Inhibition of the RPS6KA1/FoxO1 signaling axis by hydroxycitric acid attenuates HFD-induced obesity through MCE suppression.

BACKGROUND: Because obesity is associated with a hyperplasia-mediated increase in adipose tissue, inhibiting cell proliferation during mitotic clonal expansion (MCE) is a leading strategy for preventing obesity. Although (-)-hydroxycitric acid (HCA) is used to control obesity, the molecular mechanisms underlying its effects on MCE are poorly understood. PURPOSE: This study aimed to investigate the potential effects of HCA on MCE and underlying molecular mechanisms affecting adipogenesis and obesity improvements. METHODS: Preadipocyte cell line, 3T3-L1, were treated with HCA; oil red O, cell proliferation, cell cycle, and related alterations in signaling pathways were examined. High-fat diet (HFD)-fed mice were administered HCA for 12 weeks; body and adipose tissues weights were evaluated, and the regulation of signaling pathways in epidydimal white adipose tissue were examined in vivo. RESULTS: Here, we report that during MCE, HCA attenuates the proliferation of the preadipocyte cell line, 3T3-L1, by arresting the cell cycle at the G0/G1 phase. In addition, HCA markedly inhibits Forkhead Box O1 (FoxO1) phosphorylation, thereby inducing the expression of cyclin-dependent kinase inhibitor 1B and suppressing the levels of cyclin-dependent kinase 2, cyclin E1, proliferating cell nuclear antigen, and phosphorylated retinoblastoma. Importantly, we found that ribosomal protein S6 kinase A1 (RPS6KA1) influences HCA-mediated inactivation of FoxO1 and its nuclear exclusion. An animal model of obesity revealed that HCA reduced high-fat diet-induced obesity by suppressing adipocyte numbers as well as epididymal and mesenteric white adipose tissue mass, which is attributed to the regulation of RPS6KA1, FoxO1, CDKN1B and PCNA that had been consistently identified in vitro. CONCLUSIONS: These findings provide novel insights into the mechanism by which HCA regulates adipogenesis and highlight the RPS6KA1/FoxO1 signaling axis as a therapeutic target for obesity.

Construction and validation of a prediction model for the risk of citrate accumulation in patients with hepatic insufficiency receiving continuous renal replacement therapy with citrate anticoagulation.

BACKGROUND: To construct and validate a prediction model of the risk of citrate accumulation in patients with hepatic dysfunction receiving continuous renal replacement therapy with regional citrate anticoagulation (RCA-CRRT), which reduces the risk of citrate accumulation. METHODS: All patients who received RCA-CRRT from 2021 to 2022 and were hospitalized in the First Affiliated Hospital of Zhejiang University were considered for study participation. Logistic regression analysis was used to identify the risk factors for citrate accumulation, based on which a nomogram model was constructed and validated in the validation group. RESULTS: Six factors were finally identified, from which a nomogram was created to predict the risk of citrate accumulation. The area under the curve of the prediction model was 0.814 in the training group and 0.819 in the validation group, and the model showed acceptable agreement between the actual and predicted probabilities. Decision curve analysis also demonstrated that the model was clinically useful. CONCLUSIONS: The model constructed from six factors reliably predicted the risk of citrate accumulation in patients with hepatic insufficiency who received RCA-CRRT.

Nafamostat mesylate versus regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding: a retrospective single-center study.

PURPOSE: The choice of continuous renal replacement therapy (CRRT) anticoagulation program for patients at high risk of bleeding has always been a complex problem in clinical practice. Clinical regimens include regional citrate anticoagulation (RCA) and nafamostat mesylate (NM). This study aimed to evaluate the efficacy and safety of these two anticoagulants for CRRT in patients at high risk of bleeding to guide their clinical use better. PATIENTS AND METHODS: Between January 2021 and December 2022, 307 patients were screened for this study. Forty-six patients were finally enrolled: 22 in the regional citrate anticoagulation group and 24 in the nafamostat mesylate group. We collected patients' baseline characteristics, laboratory indicators before CRRT, and CRRT-related data. We then performed a statistical analysis of the data from both groups of patients. RESULTS: In our study, the baseline characteristics did not differ significantly between the two groups; the baseline laboratory indicators before CRRT of patients in the two groups were not significantly different. The duration of CRRT was 600 min in the regional citrate anticoagulation (RCA) group, 615 min in the nafamostat mesylate (NM) group; the success rate was 90.7% in the RCA group, and 85.6% in the NM group, the anticoagulant efficacy between the two groups was comparable. There was no significant difference in the safety of anticoagulation between the two groups. We used Generalized Estimating Equations (GEE) to test whether different anticoagulation methods significantly affected the success rate of CRRT and found no statistical difference between RCA and NM. CONCLUSION: Our study suggests that nafamostat mesylate's anticoagulant efficacy and safety are not inferior to regional citrate anticoagulation for continuous renal replacement therapy in patients at high risk of bleeding.

Comparison of Class-Specific Side Effects Across Preventative Pharmacologic Therapies for Kidney Stone Disease.

INTRODUCTION: Clinical guidelines recommend monitoring for metabolic derangements while on preventive pharmacologic therapy for kidney stone disease. The study objective was to compare the frequency of side effects among patients receiving alkali citrate, thiazides, and allopurinol. METHODS: Using claims data from working-age adults with kidney stone disease (2008-2019), we identified those with a new prescription for alkali citrate, thiazide, or allopurinol within 12 months after their index stone-related diagnosis or procedure. We fit multivariable logistic regression models, adjusting for cohort characteristics like comorbid illness and medication adherence, to estimate 2-year measured frequencies of claims-based outcomes of acute kidney injury, falls/hip fracture, gastritis, abnormal liver function tests/hepatitis, hypercalcemia, hyperglycemia/diabetes, hyperkalemia, hypokalemia, hyponatremia, and hypotension. RESULTS: Our cohort consisted of 1776 (34%), 2767 (53%), and 677 (13%) patients prescribed alkali citrate, thiazides, or allopurinol, respectively. Comparing unadjusted rates of incident diagnoses, thiazides compared to alkali citrate and allopurinol were associated with the highest rates of hypercalcemia (2.3% vs 1.5% and 1.0%, respectively, P = .04), hypokalemia (6% vs 3% and 2%, respectively, P < .01), and hyperglycemia/diabetes (17% vs 11% and 16%, respectively, P < .01). No other differences with the other outcomes were significant. In adjusted analyses, compared to alkali citrate, thiazides were associated with a higher odds of hypokalemia (OR=2.01, 95% CI 1.44-2.81) and hyperglycemia/diabetes (OR=1.52, 95% CI 1.26-1.83), while allopurinol was associated with a higher odds of hyperglycemia/diabetes (OR=1.34, 95% CI 1.02-1.75). CONCLUSIONS: These data provide evidence to support clinical guidelines that recommend periodic serum testing to assess for adverse effects from preventive pharmacologic therapy.

Filter Lifespan, Treatment Effect, and Influencing Factors of Continuous Renal Replacement Therapy for Severe Burn Patients.

Continuous renal replacement therapy (CRRT) is often disrupted due to various factors, such as patient-related issues, vascular access complications, treatment plans, and medical staff factors. This unexpected interruption is referred to as non-selective filter stoppage and can result in additional treatment expenses. This study conducted a retrospectively analyzed 501 CRRT filters used in 62 patients with severe burns, lifespan and therapeutic effect of all filters were mainly analyzed, used logistic regression analysis was performed to identify risk factors associated with non-selective cessation filters. Out of 493 filters, 279 cases received heparin (56.60%), the median lifespan of the filter was 14.08 h (25th, 75th quantile: 7.30, 21.50); 128 cases were treated with nafamostat mesylate (26.00%), and the median lifespan of the filter was 16.42 h (10.49, 22.76); 86 cases were treated with sodium citrate (17.40%), and the median lifespan of the filter was 31.06 h (19.25, 48.75). In addition, significant differences were observed in the electrolyte index, renal function index, and procalcitonin levels before and after treatment with a single filter (P < .001). Multivariate logistic regression showed that the risk of non-selective cessation of sodium citrate anticoagulants was lower than that of heparin anticoagulation. Overall, CRRT is progressively becoming more prevalent in the treatment of patients with severe burns. The lifespan of individual filters and total patient treatment duration showed a consistent upward trend. The filter's lifespan was notably greater during sodium citrate anticoagulation when compared to nafamostat mesylate and heparin, meanwhile notably reducing the risk of non-selective cessation. Therefore, we recommend sodium citrate for anticoagulation in patients without any contraindications.

Réspuesta de los autores: Anticoagulación en las técnicas de depuración extrarrenal continuas en pacientes críticos / Reply: Anticoagulation for continuous renal replacement therapy in critically ill patients

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En el sellado del catéter venoso central en hemodiálisis, ¿presenta el uso de citrato respecto al uso de heparina menos complicaciones de infección? Una revisión de la literatura / In the central venous catheter sealing on hemodialysis, does the use of citrate with respect to the use of heparin have less complications of infection? A review of the literature

Introducción: La heparina es el fármaco anticoagulante de elección y de uso habitual en los servicios de hemodiálisis, en el procedimiento de permeabilización de los catéteres venosos centrales, aunque su uso no está exento de riesgos como la hemorragia. La infección asociada al catéter, bien por colonización del catéter o por bacteriemia, es el evento más importante y la segunda causa de mortalidad tras la enfermedad cardiovascular en el paciente en hemodiálisis. En este sentido, el uso del citrato se está presentando como una alternativa para el sellado de los catéteres venosos centrales, dado que tiene propiedades tanto anticoagulantes locales como antimicrobianas y podría ser más eficiente en la prevención o la reducción de la infección asociada al catéter. Objetivos: Identificar qué anticoagulante de uso en el sellado del catéter venoso central, la heparina o el citrato, presenta menos complicaciones de bacteriemia asociada al catéter y de colonización del catéter; Material y Método: se realizó una búsqueda bibliográfica a través del metabuscador EBSCOhost (Academic Search Premier, CINAHL) y las bases de datos PubMed, IME, Ibecs, LILACS, CUIDEN, Scopus y Cochrane Library, con la selección final de 15 documentos tras la aplicación de los límites de búsqueda, la eliminación de duplicados y la aplicación de los criterios de inclusión/exclusión. Los resultados más relevantes y actuales disponibles en la literatura científica presentaron cierta variabilidad, tanto en las concentraciones de anticoagulante como en la incidencia de infección. Resultados y Discusión: La numerosa evidencia sobre la bacteriemia asociada al catéter, tanto en relación con la concentración como en la combinación del anticoagulante de sellado, indica que el citrato 4% podría reducir la incidencia de bacteriemia, aunque el citrato asociado a antimicrobianos es más efectivo en la prevención de ésta respecto a la heparina sódica o el citrato exclusivo. Conclusiones: Aunque el uso de citrato sódico exclusivo no presenta claras ventajas en las complicaciones de infección asociada al catéter respecto a la heparina sódica, sí parecen demostrados sus beneficios a bajas (4%) o moderadas (30%) concentraciones, y especialmente, al combinarlo con antibióticos. Aún así, la asociación del citrato con antibióticos debe ser estudiada con profundidad por la comorbilidad del paciente, la reincidencia de infección y la resistencia antibiótica (AU)

Introduction: Heparin is the standard anticoagulant drug commonly used in hemodialysis services for the permeabilization of central venous catheters. Although it has risks like bleeding. Catheter-associated infection, either by colonization of the catheter or bacteraemia, is the most important event and the second cause of mortality following cardiovascular disease in the hemodialysis patient. In this sense, citrate use is being presented as an alternative for central venous catheter sealing because it has both local and antimicrobial anticoagulant properties and could be more efficient in preventing or reducing catheter-associated infection. Objectives: To identify which sealing anticoagulant of the central venous catheter, heparin or citrate, presents less complications of catheter-associated bacteremia and colonization of the catheter. Material and Method: A bibliographic search was performed through the EBSCOhost (Academic Search Premier, CINAHL) and PubMed, IME, Ibecs, LILACS, CUIDEN, Scopus and Cochrane Library databases, with the final selection of 15 documents after the application of search limits, removal of duplicates and the application of the inclusion/exclusion criteria. The most relevant and current results available in the scientific literature showed some variability, both in anticoagulant concentrations and in the incidence of infection. Results and Discussion: Numerous evidence on catheter-associated bacteremia, both in relation to the concentration and the combination of the sealed anticoagulant, indicates that 4% citrate could reduce the incidence of bacteremia. However, antimicrobial-associated citrate is more effective in preventing bacteremia than sodium heparin or exclusive citrate. Conclusions: Although the use of exclusive sodium citrate does not present clear advantages in the complications of catheter-associated infection with sodium heparin, the benefits are shown at low (4%) or moderate (30%) concentrations, especially when combined with antibiotics. Even so, the association of citrate with antibiotics should be studied according to patient comorbidity, recurrence of infection and antibiotic resistance (AU)

The use of neurovascular ultrasound versus digital subtraction angiography in acute ischemic stroke / O uso do ultrassom neurovascular comparado a angiografia digital no AVC isquêmico agudo

Cervical and intracranial arterial evaluation is an important issue for acute ischemic stroke (IS). Objective Compare the use of the neurovascular ultrasound examination (NVUE) to digital subtraction angiography (DSA) in acute IS patients for diagnosing significant extracranial and intracranial arteriopathy. Method Nonconsecutive patients with IS or transient ischemic attack admitted within 12 hours of the onset of symptoms were evaluated retrospectively. Standardized NVUE and DSA were done in all patients within the first 120 hours of hospital admission. Results Twenty-four patients were included in the study. Compared to DSA, the NVUE demonstrated 94.7% sensitivity and 100% specificity for identifying symptomatic extracranial and/or intracranial arteriopathy. Conclusion The standardized NVUE technique demonstrated high sensitivity and specificity compared to DSA for diagnosing arterial abnormalities in acute IS patients. .

A avaliação cervical e intracraniana é uma etapa importante no AVC isquêmico (AVCi) agudo. Objetivo Comparar o uso do ultrassom neurovascular (USNV) com técnica padronizada e a angiografia digital (AD) em paciente com AVCi agudo no diagnóstico de doença arterial significativa extra e/ou intracraniana. Método Pacientes com AVCi e AIT admitidos em até 12 horas do início dos sintomas foram retrospectivamente avaliados. Todos os pacientes foram submetidos a USNV e AD padronizado em até 120 horas da admissão. Resultados Vinte e quatro pacientes foram incluídos no estudo. Em comparação com a AD, o USNV apresentou sensibilidade de 94,7% e especificidade de 100% para o diagnóstico de doença arterial significativa extra e/ou intracraniana. Conclusão O uso de técnica padronizada de USNV demonstrou elevada sensibilidade e especificidade para o diagnóstico de doença arterial significativa extra e intracraniana quando comparado a AD. .

Alkaline citrate reduces stone recurrence and regrowth after shockwave lithotripsy and percutaneous nephrolithotomy

OBJECTIVE: To evaluate the preventive effects of alkaline citrate on stone recurrence as well as stone growth post-ESWL or PCNL in patients with calcium-containing stones. MATERIALS AND METHODS: A total of 76 patients with calcium calculi who were stone-free or had residual stones less than 4 mm following ESWL and PCNL were enrolled. All patients were independently randomized into two groups. The treated group (N = 39) was given 81 mEq per day of oral potassium-sodium citrate (27 mEq three times a day), and the untreated group (N = 37) serving as controls. Blood, twenty-four hour urine analysis, and plain KUB were measured and compared at the baseline and after 12 months. RESULTS: At baseline, hypocitraturia was found in 20 of 39 patients (46.05 percent) of Group I and 15 of 37 patients (40.5 percent) of Group II. At 12 months, hypocitraturia was found in 3 of 39 (7.69 percent) and 14 of 37 (37.83 percent) of Group I and Group II, respectively (p = 0.007). At the 12 month follow-up, of the stone-free group, 92.3 percent of the treated group and 57.7 percent of the control group were still stone free. Of the residual stone group, 30.8 percent and 9.1 percent of treated and control group were stone-free, respectively. The increased stone size found in 7.7 percent and 54.5 percent of treated and control groups, respectively. CONCLUSION: Sodium-potassium citrate provides positive effects on stone-forming activities in calcium stone patients suffering from urolithiasis following treatment with ESWL and PCNL procedures at the 12-month follow-up.

Comparação entre citrato trissódico e heparina como solução para selo de cateter em pacientes em hemodiálise / Comparison of trisodium citrate and heparin as catheter-locking solution in hemodialysis patients

INTRODUÇÃO: A elevada incidência de pacientes iniciando ou sendo mantidos em tratamento dialítico através de cateteres venosos tem aumentado o número de infecções da corrente sanguínea relacionadas aos cateteres e suas consequências, obrigando a busca de substâncias que tenham propriedades anticoagulantes e que também impeçam a contaminação dos mesmos. OBJETIVOS: Comparar a utilização de heparina e citrato trissódico como selo de cateteres de longa permanência quanto à ocorrência de pirogenia, bacteremia, internações hospitalares relacionadas à infecção, trombose e óbito. MÉTODOS: Estudo retrospectivo por meio de dados do registro de infecção do Programa de Controle e Prevenção de Infecções e Eventos Adversos, onde foram incluídos todos os pacientes que entre abril de 2006 e março de 2008 utilizaram cateteres de longa permanência. Nos primeiros 365 dias, o selo do cateter foi feito com heparina (Grupo Heparina) e nos 365 dias seguintes foi feito com citrato trissódico a 46,7 por cento (Grupo Citrato). Sessenta e cinco pacientes fizeram parte do estudo utilizando noventa e dois cateteres. Os grupos foram comparados para ocorrência de pirogenia, bacteremia, hospitalização, trombose de cateter e óbito. RESULTADOS: A ocorrência de bacteremia relacionada ao cateter e o tempo de hospitalização foram significantemente menores no Grupo Citrato. Houve uma tendência a menor ocorrência de hospitalização relacionada à infecção de acesso no Grupo Citrato (p = 0.055), e não houve diferença quanto à trombose de cateteres levando a disfunção. O tempo livre de bacteremia e de hospitalização foram maiores no Grupo Citrato. A ocorrência de bacteremia esteve associada a ser diabético e a pertencer ao Grupo Heparina. Na análise multivariada, apenas pertencer ao Grupo Heparina esteve associada à sua ocorrência.

INTRODUCTION: The high incidence of patients beginning dialysis treatment with venous catheters, as well as the growing number of patients with permanent catheter access, has increased catheter- related blood infections and their consequences. Thus the search for substances with anticoagulant properties that also prevent catheter contamination is necessary. OBJECTIVE: This study aimed at comparing heparin and trisodium citrate used as long-term catheter locking solutions regarding the occurrence of pyrogenic reaction, bacteremia, infection- related hospitalizations, thrombosis, and death. METHODS: Retrospective study on the infection data from the Infection and Adverse Event Prevention Control Program registry, which included all hemodialysis patients using long-term catheters from April, 2006 to March, 2008. During the first 365 days, catheters were locked with heparin (Heparin group) and, during the following 365 days, with 46.7 percent trisodium citrate (Citrate group). Sixty-five patients were included in the study using 92 catheters. The groups were compared regarding the occurrence of pyrogenic reaction, bacteremia, hospitalization, catheter thrombosis, and death. RESULTS: The catheter-related bacteremia episodes were significantly lower and hospitalization time was significantly shorter in the Citrate group when compared with those in the Heparin group. A tendency towards a lower occurrence of access site infection-related hospitalization was observed in the Citrate group (p = 0.055), and no difference was observed in catheter thrombosis leading to dysfunction between groups. Bacteremia-free and hospitalization-free times were longer in the Citrate group. The occurrence of bacteremia was associated with the presence of diabetes and heparin use. In multivariate analysis, being in the Heparin group was the only factor associated with bacteremia.

Estudio comparativo del sellado de catéteres con citrato trisódico o heparina sódica más gentamicina / Comparative study of catheter sealing with trisodium citrate or sodium heparin plus gentamicin

La cateterización de una vena central como acceso vascular para la hemodiálisis supone una alternativa rápida y segura, que permite ser utilizada inmediatamente y obtener flujos sanguíneos óptimos. Sin embargo, el uso de catéteres no está exento de complicaciones, lo que provoca una alta morbilidad aumentando las cargas de trabajo y el gasto económico. La colonización y la formación de una película producida por las bacterias (biofilm) son considerados factores de riesgo, tanto en las infecciones relacionadas con catéter como en trombosis intraluminal. Para reducir estas complicaciones, utilizábamos como profilaxis un protocolo de sellado en los catéteres con una solución de heparina al5% más gentamicina. Sin embargo, debido a complicaciones hemorrágicas, infecciosas y a una exposición constante del paciente a antibióticos, se decidió cambiar de protocolo a una solución de citratotrisódico concentrado (46,7%) por sus propiedades anticoagulantes y antimicrobianas. Nuestro objetivo es valorar la implantación de un protocolo con citrato trisódico concentrado para el sellado de los catéteres. Los resultados obtenidos en este estudio son: importante descenso en el número de infecciones; menor número de manipulaciones; menor utilización de antibióticos, evitando crear resistencias y sensibilizaciones; dosis dialítica adecuada, disminución del coste económico de las cargas de trabajo y de la morbilidad de los pacientes (AU)

Placing a catheter in a central vein as vascular access for haemodialysis is a quick and safe alternative that can be used immediately and lets optimal blood flows be obtained. However, the use of catheters is not free from complications, causing high morbility and increasing the work load and economic cost. The colonization and formation of a film produced by bacteria (biofilm) are considered risk factors, both in infections related to the catheter and in intraluminal thrombosis. To reduce these complications, we used a catheter sealing protocol with a5% heparin solution plus gentamicin. However, due to haemorrhagic complications, infections and a constant exposure of the patient to antibiotics, it was decided to change the protocol to a concentrated(46.7%) trisodium citrate solution because of its anticoagulant and antimicrobial properties. Our aim is to evaluate the implementation of a protocol with concentrated trisodium citrate for sealing catheters. The results obtained in this study are: important fall in the number of infections; less handling; less use of antibiotics, preventing the creation of resistance and sensitivities; adequate dialytic dose, reduction in economic cost of work load and in patient morbility (AU)

Anticoagulação em terapias contínuas de substituição renal / Anticoagulation in continuous renal replacement therapies (CRRT)

As terapias contínuas de substituição renal (TSRC) são comumente usadas na maioria de pacientes criticamente enfermos com indicação de diálise. O sucesso das TSRC depende de um protocolo de anticoagulação eficiente para manter permeável o circuito de diálise, minimizando complicações como sangramento por anticoagulação excessiva ou a necessidade da troca do sistema por coagulação do mesmo, por anticoagulação insuficiente. Vários fatores podem contribuir para a trombose do circuito de diálise, como a velocidade do fluxo de sangue através do circuito, o cateter de diálise, o tipo de membrana utilizada no filtro dialisador e, também, o tipo de terapia prescrita. A heparina não fracionada (HNF) é o anticoagulante mais utilizado para as diferentes técnicas de diálise e, mais recentemente, as heparinas de baixo peso molecular (HBPM) têm se mostrado seguras e efetivas para TRSC. Em pacientes criticamente enfermos que freqüentemente têm contra-indicação para anticoagulação sistêmica, existe a alternativa da anticoagulção regional com citrato trissódico, método eficiente e seguro, se aplicado com controle metabólico estrito. A anticoagulação regional com HNF/protamina tem seu uso limitado, atualmente, por apresentar muitas complicações decorrentes de efeitos adversos da protamina. Na impossibilidade do paciente ser anticoagulado, ou se a anticoagulação regional com citrato não for disponível, a lavagem freqüente do circuito de diálise com solução salina é a única alternativa aplicável. Novas drogas ainda não disponíveis no Brasil, como prostaglandinas, hirudina recombinante, argatroban e nafamostat podem ser utilizadas em pacientes com contra-indicação para heparinização.

Continuous renal replacement therapies (CRRT) are commonly used in the majority of critically ill patients who need dialysis. Treatment success depends on an efficient anticoagulation protocol devised to maintain the dialysis circuit unclotted, with minimal complications such as bleeding due to excessive anticoagulation. Several features can contribute to dialysis circuit thrombosis, such as the speed of pump blood flow, dialysis catheter, type of dialyzer membrane and also, the type of technique prescribed. Unfractioned heparin (UFH) is the anticoagulant most used in CRRT. Recently, low-molecular weight heparins (LMWH) have been shown to be safe and effective drugs for this purpose. In critically ill patients, who frequently have contraindications to systemic anticoagulation, regional anticoagulation with trisodium citrate is an increasingly accepted method due to its safety and efficiency if applied under strict metabolic control. Regional anticoagulation with UFH/protamin now has limited use because of side effects related to protamin. If the patient has contraindication to systemic anticoagulation or if regional anticoagulation with citrate is not available, continuous flushing of circuit dialysis with saline is the only applicable alternative. In patients with contraindication to heparinization, new drugs not yet available in Brazil, such as prostaglandins, recombinant hirudin, argatroban and nafamostat can be used.

La transfusión de sangre citratada: Luis Agote y una polémica de prioridad / Citrated blood transfusion: Luis Agote and an argument about priority

Este artículo se refiere a la polémica de 1914 - 1915 entre el argentino Luis Agote, el norteamericano Robert Lewinsohn y el belga A. S. Hustin, sobre la prioridad en el descubrimiento de las propiedades anticoagulantes del citrato de sodio sobre la sangre humana. Se analizan las características científicas del hallazgo y la diferente forma utilizada por cada uno de ellos para divulgarlo, como asimismo los factores éticos y geopolíticos sobre la polémica de prioridad.

La transfusión de sangre citratada: Luis Agote y una polémica de prioridad / Citrated blood transfusion: Luis Agote and an argument about priority

Este artículo se refiere a la polémica de 1914 - 1915 entre el argentino Luis Agote, el norteamericano Robert Lewinsohn y el belga A. S. Hustin, sobre la prioridad en el descubrimiento de las propiedades anticoagulantes del citrato de sodio sobre la sangre humana. Se analizan las características científicas del hallazgo y la diferente forma utilizada por cada uno de ellos para divulgarlo, como asimismo los factores éticos y geopolíticos sobre la polémica de prioridad. (AU)

Tratamiento metafiláctico (preventivo) en los principales tipos de litiasis urinaria / Metaphilactic treatment (preventive) in types essential of urinary lithiasis

Este trabajo de investigación tiene como objetivo primordial, destacar la gran importancia que tiene el tratamiento metafiláctico (tratamiento preventivo), en la evolución clínica de los pacientes afectados de cálculos urinarios. Son una serie de medidas que persiguen un fin claro y útil, que es evitar en lo posible la reformación de cálculos dentro de las vías urinarias, con la posibilidad de complicaciones de variados grados, que comprometerían al final, la salud renal y la salud general del paciente afecto de este tipo de patología urológica. Con un fin didáctico y de fácil aprendizaje dividiré dichos tratamientos, de acuerdo al tipo de cálculo en particular. Se debe hacer hincapié que el tratamiento de los cálculos urinarios no empieza y termina con la remoción del cálculo. Por el contrario, se debe realizar una exhaustiva pesquisa de laboratorio (con sistemáticas especiales) para determinar con precisión, tanto a nivel sérico, como a nivel urinario, qué tipo de trastorno metabólico tiene el paciente, qué le está ocasionando el cuadro de litiasis urinaria, muchas veces a repetición. Y que después de la posible y necesaria extracción del cálculo en las vías urinarias, vendrá un aspecto que, sin duda alguna, es el menos conocido y por lo tanto el menos utilizado, como es el tratamiento preventivo o metafiláctico a través de una serie de argumentos médicos, dietéticos y de hábitos en general y que presenta en la mayoría de los casos, la diferencia entre un paciente "curado" y un paciente con episodios de litiasis recidivante, lo cual afectará negativamente la calidad de vida de dicho paciente

Evaluación del efecto del hipoclorito de sodio, ácido cítrico y ácido etileno diaminotetracético en la remoción del barro dentinario de los conductos tratados endodónticamente / Evaluation of the effect of sodium hypochlorite, citric acid and EDTA in smear layer removal from endodontically treated root canals

La remoción del barro dentinario, que se forma por la instrumentación de los conductos radiculares, es importante para el aumento de la permeabilidad, por limpiar los orificios de los túbulos dentinarios. En este estudio "in vitro" se utilizaron 90 dientes unirradiculares de humanos, distribuidos en 3 grupos de 30, instrumentados con limas K (15-40), teniendo el hipoclorito de sodio (NaOCl) al 1 por ciento como solución irrigante. En el primer grupo, se utilizó únicamente el NaOCl; en el segundo y tercer grupo, además de la solución irrigante, se añadieron respectivamente el ácido cítrico al 50 por ciento y el ácido etileno diaminotetracético (EDTA) como soluciones auxiliares. La penetración del colorante Rodamina B en la masa dentinaria evidenció el aumento de la permeabilidad. Los resultados analizados permitieron concluir que la solución irrigante asociada con la solución auxiliar de EDTA fue, entre las probadas, aquella que presentó mejores efectos tras comprobación estadística (AU)

O emprego do citrato de clomifeno e gonadotrofina de mulher menopausada como alternativa de hiperestimulaçäo ovariana em pacientes com resposta idiopática inadequada na fertilizaçäo in vitro / Clomiphene citrate and gonadotropins of woman in menopause as an alternative approach to ovarian hyperstimulation in idiopatic poor response for in vitro fertilization

OBJETIVO: Avaliar os efeitos do esquema de estimulaçäo ovariana com citrato de clomifeno (CC)/gonadotrofina de mulher menopausada (hMG) nos resultados da fertilizaçäo in vitro e transferência de embriöes (FIVETE) em um grupo de pacientes que apresentaram resposta ovariana inadequada em ciclos prévios de FIVETE estimulados com um análogo do GnRH e gonadotrofinas (protocolo longo). MÉTODO: Os resultados de FIVETE em ciclos estimulados com CC/hMG e com o protocolo longo de uma mesma paciente foram comparados. Oito pacientes (grupo I) que apresentaram uma resposta ovariana idiopática inadequada (idade: < 38 anos, FSH<15 mU/mL, E2<60pg/mL, ciclos menstruais regulares e ausência de cirurgia ovariana) ao protocolo longo em 11 ciclos de FIVETE (grupo Ia), foram estimuladas com CC/hMG em 20 ciclos (grupo Ib). Administrou-se CC 100 mg/dia por 5 dias a partir do 3§ dia do ciclo e o hMG 150 UI/dia foi iniciado no 5§ dia, sendo a dose modificada de acordo com a resposta da paciente. Dezenove ciclos de 15 pacientes com resposta ovariana adequada ao protocolo longo, durante o mesmo intervalo de tempo, foram incluídas neste estudo como grupo controle (grupo II). Casais com fator masculino de infertilidade foram excluídos. RESULTADOS: As pacientes avaliadas näo apresentaram diferença em termos de idade, duraçäo da infertilidade e do índice de massa corpórea. Embora a duraçäo do estímulo ovariano tenha sido similar nos 3 grupos: 10,1 + 0,76, 10,9 + 0,34 e 10,3 + 0,21 dias para os grupos Ia, Ib e II, respectivamente, o número médio de ampolas de hMG utilizado no grupo Ib (13,6 + 1,36) foi significativamente menor (p<0.001) quando comparado aos grupos Ia e II (49,9 + 3,20, 43,7 + 2,73; respectivamente). A taxa de cancelamento foi de 36,4 por cento, 25,0 por cento e 0 por cento (grupos Ia, Ib e II; respectivamente), näo revelando diferença entre os grupos Ia e Ib. Os números médios de oócitos MII inseminados e fertilizados foram de 4,9 + 0,8 e 1,3 + 0,4 no grupo Ia e de 4,4 + 0,3 e 2,1 + 0,2 no grupo Ib, näo mostrando diferença entre os grupos. Contudo, os números médios de oócitos MII inseminados e fertilizados no grupo II, 11,4 + 2,0 (p<0.01) e 7,9 + 2,0 (p=0.01), respectivamente, foram significativamente maiores quando comparados aqueles do grupos Ia e Ib...

Papel de la insulina y andrógenos sobre la respuesta ovulatoria al citrato de clomifeno en el síndrome de ovarios poliquísticos / Paper of the insulin and androgens on its relation to clomiphene citrate ovulatory response in polycystic ovary syndrome

Con el objeto de evaluar la secreción de insulina estimulada por glucosa oral, andrógenos séricos y la respuesta ovulatoria al citrato de clomifeno en el síndrome de ovarios poliquísticos, 23 mujeres con diagnóstico de síndrome de ovarios poliquísticos y 10 mujeres normales fueron evaluadas en un estudio prospectivo realizado en el Hospital Universitario de Los Andes, Mérida, Venezuela. La respuesta de insulina durante una prueba de tolerancia a la glucosa fue expuesta como área de insulina bajo la curva. En todas las pacientes la ovulación fue inducida con clomifeno: 100 mg/día por 5 días. La ovulación fue evaluada por ultrasonido abdominal diario y cuantificación de progesterona sérica, la cual se logró en el 52,17 por ciento y una respuesta anovulatoria fue observada en el 47,83 por ciento de las pacientes. Dentro del grupo anovulatorio, el folculo luteinizado no roto fue observado en el 26,9 por ciento de las pacientes. No hubo diferencias significativas entre los grupos ovulatorio y anovulatorio. La androstenediona sérica fue significativamente más alta en el grupo anovulatorio que en el grupo ovulatorio. Probablemente los niveles elevados de insulina pueden contribuir al aumento de la síntesis ovárica de andrógenos, lo cual favorece la atresia folicular y por consiguiente, la anovulación y esterilidad

Regeneración tisular guiada en periodoncia. Estado actual. Primera parte. Reporte de casos clínicos / Guided tissue regeneration in periodontics. Current status. First part. Report of clinical cases

En este artículo se presentan en una forma actualizada, los aspectos básicos de la terapia periodontal regenerativa, haciendo énfasis en la regeneración tisular guiada (R.T.G.) por medio de barreras reabsorbibles y no reabsorbibles. Se reportan casos clínicos, en los cuales se realizó la técnica de R.T.G. con membrana de Gore-Tex, sin acondicionamiento radicular y con acondicionadores radiculares como el ácido cítrico y la tetraciclina Hcl (clorhidrato de tetraciclina)