Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Sexualidad y climaterio: una mirada integral / Sexuality and climacteric: a comprehensive approach

Cuando hablamos de sexualidad humana debemos saber que estamos hablando de una compleja y cambiante interacción de factores biológicos y socioemocionales altamente influenciables por la familia, la religión y los patrones culturales. Esto se ve en los hombres y en las mujeres, especialmente en las mujeres. La sexualidad es un concepto intuitivo que cuesta definir. Según la Organización Mundial de la Salud, se define salud sexual como "un estado de bienestar físico, emocional, mental y social relacionado con la sexualidad, la cual no es solamente la ausencia de enfermedad, disfunción o incapacidad". Es una definición que tiene en cuenta varios conceptos, muy importantes todos ellos. La respuesta sexual consiste en una serie de cambios neurofisiológicos, hemodinámicos y hormonales que involucran al conjunto del organismo. Si bien es similar en ambos sexos, en las mujeres no siempre el inicio y la progresión se correlacionan en forma sistemática o lineal como en los hombres. Y de ese intrigante devenir de la respuesta sexual femenina surge la dificultad del diagnóstico de la "disfunción sexual femenina". Podríamos resumirla en "un conjunto de trastornos en los que los problemas fisiológicos o psicológicos dificultan la participación o la satisfacción en las actividades sexuales; lo cual se traduce en la incapacidad de una persona para participar en una relación sexual de la forma que le gustaría hacerlo"16. La menopausia es percibida por muchas mujeres como el fin de la sexualidad, y no solo como el fin de la vida reproductiva. Si bien es cierto que en esta etapa la actividad sexual suele declinar y puede verse afectada por una serie de factores hormonales, psicológicos y socioculturales, para la mayoría de las mujeres la sexualidad sigue siendo importante. Debemos comprender que la disfunción sexual femenina, en cualquier etapa de la vida, es multicausal y multidimensional. A la hora de realizar el abordaje de una paciente, debemos tener en cuenta todos los factores involucrados y saber con qué herramientas contamos. El abordaje terapéutico clásicamente incluye la terapia psicológica y la terapia hormonal. Sin embargo, recientemente se ha incorporado una nueva droga recientemente aprobada por la FDA de los Estados Unidos para el tratamiento del deseo sexual hipoactivo en la mujer: el flibanserín, un psicofármaco que actúa a nivel de mediadores del deseo sexual en el sistema nervioso central, favoreciéndolo. (AU)

When we talk about human sexuality, we know that we are talking about a complex and changing interaction between biological and socioemotional factors, which are highly influenced by society, family, religion and cultural norms. This can be seen in men and women especially in women. Sexuality is an intuitive concept difficult to define. According to the World Health Organization, it is defined as "A state of physical, emotional, mental and social well being related to sexuality, which is not merely the absence of disease, dysfunction or disabilityˮ. It is a definition that takes into account several concepts, all very important. Sexual response is a series of neurophysiological, hemodynamic and hormonal changes involving the whole body. While similar in both sexes, women are not always the onset and progression correlate systematically or linearly as in men. And that intriguing evolution of the female sexual response, the difficulty of diagnosis of "female sexual dysfunctionˮ. We could summarize it in "a group of disorders in which the physiological or psychological problems impede participation or satisfaction in sexual activities; which results in the inability of a person to participate in a sexual relationship the way she or he would like to do itˮ16. Menopause is perceived by many women as to the end of sexuality, not only as the end of reproductive life. Sexual activity declines with age, and may be affected by a number of hormonal, psychological and sociocultural factors, but, for most women it continues to be important. We must understand that female sexual dysfunction, at any stage of life is multicausal and multidimensional. When approaching a patient, it is important to know all the factors that are involved, and which tools we have for deal with it. Classically, the therapeutic approach has consisted of psychological therapy and hormone therapy. However, we have to consider a recently approved drug by the FDA for the treatment of hypoactive sexual desire in women: Flibanserin. It is a psychotropic substance that acts on the mediators of sexual desire on the central nervous system favoring it. (AU)

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children

The therapeutic scheme of triclabendazole (TCBZ), the recommended anthelmintic against Fasciola hepatica , involves 10mg/kg of body weight administered in a single dose; however, clinical trials in children are scarce. We evaluated the efficacy and tolerability of 2 schemes of TCBZ.

Fascioliasis hepática humana: resistencia al tratamiento con triclabendazol / Resistant human fasciolasis: Report of four patients

Human fascioliasis is a parasitic zoonosis that affects the liver of human and herbivorous animals. In chronic cases, its diagnosis is confirmed by direct visualization of parasitic eggs in stool examination, by positive testing for Fasciola hepatica antigens in stools, or by direct observation of parasites by endoscopic retrograde cholangiography or surgery. In acute cases, serological reactions as immunoblothing or detection of parasite antigens in the blood are useful. The treatment of choice is triclabendazole. However, parasite resistance in animals, as well as in man, has been reported to this drug. We report four patients in whom the parasitic infection persisted despite a course of treatment with triclabendazole.

PONV in ambulatory surgery: a comparison between ramosetron and ondansetron: a prospective, double-blinded, and randomized controlled study

Postoperative nausea and vomiting [PONV] frequently hampers implementation of ambulatory surgery in spite of so many antiemetic drugs and regimens. the study was carried out to compare the efficacy of Ramosetron and Ondansetron in preventing PONV after ambulatory surgery. It was a prospective, double blinded, and randomized controlled study. 124 adult patients of either sex, aged 25-55, of ASA physical status I and II, scheduled for day care surgery, were randomly allocated into Group A [[n=62] receiving [IV] Ondansetron [4 mg]] and Group B [[n=62] receiving IV Ramosetron [0.3 mg]] prior to the induction of general anesthesia in a double-blind manner. Episodes of PONV were noted at 0.5, 1, 2, 4 h, 6, 12, and 18 h postoperatively. Statistically significant difference between Groups A and B [P <0.05] was found showing that Ramosetron was superior to Ondansetron as antiemetic both regarding frequency and severity. it was evident that preoperative prophylactic administration of single dose IV Ramosetron [0.3 mg] has better efficacy than single dose IV Ondansetron [4 mg] in reducing the episodes of PONV over 18 h postoperatively in patients undergoing day-care surgery under general anesthesia

randomized clinical trial comparing the efficacy and safety of ramosetron versus ondansetron in patients undergoing abdominal surgery under general anesthesia

Post-operative nausea and vomiting is one of the most common and distressing complications after anesthesia and surgery. It may lead to serious post-operative complications. Ramosetron is a newer 5-HT3 receptor antagonist and has more potent and longer duration of antiemetic effects compared to first generation 5HT3 receptor antagonists. The purpose of this study was to compare the efficacy of Ramosetron for the prevention of post-operative nausea and vomiting with that of Ondansetron in patients undergoing abdominal surgeries under general anesthesia. In this randomized, double-blind study, 60 patients, 18-60 years of both genders falling under ASA I-II category scheduled for abdominal surgery were included. Group I received I.V ramosetron 0.3 mg while group II received I.V Ondansetron 4 mg at the time of extubation. The standard general anesthetic technique was used throughout. Postoperatively the incidences of nausea, vomiting, and safety assessments were performed at 1, 2, 6, and 24 h during the first 24 h after surgery. There were no differences between groups with respect to patient demographics. The percentage of patients who had complete response [no PONV, and no need for another rescue antiemetic] from 0 to 24 h after anesthesia was 56% with ramosetron and 33% with ondansetron. The corresponding rates at 1, 2, 6, and 24 h after anesthesia were 76% and 63%, 76% and 50%, 100 and 83%, 100 and 93%, respectively. Safety profiles of the two drugs were comparable, as no clinically serious adverse effects caused by study drugs were observed in either of the groups. Our study concludes that prophylactic therapy with ramosetron is highly efficacious than ondansetron in preventing PONV in patients undergoing abdominal surgery under general anesthesia

New orally active anticoagulants in critical care and anesthesia practice: The good, the bad and the ugly.

With the adoption of dabigatran, rivaroxaban, and apixaban into clinical practice, a new era has arrived in the practice of oral anticoagulants. Venous thromboembolism (VTE) has traditionally been underdiagnosed and under treated in Asia. With increasing longevity, the diagnosis and the need for management of atrial fibrillation (AF) and VTE is likely to increase significantly. The new orally active anticoagulants (NOACs) have reasonably filled the lacunae that clinicians traditionally faced when treating patients with vitamin K antagonist (VKA). Unlike VKA, NOACs do not need frequent monitoring. Therefore, more patients are likely to get therapeutic effects of anticoagulation and thus reduce morbidity and mortality associated with VTE and AF. However, the clinicians need to be circumspect and exercise caution in use of these medications. In particular (in geriatric population), the clinicians should look out for drug-drug interactions and underlying renal insufficiency. This would ensure therapeutic efficacy and minimize bleeding complications. Here, it is important to note that the antidote for NOACs is not available and is a major concern if emergency surgical procedure is required in their presence.

Nuevos anticoagulantes orales en la prevención del ataque cerebrovascular / New oral anticoagulants in stroke prevention

Introduction: Atrial fibrillation (AF) is the most common arrhythmia. AF increases stroke risk by 5-fold and accounts for 15 percent of stroke. For more than 50 years, vitamin K antagonists were the only available oral anticoagulation. The two major classes of novel oral agents are direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (apixaban or rivaroxaban). These new agents require no routine laboratory monitoring and they are administered in a fixed dose. Method: A non systematic literature review was performed. Results: We performed a critical review of articles about new oral anticoagulants in stroke prevention. We evaluated properties of these agents and we compare efficacy and safety outcomes shown in clinical trials about new oral anticoagulants in AF. Discussion: New oral anticoagulants are at least as good as warfarin at preventing stroke in patients with AF. They seem to be safer than warfarin with significantly less intracranial bleeding. Trials demonstrate dabigatran to be the most effective in decreasing ischemic strokes, apixaban superior to warfarin with statistically lower mortality, and rivaroxaban no worse than warfarin for those with higher stroke risk. Conclussion: New oral anticoagulants have several advantages in comparison with warfarin, but we need further trials to know better the efficacy and safety of these new agents.

Introducción: La fibrilación auricular (FA) es la arritmia más frecuente, se asocia a un riesgo 5 veces mayor de ataque cerebrovascular (ACV), y da cuenta del 15 por ciento de los ACV isquémicos. Por más de medio siglo el tratamiento anticoagulante oral en FA ha estado limitado al uso de antagonistas de la vitamina K. Los nuevos anticoagulantes orales, se clasifican en dos categorías principales: inhibidores de la trombina como el dabigatrán y los inhibidores del factor Xa, como el apixabán y el rivaroxabán. Estos fármacos no requieren monitorización de los niveles de anticoagulación y se administran en dosis fija. Método: Revisión no sistemática de la literatura. Resultados: Se analizan de manera crítica los artículos sobre nuevos anticoagulantes orales en la prevención de ACV. Se evalúan las propiedades de estos nuevos agentes y se comparan los desenlaces de eficacia y de seguridad de los ensayos clínicos de los estos fármacos. Discusión: Los nuevos anticoagulantes orales son al menos tan efectivos que la warfarina en la prevención de ACV cardioembólico en pacientes con FA. Parecen ser más seguros con menor frecuencia de hemorragia intracranial. El dabigatrán es el más efectivo en disminuir el ACV isquémico, el apixabán es superior a la warfarina con una mortalidad significativamente inferior, y el rivaroxabán es no inferior a warfarina para pacientes con alto riesgo de ACV. Conclusión: Los nuevos anticoagulantes orales ofrecen varias ventajas en comparación a warfarina, sin embargo, se requiere se estudios adicionales para conocer más detalladamente su efectividad y perfil de seguridad.

Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Evaluation of two doses of triclabendazole in treatment of patients with combined schistosomiasis and fascioliasis

To determine the safety and efficacy of 2 consecutive doses of triclabendazole [TCBZ] in the treatment of Schistosoma mansoni infection in human cases infected with both S. mansoni and Fasdola spv we conducted afield survey involving 6314 individuals from 15 villages. The overall prevalence of schistosomiasis alone was 15.8%, of fascioliasis alone 2.2%, and of combined infection 0.7%. Treatment with 2 doses of TCBZ was given to the 49 cases with combined infection. Eight weeks after treatment, the cure rate was 96% for fascioliasis and was 32.7% for schistosorniasis. All schistosomiasis cases cured had a low intensity infection. Liver function tests done before I treatment and 8 weeks after substantiate the safety of 2 doses of TCBZ given to those with combined infection. Administration of TCBZ should precede praziquantel in treatment of combined infection, however TCBZ cannot be recommended for infection with S. mansoni alone

A Case of Biliary Fascioliasis by Fasciola gigantica in Turkey

A case of Fasciola gigantica-induced biliary obstruction and cholestasis is reported in Turkey. The patient was a 37- year-old woman, and suffered from icterus, ascites, and pain in her right upper abdominal region. A total of 7 living adult flukes were recovered during endoscopic retrograde cholangiopancreatography (ERCP). A single dose of triclabendazole was administered to treat possible remaining worms. She was living in a village of southeast of Anatolia region and had sheeps and cows. She had the history of eating lettuce, mallow, dill, and parsley without washing. This is the first case of fascioliasis which was treated via endoscopic biliary extraction during ERCP in Turkey.

Efectividad del uso combinado de un inhibidor de Rho Kinasa y de un antagonista del receptor de angiotensina II en la prevención de hipertrofia ventricular en ratas hipertensas / Effectiveness of the combined use of a Rho-kinase inhibitor and an Angiotensin II receptor antagonist in the prevention of left ventricular hypertrophy in hypertensive rats

La actividad de Rho kinasa (ROCK) cardíaca en la hipertensión arterial (HTA) y el efecto del tratamiento antihipertensivo conjunto han sido poco estudiados. Hemos planteado que la adición de un inhibidor de ROCK al tratamiento antihipertensivo convencional podría tener efectos preventivos adicionales al uso aislado del antihipertensivo. Objetivo: Determinar la actividad de ROCK ventricular y parámetros de remodelamiento cardíaco en ratas hipertensas con y sin tratamiento antihipertensivo, adicionando un inhibidor directo de ROCK. Métodos. Se usaron ratas Sprague Dawley de 150 grs. ( n = 12 - 13/grupo) unifrectomizadas tratadas con desoxicorticosterona (DOCA, 100 mg/Kg/sem sbc) durante 6 semanas. Como controles se usaron ratas unifrectomizadas. Otros 3 grupos recibieron DOCA y además el antagonista del receptor de angiotensina n, candesartán (10 mg/kg/día) o el inhibidor de la vía ROCK fasudil (50 mg/Kg/dia), o la combinación de ambos (5 y 25 mg/Kg/dia, respectivamente), vía gavage desde la tercera semana post cirugía, durante 3 semanas. Al finalizar los tratamientos se determinó la masa corporal (MC), presión arterial sistólica (PAS) y la masa cardíaca relativa (MCR). Además se midió en el ventrículo izquierdo la fosforilación de la fosfatasa de la miosina (MYPT-1) como índice de activación de ROCK, la infiltración de macrófagos/ monocitos (células ED1 positivas), la expresión proteica de colágeno I (por Western blot) y la expresión génica de la subunidad gp91 de NADPH oxidasa y eNOS por RTPCR. Resultados: Con respecto de las ratas sham, en las ratas hipertensas se observó hipertrofia cardiaca de 63 por ciento (p < 0,05), junto a aumento significativo (p < 0,05) de MYPT-1 fosforilado/total (300 por ciento), de colágeno miocárdico I (en 14 veces), de células ED1 en 270 por ciento y de la expresión génica de la subunidad gp91 de NADPH...

Background: The effect of cardiac Rho-kinase (ROCK) on hypertension (HT) and cardiac hypertrophy prevention and also the combined anti-hypertensive treatment have been scarcely studied. We hypothesized that the addition of a ROCK inhibitor to conventional anti-hypertensive treatment may have additional beneficial effects. Ainv to determine ventricular ROCK activity and ventricular remodeling in hypertensive rats treated with Angiotensin II inhibition with the addition of a ROCK inhibitor. Methods: Sprague-Dawley rats weighing 150 grams had one kidney removed and received deoxycortisterone acétate (DOCA, 100 mg/kg/week, during 6 weeks). Unilaterally nephrectomized rats were used as controls. The other 3 groups received DOCA along with the Angiotensin II receptor blocker candesartan (10 mg/kg/day) or the combination of both agents (5 and 25 mg/kg/day, respectively) and ROCK inhibitor fasudil (50 mg/kg/day) for 3 weeks starting 3 weeks after surgery. Body mass (BM), systolic blood pressure (SBP) and relative cardiac mass (RCM) were measured. In addition, myosin phosphatase (MYPT-1) phosphorylation was measured as an indicator of ROCK activation. Cardiac infiltration of macrophages/monocytes (ED1 positive cells), collagen I protein contení (by Western Blot) and also cardiac gene expression of NADPH oxydase GP91 subunit and eNOS were determined by RT-PCR. Results: In hypertensive rats we observed cardiac hypertrophy by 63 percent (p < 0.05), a 300 percent increase in cardiac MYPT-1 phosphorylation (p< 0.05), 14 times increase in myocardial collagen type 1,270 percent increase in ED1 cells, a 75 percent increased gene expression of NADPH oxydase GP91 subunit and a 37 percent reduction (p< 0.05) in the gene expression of cardiac eNOS. In hypertensive DOCA rats treated during 3 week with candesartan, fasudil or the combination of both, we observed a significant reduction in cardiac hypertrophy and normalization of SBP, MYPT-1 phosphorylation, ...

La sobrexpresión génica vascular de NADPH oxidasa en la hipertensión arterial experimental se reduce solamente con inhibición directa de Rho kinasa / Vascular gene overexpression of NADPH oxydase in experimental hypertension is only reduced by direct Rho kinase inhibition

Uno de los objetivos del tratamiento antihipertensivo, más allá de normalizar las cifras tensionales, es disminuir/regresar el remodelado patológico hipertensivo cardiovascular y renal, de manera de reducir eficientemente el riesgo dado por esta patología. Al respecto, la vía de señalización intracelular de la Rho kinasa (ROCK) es un mecanismo de vasoconstricción y de promoción de remodelado que podría ser un blanco atractivo en el tratamiento antihipertensivo. Objetivo: Evaluar a nivel vascular los niveles de TGF beta, la expresión génica vascular de NADPH oxidasa (fuente de stress oxidativo vascular), y el grado de inflamación parietal y su dependencia de ROCK en la hipertensión arterial (HTA) experimental. Métodos: Se compararon 5 grupos experimentales. Se usó el modelo de HTA por administración de deoxicorticosterona (DOCA, 100mg/Kg, sc una vez/semana) + sal en ratas Sprague Dawley uninefrectomizadas. Como controles, se usaron ratas uninefrectomizadas (Sham). Las ratas DOCA se randomizaron para recibir el inhibidor específico de ROCK fasudil (Fas, 50 mg/kg/d, por gavage, durante 3 semanas), desde la semana 3 post cirugía, o candesartán (Cand, 10 mg/kg/d, por gavage, durante 3 semanas), o fasudil (25 mg/kg/d) + candesartan (5 mg/ kg/d por gavage, 3 semanas ). Al finalizar los experimentos se midieron en la aorta los niveles de MYPT1 fosforilada/total, blanco de ROCK y estimador de su activación (por Western blot), de TGF beta (por Western blot), los niveles de mRNA de las subunidades p22 Phox y gp 91 de la NADPH oxidasa (por RT PCR) y el número de células infamatorias ED1 en anillos aórticos (por inmunohistoquímica). Resultados: La presión arterial sistólica aumentó en las ratas DOCA a 172 +/- 7 mm Hg (p < 0,05) y fue normalizada después de 3 semanas de tratamiento con candesartán, fasudil y de candesartán + fasudil. La actividad de ROCK en aorta aumentó en 4 veces en las ratas hipertensas (p < 0,05)...

Background: Rho kinase (ROCK) activity promotes vasoconstriction and pathological vascular remodeling in experimental hypertension. Our working hypothesis is that ROCK inhibition could be an attractive target to prevent vascular remodeling in hypertension. Objectives: We evaluated vascular TGF beta, the genic expression of NADPH oxydase (a vascular oxidative stress source) and its dependency from ROCK activation in experimental hypertension in the rat. Methods: Five experimental groups were compared. Hypertension was induced by the administration of salt and deoxycorticosterone acetate (DOCA, 100 mg/Kg, weekly) to unilaterally nephrectomized rats. Unilaterally nephrectomized rats were used as controls (controls). DOCA rats were randomized to receive either Fasudil (a ROCK inhibitor, 50 mg/Kg/day) or candesartan (CAND, 10 mg/Kg/day for 3 weeks), starting 3 weeks after surgery. The other group received fasudil (25 mg/Kg/day) plus CAND (5 mg/Kg/day) for 3 weeks. After treatment, phosphorilated MYPT1 (a ROCK target expressing ROCK activation) was measured in aortic wall rings by Western Blot. We also determined TGF-beta (Western Blot), p22 Phox and gp 91subnits of NADPH oxydase mRNA (RT-PCR) and the number of ED1 infammatory cells. Results: In DOCA rats, SBP increased to 172 +/- 7 mm Hg (p < 0,05), and returned to normal values after 3 weeks with candesartan, fasudil or both combined. In these rats, ROCK activity in aorta was increased 4 times (p < 0,05) and returned to control values in the 3 groups receiving treatment. p22 Phox and gp 91subnits of NADPH oxydase mRNA were increased by 80 and 90 percent, respectively (p<0,05). These changes were reduced to control values in rats receiving fasudil and candesartan + fasudil. Gene expression of TGF-beta increased 4 times, and the number of ED1...

Comparison of ramosetron and ondansetron for control of post-operative nausea and vomiting following laparoscopic cholecystectomy.

Background: Post-operative nausea and vomiting (PONV) is common. 5HT 3 receptor antagonists are commonly used drugs for its prevention. A study was designed to compare the efficacy and safety of ramosetron and ondansetron in patients undergoing laparoscopic cholecystectomy (lap chole). Materials and Methods: A prospective randomized case controlled study was conducted at J. N. Medical College Hospital, Aligarh Muslim University, Aligarh, India, in patients who underwent lap chole following intravenous administration of ondansetron (4mg) or ramosetron (0.3mg) at the end of surgery, and efficacy as well as side effects of ondansetron and ramosetron was documented and compared. Results: One hundred and thirty adult females undergoing lap chole were studied - 65 patients in each of the two groups. In first 24 h after surgery, complete response (No PONV) was observed in 28 patients of the ondansetron group and in 32 patients of the ramosetron group (P>0.05). Complete response in the second 24 h after surgery was observed in 30 patients of the ondansetron group and in 45 patients of the ramosetron group (P<0.05). During the first and second 24 h, PONV requiring rescue antiemetic was significantly higher (P<0.05) in the ondansetron group as compared to the ramosetron group. Adverse drug effects in the post-operative period were observed in 11 and 8 patients in ondansetron and ramosetron groups respectively (P>0.05). Conclusion: Ramosetron was found safe and more effective antiemetic than ondansetron in patients undergoing lap chole.

Evaluation of fixed dose combination (FDC) of telmisartan+ramipril usage in patients with micro-albuminuria and persistent hypertension: A TRIUMPH study.

Micro-albuminuria is a marker for declining kidney function and predicts increasing cardiovascular risk especially in diabetic hypertensives. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors may slow the progression of proteinuric kidney disease and thus would be valuable in these high risk patients. The present study was undertaken to assess the efficacy and tolerability of a fixed dose combination (FDC) of telmisartan and ramipril in adult Indian patients with sustained stage 2 hypertension, comorbidities and micro-albuminuria. A total 382 patients were enrolled in this multicentric, prospective open, non-comparative phase IV postmarketing surveillance study by 40 physicians in India and treated with FDC of telmisartan 40 mg+ ramipril 5 mg once daily for 12 weeks. A total 370 patients completed the study but 12 patients were lost to follow-up and considered as drop-outs. There was a significant (p<0.05) reduction in the systolic blood pressure (SBP) from 170.89 at baseline to 132. 77 mm Hg at week 12 and diastolic blood pressure (DBP) from 104.47 to 83.30 mm Hg at the end of 12 weeks therapy as well as urine albumin levels from 186.25 mg/24-hour to 62.42 mg/24-hour (66.49%) at the end of 12 weeks. Overall assessment of treatment was rated as good to excellent in 87.3% and fair in 11.4% patients. The most common adverse event reported was cough (5.2%). Results of the present study indicate that the FDC of telmisartan+ramipril brings about significant reductions in the systolic and diastolic blood pressure as well as urine albumin excretion.

Phase II trial of ramosetron plus dexamethasone in the prevention of cisplatin-induced nausea and vomiting.

OBJECTIVE: To evaluate the clinical efficacy of ramosetron hydrochloride in the combination with dexamethasone for the prevention of nausea and vomiting induced by cisplatin. MATERIAL AND METHOD: Thirty in-patients with malignant tumor being treated with cisplatin at a dose of 70 mg/m2 or more for a total of 94 cycles were scheduled to receive ramosetron 0. 3 mg IV given 30 minutes before chemotherapy and dexamthasone 20 mg IV on day 1 for the prevention of acute emesis and continued with ramosetron tablet 0.1 mg one tablet orally one hour before chemotherapy or in the morning in case of no chemotherapy scheduled and dexamethasone capsule 5 mg 2 capsules twice daily on day 2 to day 5 for the prevention of delayed emesis. The evaluation period started concomitantly with the start of chemotherapy (hour 0) and continued until 24 hours after completion of chemotherapy. The antiemetic efficacy of ramosetron plus dexamethasone was analyzed according to the occurrence of nausea and vomiting within 24 hours of treatment cycle. The study emphasized both on acute and delayed emesis control. ASSESSMENT: The degree of severity of nausea was determined according to the following criteria: 0: None: nausea does not occur, 1: Mild: slight nausea but no disruption to daily acitivites, 2: Moderate: nausea and some disruption to daily activities, 3: Severe: extreme nausea and severe disruption to daily activities. The control of vomiting episodes was determined according to the frequency of vomiting (including retching) as the following criteria: Complete: 0 emesis episode, Major: 1-2 emesis episodes, Minor: 3-5 emesis episodes, Failure: > 5 emesis episodes. RESULTS: The result of all 94 cycles of the first day of treatment on acute emesis (0-24 hours) were none 80.9%, mild 18.1%, and moderate 1.1% for nausea episode. For the vomiting control were complete 81.9%, major 16%, minor 1.1% and failure 1.1% respectively. The efficacy of the prevention of delayed emesis (day 2 to day 5) for nausea episode were 67%, 66%, 70.2%, and 75.5% no nausea respectively. For the vomiting control were 75.5%, 74.5%, 86.2%, and 88.3% complete control on day 2 to day 5. No serious adverse events occurred. Hiccups, constipation, and dull headache were reported as the common side effects of ramosetron. CONCLUSION: Ramosetron combined with dexamethasone is effective for the prevention of both acute and delayed emesis associated with cisplatin. The prevention of acute emesis seems to be more effective than the prevention of delayed emesis. Adverse events were mild. No serious side effects occurred in the present study.

Assessment of efficacy, safety and tolerability of fixed dose combination of telmisartan 40mg and hydrochlorothiazide 12.5mg in adult Indian patients with mild to moderate hypertension.

The objective of the study was to assess the efficacy, safety and tolerability of a fixed dose combination of telmisartan 40 mg and hydrochlorothiazide 12.5 mg in adult Indian patients with mild to moderate hypertension. A prospective, multicentric, open-label, non-comparative, phase IV study was conducted. A total of 353 patients of either sex, between 18- 65 years of age with supine blood pressure (BP) levels of systolic BP (SBP) of 140-200 mmHg and diastolic BP (DBP) of 95-114 mmHg were included. After a placebo run-in period of 2 weeks, each patient received a fixed dose combination of telmisartan/hydrochlorothiazide (40mg/12.5mg) once daily, for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety were assessed by physical examination, laboratory parameters and evaluation of adverse events. A total of 339 patients completed the study with 14 drop-out cases because of loss to follow-up. There was a significant fall (p<0.05) in both the SBP and DBP starting from the second week as compared to the baseline. Mean SBP had a significant reduction of 23.55 mmHg (15.0%) and 27.79 mmHg (18%) at the end of 6th and 8th week respectively, compared to baseline values. Mean DBP had also had a significant reduction of 12.51 mmHg (12.6%) and 15.17 mmHg (15.3%) at the end of 6th and 8th week respectively, compared to baseline values. This combination was well tolerated with only 3.9% of the total cases reporting mild adverse events like fatigue, dizziness, nausea, diarrhoea etc. The laboratory values were within normal limits. Fixed dose combination of telmisartan/hydrochlorothiazide (40 mg/12.5 mg) once daily has a significant therapeutic effect and a good tolerability profile in adult Indian patients with mild to moderate hypertension.

Eficácia do regime terapêutico empregando a associação de pantoprazol, claritromicina e amoxicilina, durante uma semana, na erradicação do Helicobacter pylori em pacientes com úlcera péptica / Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer

OBJETIVO: Estudo multicêntrico, aberto, delineado para determinar a eficácia da associação de pantoprazol, claritromicina e amoxicilina, na erradicação do Helicobacter pylori em pacientes portadores de úlcera péptica. MATERIAL E MÉTODOS: Setenta e um pacientes (36 mulheres, 35 homens, idade média 41,9 anos) provenientes de três centros universitários brasileiros (Belo Horizonte e Porto Alegre) com úlcera péptica confirmada à endoscopia e infecção por H. pylori comprovada por, no mínimo, dois testes diagnósticos. Os pacientes foram tratados com a associação de pantoprazol 40 mg, claritromicina 500 mg e amoxicilina 1,0 g, administrada duas vezes ao dia, durante 7 dias. RESULTADOS: Ao final do tratamento, os pacientes foram reexaminados para avaliação dos sintomas gastrointestinais, presença de eventos adversos e aderência ao tratamento. Nova endoscopia com biopsias e teste respiratório com 13C-uréia foram repetidos 60 dias após o término do tratamento para determinação das taxas de erradicação do microrganismo. Foram considerados H. pylori negativos os pacientes com, pelo menos, o teste respiratório com 13C-uréia e mais um teste (teste da urease ou histologia) negativos. Ao final do estudo 60/69 (87 por cento, 95 por cento = 78,9-94,8) pacientes erradicaram o H. pylori na análise por protocolo e 60/71 (84,5 por cento, 95 por cento = 76-92,9) na análise por intenção de tratamento. Um paciente interrompeu o tratamento devido à diarréia. Doze pacientes (16,9 por cento) apresentaram sintomas adversos e considerados de leve intensidade. CONCLUSAO: A associação de pantoprazol, amoxicilina e claritromicina por 7 dias constitui alternativa eficaz e bem tolerada para a erradicação do H. pylori em portadores de úlcera péptica no Brasil.