHODS</b>Heart grafts isolated from 85 New Zealand rabbits were randomly divided into Naive group (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8, 10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for 30 min with a modified Langendorff apparatus and examined for left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia score (AS), myocardial ultrestructure, and cardiac enzyme profiles.</p><p><b>RESULTS</b>After preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and diastolic functions were significantly better in CO group than in HTK group, but these differences were not obvious between the two groups after graft preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures occurred in the isolated hearts after a 24-h preservation in both CO and HTK groups, but the myocardial damages were milder in CO group.</p><p><b>CONCLUSION</b>Preservation using high-pressure carbon monoxide can better protect isolated rabbit heart graft than the conventional HTK preservation approach especially for prolonged graft preservation.</p>

Factors affecting the success of resynchronization protocols with or without progesterone supplementation in dairy cows

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.

In vitro activity of fosfomycin tromethamine against extended spectrum beta-lactamase producing urinary tract bacteria

To determine the in vitro activity of Fosfomycin tromethamine against extended spectrum beta-lactamase producing uropathogens. Experimental study. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from October 2011 to October 2012. A total of 381 culture positive ESBL producing isolates from 2400 urine samples submitted over a period of one year were included in this study. Identification of isolates was done by standard biochemical profile of the organisms. The antimicrobial susceptibility of culture positive isolates was performed by disk diffusion method as recommended by Clinical Laboratory Standard Institute guidelines [CLSI]. The antimicrobial activity of Fosfomycin to various isolates revealed that 93% of E. coli, 64% Klebsiella spp. 50% Proteus spp. 75% Enterobacter cloacae, 100% Citrobacter freundii, 100% Burkholderia spp. 100% Serratia spp. and 50% Stenotrophomonas maltophilia were susceptible to this chemical compound. Fosfomycin showed excellent effectiveness to most of the common ESBL producing bacteria such as E. coli, Klebsiella and Proteus spp

Bloqueio dos nervos ilioinguinal e ílio-hipogástrico com dexcetoprofeno intravenoso melhora a analgesia após histerectomia abdominal / Ilioinguinal-iliohypogastric nerve block with intravenous dexketoprofen improves postoperative analgesia in abdominal hysterectomies / Bloqueo de los nervios ilioinguinal e ilio-hipogástrico con dexketoprofeno intravenoso mejora la analgesia después de la histerectomía abdominal

JUSTIFICATIVA E OBJETIVO: O objetivo deste estudo foi avaliar os efeitos da aplicação intravenosa(IV) de dexcetoprofeno trometamol em bloqueio dos nervos ilioinguinal e ílio-hipogástrico na qualidade analgésica e no consumo de morfina após histerectomia abdominal total. MÉTODO: Estudo clínico controlado e randomizado conduzido com 61 pacientes. O estudo foi feito em sala de operação, sala de recuperação pós-anestésica e ambulatório. Os 61 pacientes foram randomicamente alocados em três grupos: grupo controle (Grupo C), grupo bloqueio (Grupo B) e grupo bloqueio com dexcetoprofeno (Grupo BD). Antes da incisão cirúrgica feita após a indução da anestesia, fizemos o bloqueio dos nervos ilioinguinal e ilio-hipogástrico (Grupo C recebeu solução salina e grupos B e BD receberam levobupivacaína). Em contraste com os grupos C e B, o Grupo BD recebeu dexcetoprofeno. Administramos morfina a todos os pacientes para analgesia, com o uso do método de analgesia controlada pelo paciente (ACP) durante o pós-operatório de 24 horas. Registramos os escores para dor pela escala visual analógica (EVA), os índices de satisfação, o consumo de morfina e os efeitos colaterais durante o pós-operatório de 24 horas. RESULTADOS: Os escores EVA do Grupo BD foram menores do que os dos grupos C e B no pós-operatório (p < 0,05) nos intervalos de 1, 2, 6 e 12 horas. Os escores EVA do Grupo C foram maiores do que os do Grupo B nas primeiras 2 horas de pós-operatório. O tempo até a primeira demanda de ACP foi mais longo, os valores de consumo de morfina mais baixos e os índices de satisfação maiores no Grupo BD do que nos outros dois grupos (p < 0,05). CONCLUSÃO: O bloqueio dos nervos ilioinguinal e ílio-hipogástrico com dexcetoprofeno IV aumenta a satisfação do paciente e diminui o consumo de opioides e sugere que dexcetoprofeno trometamol é um analgésico anti-inflamatório não esteroide eficaz em analgesia pós-operatória.

BACKGROUND AND OBJECTIVE: In this study, our aim was to evaluate the effects of intravenous dexketoprofen trometamol with ilioinguinal and iliohypogastric nerve block on analgesic quality and morphine consumption after total abdominal hysterectomy operations. METHODS: We conducted this randomized controlled clinical study on 61 patients. The study was conducted in the operation room, post-anesthesia care unit, and inpatient clinic. We randomly grouped the 61 patients into control group (group C), block group (group B) and dexketoprofen-block group (group DB). Before the skin incision performed after anesthesia induction, we performed ilioinguinal iliohypogastric block (group C given saline and group P and DB given levobupivacaine). In contrast to group C and B, group DB was given dexketoprofen. We administered morphine analgesia to all patients by patient-controlled analgesia (PCA) during the postoperative 24 hours. We recorded Visual Analogue Scale (VAS), satisfaction scores, morphine consumption and side effects during postoperative 24 hours. RESULTS: We found the DB group's VAS scores to be lower than the control group and block group's (p < 0.05) values at postoperative 1st, 2nd, 6th and 12th hours. VAS scores of group C were higher than of group B at postoperative first 2 hours. Time to first PCA demand was longer, morphine consumption values were lower and satisfaction scores were higher in group DB than in the other two groups (p < 0.05). CONCLUSIONS: Ilioinguinal-iliohypogastric nerve block with IV dexketoprofen increases patient satisfaction by decreasing opioid consumption, increasing patient satisfaction, which suggests that dexketoprofen trometamol is an effective non-steroidal anti-inflammatory analgesic in postoperative analgesia.

JUSTIFICATIVA Y OBJETIVO: El objetivo de este estudio fue evaluar los efectos de la aplicación intravenosa (IV) del dexketoprofeno trometamol en el bloqueo de los nervios ilioinguinal e Ilio-hipogástrico en la calidad analgésica y en el consumo de morfina después de la histerectomía abdominal total. MÉTODO: Estudio clínico controlado y aleatorio llevado a cabo con 61 pacientes. El estudio se hizo en un quirófano, en la sala de recuperación postanestésica y en el ambulatorio. Los 61 pacientes fueron aleatoriamente divididos en tres grupos: grupo control (Grupo C), grupo bloqueo (Grupo B) y grupo bloqueo con dexketoprofeno (Grupo BD). Antes de la incisión quirúrgica hecha después de la inducción de la anestesia, hicimos el bloqueo de los nervios ilioinguinal e ilio-hipogástrico (Grupo C recibió solución salina y grupos B y BD recibieron levobupivacaína). En contraste con los grupos C y B, el Grupo BD recibió dexketoprofeno. Administramos morfina a todos los pacientes para la analgesia con el uso del método ACP durante el postoperatorio de 24 horas. Registramos las puntuaciones EVA, los índices de satisfacción, el consumo de morfina y los efectos colaterales durante el postoperatorio de 24 horas. RESULTADOS: Los puntuaciones EVA del Grupo BD fueron menores que las de los grupos C y B en el postoperatorio (p < 0,05) en los intervalos de 1, 2, 6 y 12 horas. Las puntuaciones EVA del Grupo C fueron mayores que las del Grupo B en las primeras 2 horas del postoperatorio. El tiempo hasta la primera demanda de ACP fue más largo, los valores de consumo de morfina más bajos y los índices de satisfacción mayores en el Grupo BD que en los otros dos grupos (p < 0,05). CONCLUSIONES: El bloqueo de los nervios ilioinguinal e Ilio-hipogástrico con dexketoprofeno IV, aumenta la satisfacción del paciente y reduce el consumo de opioides, sugiriendo que el dexketoprofeno trometamol es un analgésico antiinflamatorio no esteroide eficaz en analgesia postoperatoria.

Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts / Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos

OBJECTIVE: A simple method to reduce the ischemia/reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. METHOD: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. RESULTS: Rat hearts with hyperosmotic perfusion showed higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, P<0.005), a lower reperfusion arrthythmia score (3.2 vs. 5.3, P<0.001), better ventricular function, and less creatine phosphokinase leakage (340.1 vs. 861.9, P<0.001) than normal osmotic controls. Myocardial catalase content and activity were increased significantly (1435 vs. 917 U/g wet weight, P<0.001) in hearts perfused with hyperosmotic solution in comparison to the normal osmotic controls. CONCLUSION: Pretreatment with hyperosmotic perfusion in normal rat hearts, which is attributed partly to the increased antioxidative activity, could provide beneficial effects from ischemia and reperfusion-induced injury by increasing coronary flow, and decreasing reperfusion arrhythmia.

OBJETIVO: Um método simples para reduzir a lesão de isquemia/reperfusão que pode acompanhar a cirurgia cardíaca teria grande valor clínico. O objetivo deste estudo foi investigar o efeito da perfusão hiperosmótica na isquemia/reperfusão em corações isolados de ratos perfundidos. MÉTODOS: Quarenta ratos machos Sprague-Dawley foram divididos aleatoriamente e tiveram os seus corações isolados perfundidos com tampão osmótico normal ou tampão hiperosmótico com a adição de glucose. Os corações foram então submetidos a 30 minutos de isquemia, seguida de 30 min de reperfusão. O fluxo coronariano, tempo de parada isquêmica, arritmia de reperfusão e da função ventricular foram registrados. Vazamento creatinofosfoquinase na artéria coronária, o miocárdio e atividade de superóxido dismutase e catalase foram também examinados. RESULTADOS: Crações de ratos com perfusão hiperosmótica apresentaram maior fluxo coronariano, tempo prolongado de parada isquêmica (10,60 vs. 5,63 min, P<0,005), menor pontuação de reperfusão arritmica (3,2 vs. 5,3, P<0,001), melhor função ventricular e menos vazamento de creatina fosfoquinase (340,1 vs. 861,9, P<0,001) do que controles normais osmóticos. Teor de catalase e atividade do miocárdio também tiveram aumento significativo (1435 vs. 917 peso U/g de peso fresco, P<0,001) em corações perfundidos com solução hiperosmótica em comparação com os controles normais osmóticos. CONCLUSÃO: O pré-tratamento com perfusão hiperosmótica em corações de ratos normais, o que é atribuído, em parte, ao aumento da atividade antioxidante, pode oferecer efeitos benéficos de isquemia e reperfusão induzida por lesão, aumentando o fluxo coronário e diminuindo a arritmia de reperfusão.

Comparative Analysis Between Thoracic Spinal Cord and Sacral Neuromodulation in a Rat Spinal Cord Injury Model: A Preliminary Report of a Rat Spinal Cord Stimulation Model

OBJECTIVE: The purpose of this study is to compare a neuroprotective effect of thoracic cord neuromodulation to that of sacral nerve neuromodulation in rat thoracic spinal cord injury (SCI) model. METHODS: Twenty female Sprague Dawley rats were randomly divided into 4 groups: the normal control group (n=5), SCI with sham stimulation group (SCI, n=5), SCI with electrical stimulation at thoracic spinal cord (SCI + TES, n=5), and SCI with electrical stimulation at sacral nerve (SCI + SES, n=5). Spinal cord was injured by an impactor which dropped from 25mm height. Electrical stimulation was performed by the following protocol: pulse duration, 0.1ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration at thoracic epidural space and S2 or 3 neural foramina for 4 weeks. Locomotor function, urodynamic study, muscle weights, and fiber cross sectional area (CSA) were investigated. RESULTS: All rats of the SCI + TES group expired within 3 days after the injury. The locomotor function of all survived rats improved over time but there was no significant difference between the SCI and the SCI + SES group. All rats experienced urinary retention after the injury and recovered self-voiding after 3-9 days. Voiding contraction interval was 25.5+/-7.5 minutes in the SCI group, 16.5+/-5.3 minutes in the SCI+SES group, and 12.5+/-4.2 minutes in the control group. The recovery of voiding contraction interval was significant in the SCI + SES group comparing to the SCI group (p<0.05). Muscle weight and CSA were slightly greater in the SCI + SES than in the SCI group, but the difference was not significant. CONCLUSION: We failed to establish a rat spinal cord stimulation model. However, sacral neuromodulation have a therapeutic potential to improve neurogenic bladder and muscle atrophy.

Comparative experimental study of myocardial protection with crystalloid solutions for heart transplantation / Estudo comparativo experimental da proteção miocárdica com soluções cristalóides para transplante cardíaco

BACKGROUND: There is a growing need to improve myocardial protection, which will lead to better performance of cardiac operations and reduce morbidity and mortality. Therefore, the objective of this study was to compare the efficacy of myocardial protection solution using both intracellular and extracellular crystalloid type regarding the performance of the electrical conduction system, left ventricular contractility and edema, after being subjected to ischemic arrest and reperfusion. METHODS: Hearts isolated from male Wistar (n=32) rats were prepared using Langendorff method and randomly divided equally into four groups according the cardioprotective solutions used Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1 (STH-1) and Celsior (CEL). After stabilization with KHB at 37ºC, baseline values (control) were collected for heart rate (HR), left ventricle systolic pressure (LVSP), maximum first derivate of rise left ventricular pressure (+dP/dt), maximum first derivate of fall left ventricular pressure (-dP/dt) and coronary flow (CF). The hearts were then perfused at 10ºC for 5 min and kept for 2 h in static ischemia at 20ºC in each cardioprotective solution. Data evaluation was done using analysis of variance in completely randomized One-Way ANOVA and Tukey's test for multiple comparisons. The level of statistical significance chosen was P<0.05. RESULTS: HR was restored with all the solutions used. The evaluation of left ventricular contractility (LVSP, +dP/ dt and -dP/dt) showed that treatment with CEL solution was better compared to other solutions. When analyzing the CF, the HTK solution showed better protection against edema. CONCLUSION: Despite the cardioprotective crystalloid solutions studied are not fully able to suppress the deleterious effects of ischemia and reperfusion in the rat heart, the CEL solution had significantly higher results followed by HTK>KHB>STH-1.

INTRODUÇÃO: Existe crescente necessidade de aprimorar a proteção miocárdica, para melhor desempenho das operações cardíacas e diminuição da morbimortalidade. Portanto, o objetivo deste estudo foi comparar a eficácia da proteção miocárdica usando tanto solução cristaloide tipo intracelular como extracelular quanto ao desempenho do sistema de condução elétrica, contratilidade do ventrículo esquerdo e edema, após parada isquêmica e posterior reperfusão. MÉTODOS: Corações isolados de ratos Wistar foram montados em Langendorff e aleatoriamente divididos em quatro grupos. de acordo com as soluções cardioprotetoras utilizadas Krebs-Henseleit-Buffer (KHB), Bretschneider-HTK (HTK), St. Thomas-1(STH-1) e Celsior (CEL). Após a estabilização com KHB a 37ºC, valores basais (controle) foram coletados para frequência cardíaca (FC), pressão sistólica do ventrículo esquerdo (PSVE), derivada máxima de aumento da pressão ventricular esquerda (+dP/dt), derivada máxima de queda da pressão ventricular esquerda (-dP/dt) e fluxo coronariano (FCo). Os corações foram então perfundidos a 10ºC por 5 min e mantidos por 2 h em isquemia estática a 20ºC em cada solução cardioprotetora. Avaliação dos dados foi por análise de variância inteiramente casualizados em One-Way ANOVA e teste de Tukey para comparações múltiplas. O nível de significância estatística escolhido foi P<0,05. RESULTADOS: Houve recuperação da FC com todas as soluções utilizadas. A avaliação da contratilidade ventricular esquerda (PSVE, +dP/dt e -dP/dt) demonstrou que o tratamento com a solução CEL foi melhor em comparação às outras soluções. Ao analisar o CF, a solução HTK indicou melhor proteção contra edema. CONCLUSÃO: Apesar das soluções cristaloides cardioprotetoras estudadas não serem capazes de suprimir os efeitos deletérios da isquemia e reperfusão no coração de ratos, a solução CEL apresentou resultado superior seguido por HTK>KHB>STH-1.

Transposable Elements: No More 'Junk DNA'

Since the advent of whole-genome sequencing, transposable elements (TEs), just thought to be 'junk' DNA, have been noticed because of their numerous copies in various eukaryotic genomes. Many studies about TEs have been conducted to discover their functions in their host genomes. Based on the results of those studies, it has been generally accepted that they have a function to cause genomic and genetic variations. However, their infinite functions are not fully elucidated. Through various mechanisms, including de novo TE insertions, TE insertion-mediated deletions, and recombination events, they manipulate their host genomes. In this review, we focus on Alu, L1, human endogenous retrovirus, and short interspersed element/variable number of tandem repeats/Alu (SVA) elements and discuss how they have affected primate genomes, especially the human and chimpanzee genomes, since their divergence.

Efecto del consumo de anticonceptivos orales en el flujo salival no estimulado, PH y capacidad buffer / Effect of oral contraceptive use in unstimulated salivary flow, pH and buffer capacity

La saliva, un elemento esencial en la preservación de salud oral, puede verse alterada por diversos factores, como el consumo de fármacos, en cuanto al flujo, pH o capacidad buffer, constituyendo un factor predisponente a diversas patologías (1). Comparar el flujo salival no estimulado, pH y capacidad buffer entre consumidoras y no consumidoras de anticonceptivos orales combinados. Cincuenta y seis mujeres sanas, entre 21 y 26 años de edad, con bajo riesgo cariogénico, dividida en dos grupos, consumidoras y no consumidoras de anticonceptivos orales. Para determinar el flujo salival no estimulado, se tomó una muestra de saliva durante 15 minutos. Para determinar los pH se utilizó un potenciómetro (PL-600Lab PH meter) y para determinar capacidad buffer se utilizó el método de Ericsson. Para analizar la significancia estadística de las diferentes pruebas se realizó la prueba U Mann-Whitney utilizando el software SPSS versión 14.0. El promedio de flujo salival no estimulado observado en este estudio, es mayor entre consumidoras de anticonceptivos orales, con un p<0.005. En cuanto a capacidad buffer, se obtuvieron valores levemente superiores en el grupo consumidor, mientras que los valores de pH resultaron similares entre ambos grupos. El flujo salival no estimulado se ve aumentado en las consumidoras de anticonceptivos orales combinados, mientras que la capacidad buffer presenta un incremento no significativo, mientras que el pH salival arroja valores similares para ambos grupos

Saliva is an essential element in oral health preservation and its pH, buffer capacity and flow rate, have a fundamental role. These factors may be altered by, among others, drug consumption which predisposes to several diseases (1). To compare the non-stimulated salivary flow rate, pH and buffer capacity between patients under Oral contraceptives medication and not taking any medication. Fifty six healthy women, aged 21 to 26 years, with low cariogenic risk, divided into two groups: under oral contraceptives medication and without medication. To determine the non-stimulated salivary flow rate, was taken a saliva sample during 15 minutes. To determine the pH, was used a potentiometer (PL 600Lab PH-meter) and buffer capacity was measured by Ericsson's method. Mann-Whitney test was performed using SPSS software version 14.0 to determine statistical significance. Mean of stimulated salivary flow rate is not statistically significantly in subjects under oral contraceptives medication (p <0.005). Buffer capacity showed slightly higher values in study group, while the pH values were similar in study and control groups. The stimulated salivary flow rate is not increased by consuming the Oral contracetives, the salivary pH shown similar values for both groups, and finally, the salivary buffer capacity, shown increased in the consumer group, however, it does not statistically significant

Estudo comparativo da eficiência da eletroforese alcalina em acetato de celulose na identificação de hemoglobinas utilizando diferentes tampões / Comparative study of the alkaline electrophoresis on cellulose acetate efficiency to identify hemoglobins by using different buffers

As hemoglobinas podem apresentar alterações moleculares denominadas hemoglobinopatias caracterizadas pela ineficiência da produção das cadeias de globinas (alfa ou beta) ou por alterações estruturais na síntese destas cadeias. Tais alterações estruturais promovem a formação de hemoglobinas variantes (anômalas) e o desbalanceamento na síntese destas cadeias tem como consequência a talassemia. O diagnóstico das hemoglobinopatias é realizado essencialmente por avaliação eletroforética. Este trabalho teve como objetivo avaliar a influência de diferentes tampões de eletroforese na caracterização de hemoglobinas variantes por meio de técnica de eletroforese alcalina em acetato de celulose. Considerando as características de separação e nitidez das bandas obtidas concluímos que o tampão TEB (Tris base 0,090 M, Ácido bórico 0,090 M, EDTA0,002 M, pH 8,2) na concentração de 0,5X foi o mais eficiente na caracterização das hemoglobinas testadas. Este tampão além de permitir uma melhor separação eletroforética entre as diferentes hemoglobinas, também permitiu uma maior estabilidade da hemoglobina H, favorecendo a identificação mais eficaz dessa hemoglobina instável.

Effect of propofol on cardiac function and gene expression after ischemic-reperfusion in isolated rat heart / 대한마취과학회지

BACKGROUND: The aim of this study was to examine the cardiac function and transcriptional response of the heart to propofol after ischemia-reperfusion. METHODS: Rat hearts were Langendorff-perfused using the modified Krebs-Henseleit buffer, and took 20 min stabilizing periods, 40 min ischemia periods, and then 120 min reperfusion period. The hearts were divided into 5 groups; Control: 180 min perfusion after stabilization, Ischemic: 40 min global ischemia after stabilization, followed by 120 min reperfusion, Pre: 2 micrometer propofol treatment was preformed only before ischemia, Post: 2 micrometer propofol treatment was performed only during reperfusion after ischemia, Pre/Post: 2 micrometer propofol treatment was performed both before and after ischemia. The measurement for cardiac performances, such as left ventricular developed pressure (LVDP), rate of left ventricular pressure generation (dP/dt), heart rate, and coronary flow were obtained. The expression profiles of isolated mRNA were determined by using Agilent microarray and real time-polymerase chain reaction (RT-PCR) was used to confirm the microarray results for a subset of genes. RESULTS: The Post group showed better LVDP and dP/dt than the Ischemic group. But there were no significant differences in heart rate and coronary flow among the groups. On the results of RT-PCR, the expressions of Abcc9, Bard1, and Casp4 were increased, but the expressions of Lyz, Casp8, and Timp1 were decreased in the Post group compared with the Ischemic group. CONCLUSIONS: This study suggests that 2 micrometer propofol may provide cardioprotective effect, and modulate gene expression such as apoptosis, and K(ATP) ion channel related-genes during reperfusion in the isolated rat hearts.

Effect of propofol on cardiac function and gene expression after ischemic-reperfusion in isolated rat heart / 대한마취과학회지

BACKGROUND: The aim of this study was to examine the cardiac function and transcriptional response of the heart to propofol after ischemia-reperfusion. METHODS: Rat hearts were Langendorff-perfused using the modified Krebs-Henseleit buffer, and took 20 min stabilizing periods, 40 min ischemia periods, and then 120 min reperfusion period. The hearts were divided into 5 groups; Control: 180 min perfusion after stabilization, Ischemic: 40 min global ischemia after stabilization, followed by 120 min reperfusion, Pre: 2 micrometer propofol treatment was preformed only before ischemia, Post: 2 micrometer propofol treatment was performed only during reperfusion after ischemia, Pre/Post: 2 micrometer propofol treatment was performed both before and after ischemia. The measurement for cardiac performances, such as left ventricular developed pressure (LVDP), rate of left ventricular pressure generation (dP/dt), heart rate, and coronary flow were obtained. The expression profiles of isolated mRNA were determined by using Agilent microarray and real time-polymerase chain reaction (RT-PCR) was used to confirm the microarray results for a subset of genes. RESULTS: The Post group showed better LVDP and dP/dt than the Ischemic group. But there were no significant differences in heart rate and coronary flow among the groups. On the results of RT-PCR, the expressions of Abcc9, Bard1, and Casp4 were increased, but the expressions of Lyz, Casp8, and Timp1 were decreased in the Post group compared with the Ischemic group. CONCLUSIONS: This study suggests that 2 micrometer propofol may provide cardioprotective effect, and modulate gene expression such as apoptosis, and K(ATP) ion channel related-genes during reperfusion in the isolated rat hearts.

Palliative treatment of intractable hematuria in context of advanced bladder cancer a systematic review

In a patient with bladder urothelial cancer that is not suitable for or does not choose curative treatment, intractable hematuria is a disastrous condition. In this article, we tried to review the literature and extract a stepwise approach for palliative treatment of hematuria in these patients. The MEDLINE was searched with the help of the Medical Subject Headings system using different combinations of terms urinary bladder neoplasm, hematuria, carboprost, cyclophosphamide, cystitis, alum, and hyperbaric oxygenation. The articles were separately reviewed by the two authors and verified by each other. Eventually, a decision tree was developed for management of gross hematuria in patients with bladder cancer. Although, there was not any reported randomized controlled trial or prospectively designed study, the available case series were rather expressive to draw out a logical approach. Formalin has a grave adverse effect profile and is recommended only in special circumstances. For management of each case of gross hematuria in bladder cancer, the etiology of bleeding is the most important determinant. Hematuria in the context of advanced bladder neoplasms can now be effectively treated with fewer side effects using all available modalities in a logical holistic approach. We proposed a decision tree for management of hematuria in this context. However, regarding lack of well-designed trials, a treatment method should be based on individualized scenarios and clinical experience, bringing into account the patient's preferences

Dexketoprofen trometamol in the treatment of chronic prostatitis/chronic pelvic pain syndrome / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of dexketoprofen trometamol in the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).</p><p><b>METHODS</b>A total of 115 patients with CP/CPPS were divided into a dexketoprofen trometamol group (n = 40), treated with dexketoprofen trometamol (25 mg, tid) and terazosin (2 mg, qn), an indometacin group (n = 40) given indometacin (25 mg, tid) and terazosin (2 mg, qn), and a terazosin group (n = 35) administered terazosin (2 mg, qn) only, all treated for 4 weeks. Scores on the NIH-chronic prostatitis symptom index (NIH-CPSI) were obtained before and after the treatment, and the efficacy and adverse events were observed and compared.</p><p><b>RESULTS</b>The NIH-CPSI scores were significantly improved after the treatment in all the three groups. The clinical efficacy was significantly better in the dexketoprofen trometamol and indometacin groups than in the terazosin group (P < 0.05), but with no significant difference between the former two (P > 0.05). The rates of adverse events were 10.00%, 18.57% and 27.50% in the dexketoprofen trometamol, terazosin and indometacin groups, significantly lower in the former two than in the latter one (P < 0.05).</p><p><b>CONCLUSION</b>The combination of dexketoprofen trometamol with terazosin could effectively improve the clinical symptoms of CP/CPPS, better than terazosin in therapeutic efficacy and than indometacin in drug tolerance.</p>