Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: Skew toward M2 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat׳s claw", and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages. MATERIAL AND METHODS: In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25µM) and LPS (100ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers. RESULTS: In human primary monocytes, the incubation of MTP for 24h reduced the number of classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1ß, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages. CONCLUSIONS: Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response.

[Intraoperative hemodynamic monitoring using transesophageal echocardiography in orthopedic surgery]. / Alta utilidad de monitorización hemodinámica con ecocardiografía transesofágica intraoperatoria en cirugía ortopédica.

BACKGROUND: Orthopedic surgery is commonly performed in elderly patients with higher cardiovascular surgical risk. Hemodynamic monitoring in these patients may prevent perioperative complications. AIM: To assess the usefulness of transesophageal echocardiography (TEE) for intraoperative cardiovascular monitoring during orthopedic surgery. MATERIAL AND METHODS: Patients older than 65 years subjected to orthopedic surgery using general anesthesia and with a high cardiovascular risk were studied. Intraoperative TEE was performed to assess intravascular volume, myocardial contractility and the presence of myocardial ischemia. RESULTS: Fifty three patients aged 72+/-5 years were studied. Hemodynamic stability was detected in 68% of patients, mainly reflected as episodes of hypovolemia. Myocardial ischemia was detected in two patients and embolic episodes in six (11%). CONCLUSIONS: Intraoperative TEE was useful for the hemodynamic evaluation of patients with high cardiovascular risk.

Alta utilidad de monitorización hemodinámica con ecocardiografía transesofágica intraoperatoria en cirugía ortopédica / Intraoperative hemodynamic monitoring using transesophageal echocardiography in orthopedic surgery

Background: Orthopedic surgery is commonly performed in elderly patients with higher cardiovascular surgical risk. Hemodynamic monitoring in these patients may prevent perioperative complications. Aim: To assess the usefulness of transesophageal echocargiography (TEE) for intraoperative cardiovascular monitoring during orthopedic surgery. Material and methods: Patients older than 65 years subjected to orthopedic surgery using general anesthesia and with a high cardiovascular risk were studied. Intraoperative TEE was performed to assess intravascular volume, myocardial contractility and the presence of myocardial ischemia. Results: Fifty three patients aged 72±5 years were studied. Hemodynamic stability was detected in 68 percent of patients, mainly reflected as episodes of hypovolemia. Myocardial ischemia was detected in two patients and embolic episodes in six (11 percent). Conclusions: Intraoperative TEE was useful for the hemodynamic evaluation of patients with high cardiovascular risk.

Secretion of thymidine kinase to increase the effectivity of suicide gene therapy results in the loss of enzymatic activity.

Low efficiency of gene transfer is one of the major limitations of gene therapy. A solution to this problem may be transmission; by modification of the transgene, the gene product can be secreted and internalized by the surrounding cells. Cancer gene therapy using the herpes simplex thymidine kinase (HSV-TK) suicide gene is a promising treatment, and TK has been used in clinical trials with some success. However, this kind of therapy has limited efficacy due to the low level of gene transfer reached. A modified TK protein, capable of migrating from the producing cell to neighboring cells, would result in a greater proportion of cells affected by the treatment. As a first step towards transmission, we constructed a secretory form of HSV-TK by including the Igkappa leader peptide in the gene. An endoplasmatic reticulum export signal was added to the construct to further improve its secretion. Secretion and protein production in cancer cells, the enzymatic activity of the modified proteins and the ability of the modified TK to sensitize cancer cells to ganciclovir were tested. Addition of the Igkappa leader resulted in high levels of secretion of HSV-TK, with up to 70% of the total amount of protein secreted. Inclusion of an ER export signal did not further improve secretion. The enzyme activity of the secreted TK however, was decreased when compared to native TK. This study is the first to report on secretion of TK, and provides a first step in a novel strategy to improve the efficiency of cancer gene therapy. The loss of function in secreted TK however, may present a major hurdle in the development of a transmitted form of TK.

[Prevalence and prognosis significance of euthyroid sick syndrome in critical illness]. / Prevalencia y significación pronóstica del síndrome del enfermo eutiroideo en patología crítica.

The prevalence and prognosis of the sick euthyroid syndrome (SES) was studied in 91 patients admitted to the ICU by determining free thyroid hormones (FT3 and FT4), T3 reverse (rT3) and thyrotropin (TSH). The prevalence of SES was lower than expected, type I being higher that type II. The acute coronary syndrome had a lower prevalence of SES than other clinical conditions. Patients who developed type II SES had a higher mortality rate.

[Occupational accidents at an Acute Care Hospital]. / Accidentes de trabajo en un hospital de agudos.

BACKGROUND: To obtain a better knowledge of the determining factors and circumstances giving rise to occupational accidents will foster the implementation of corrective measures. The aim of this study is that of describing the trend of occupational accidents (OA's) over the course of time and of determining the risk factors regarding workers being forced to take time off for sick leave at the "Dr. Peset" Hospital in Valencia. METHODS: Description and retrospective analysis of the occupational accidents having occurred at the "Dr. Peset" Hospital in Valencia throughout the 1992-1995 period. The trend and seasonality of the series (seasonal indexes, SI's) were estimated by deterministic methods. A logistic regression model was employed to identify the factors providing a prior indication workers being off on sick leave and to determine the probability of the occurrence thereof. RESULTS: The highest OA rates were found among the kitchen and laundry workers (10.00 OA's per 100 workers/year). The OA's involving sick leave continued to show a trend of around zero, February being the months showing the highest SI (SI = 139.8). Those processed without sick leave showed an upward trend (r2 = 0.23, p < 0.0001), May being the month involving the largest number of casualties (SI = 134.2). The probability of an accident resulting in a worker being forced to take time of for sick leave increases significantly with age, when the accident in question takes place in the afternoon/evening, if it takes place in the kitchen/laundry, and if a sprain or tendinitis is involved. CONCLUSIONS: The measures taken involving the number of casualties entailing OA's which result in temporary incapacity should revolve around the less-skilled positions and the kitchen and laundry departments.

[Factors associated with inadequate response to hepatitis B vaccination in health care personnel]. / Factores asociados a una respuesta inadecuada a la vacunación contra la hepatitis B en personal sanitario.

BACKGROUND: The recombinant hepatitis B vaccine provides immunity in approximately 95% of all cases, but there is a certain percentage which responds insufficiently. The purpose of this work consists of assessing the factors which are linked to an inadequate immune response. METHODS: This is an observational, analytical study in which a retrospective follow-up is made of a group of subjects vaccinated to prevent against hepatitis B (HBV). The variables of interest of the health care personnel meeting the requirements to be included in this study in Health Care District No. 9 of the Autonomous Region of Valencia (No. 827) were gathered. Following vaccination, the titration of surface antibodies (antiHB's) was determined for checking the response, levels of over 10 m UI/ml being considered to provide protection. RESULTS: An adequate serum changeover was achieved in 94.4% of those vaccinated. The low-degree or zero response to the vaccine was significantly linked independently to variables such as male gender, age, the body mass index (BMI) and the habit of smoking. Drinking alcohol and the levels of GPT, although they did not react significantly with the response to the vaccine, were possibly misleading factors. CONCLUSION: The immunogenicity of this vaccine is satisfactory. It is important to quantify the levels of antiHB's, especially when factors predicting a poor response are involved. Therefore, it is possible to identify those which require a booster shot and those showing no response, hence avoiding situations involving a false sense of being protected against HBV.

Presión inspiratoria máxima en artritis reumatoide / Maximal inspiratory pressure in rheumatoid arthritis

En 10 pacientes portadoras de artritis reumatoide se evaluó la fuerza global de la musculatura inspiratoria a través de la presón inspiratoria máxima (PIM). Seis sujetos presentaron alteraciones radiológicas pulmonares, 6 manifestaciones de tos y 2 de disnea. La PIM resultó significativamente disminuida (p< 0,05) con respecto al grupo control normal. En 8 pacientes se encontró que a mayor duración de la terapia esteroidal, la PIM era significativamente menor (p< 0,05). Se concluye que en el grupo estudiado, existe una disfunción de la musculatura inspiratoria probablemente en relación a la terapia esteroidal, la que se explicaría en parte por la presencia de una miositis esteroidal y/o reumática de acuerdo a lo publicado recientemente

Reporte del primer caso de rinosporidiosis en la provincia Ciego de Avila, Cuba / First case report of rhinosporidiosis at Ciego de Avila, Cuba

Se presenta el primer caso de rinosporidiosis diagnosticado en la provincia Ciego de Avila, Cuba, analizándose las características clinico epidemiológicas del caso. Paciente de 13 años de edad, de sexo masculino, proveniente de un área rural que presentaba localización nasal de las lesiones. Se revisa la literatura al respecto