The effect of down-regulation of Smad3 by RNAi on hepatic stellate cells and a carbon tetrachloride-induced rat model of hepatic fibrosis

Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs). The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Colα1, Col3α1, Col4α1, respectively) was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30) and the treated group (N = 20) were injected subcutaneously with 40% (v/v) carbon tetrachloride (CCl4)-olive oil (3 mL/kg), and the normal control group (N = 30) was injected with olive oil (3 mL/kg). In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg) into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS), and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid). The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05) and the serum indices were greatly improved (P < 0.01). These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.

Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg,ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg,ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.

Effects of different general anesthetics on serum hemolysis and hepatic and muscular glycogenolysis in rats

Anesthetics can affect the structure and biological function of tissues and systems differentially. The aim of the present study was to compare three injectable anesthetics generally used in experiments with animals in terms of the degree of hemolysis and glycogenolysis occurring after profound anesthesia. Twenty-four male Wistar rats (330-440 g) were divided into three groups (N = 8): chloral hydrate (CH), ketamine + xylazine (KX), Zoletil 50® (zolazepam and tiletamine) + xylazine (ZTX). After deep anesthesia, total blood was collected. The liver and white (WG) and red gastrocnemius (RG) muscles were also immediately removed. The degree of serum hemolysis was quantified on the basis of hemoglobin concentration (g/L). Hepatic and muscular glycogen concentrations (mmol/kg wet tissue) were quantified by the phenol-sulfuric method. The CH and KX groups exhibited serum hemolysis (4.0 ± 2.2 and 1.9 ± 0.9 g/L, respectively; P < 0.05) compared to the ZTX group, which presented none. Only KX induced elevated glycogenolysis (mmol/kg wet tissue) in the liver (86.9 ± 63.2) and in WG (18.7 ± 9.0) and RG (15.2 ± 7.2; P < 0.05). The CH and ZTX groups exhibited no glycogenolysis in the liver (164.4 ± 41.1 and 176.8 ± 54.4, respectively), WG (28.8 ± 4.4, 32.0 ± 6.5, respectively) or RG (29.0 ± 4.9; 25.3 ± 8.6, respectively). Our data indicate that ZTX seems to be an appropriate general anesthetic for studies that seek to simultaneously quantify the concentration of glycogen and serum biochemical markers without interferences. ZTX is reasonably priced, found easily at veterinary markets, quickly induces deep anesthesia, and presents a low mortality rate.

Forty Years of the United Nations General Assembly Resolution 3379 (XXX) on Zionism and Racism: the Brazilian Vote as an instance of United States - Brazil Relations

Abstract In 1975, Brazil voted in favor of the United Nations General Assembly resolution 3379 (XXX), equating Zionism with a form of racism. Focusing on the decision-making process of president Ernesto Geisel's (1974-1979) foreign policy, "responsible pragmatism", this article discusses how the ultimate decision to vote in favor of resolution was taken taking into account mainly US-Brazil relationship.

Epidemiología de la enfermedad de Chagas, Departamento General Paz, Argentina

OBJETIVO: El objetivo del presente trabajo fue investigar la colonización por triatominos en ambientes domésticos y peridomésticos y evaluar la seroprevalencia de infectados chagásicos en localidades rurales. MÉTODOS: La investigación se realizó en General Paz, Corrientes, Argentina. Las viviendas y peridomicilios se seleccionaron mediante un muestreo simple al azar. La búsqueda de triatominos se efectuó por el método captura/hora/hombre. Los insectos se identificaron taxonómicamente y se clasificaron según sexo y edad. La infección por Trypanosoma cruzi se detectó por observación directa de las heces al microscopio y por la técnica de la reacción en cadena de la polimerasa (PCR). Se evaluaron serológicamente a pobladores voluntarios mediante las técnicas de hemaglutinación indirecta (HAI) y ensayo inmunoenzimático (ELISA). Se hallaron los índices de infestación, densidad, colonización, infección natural y dispersión. RESULTADOS: Se analizaron 42 viviendas y 50 peridomicilios. En el domicilio los índices de infestación e infección de Triatoma infestans fueron 23,8 y 19,4 respectivamente. Los índices de densidad, colonización y dispersión fueron 2,1; 47,0 y 50,0 respectivamente. La infestación del peridomicilio por T. infestans fue 5,9% y por T. sordida 11,8%. T. sordida resultó infectada por Trypanosoma cruzi en un 2,0%. La seroprevalencia al T. cruzi de los 85 pacientes fue del 22,3%. CONCLUSIONES: Se estima que en el área investigada la transmisión del T. cruzi está interrumpida. Sin embargo, la presencia de infectados humanos y de T. infestans parasitadas posibilitan el reinicio del ciclo de transmisión. Se proponen acciones de rociado con insecticidas con el objeto de eliminar las poblaciones del vector.

Factores asociados a mortalidad perinatal en el hospital general de Chiapas, México

OBJETIVO: El objetivo del estudio es identificar factores socioeconómicos, gineco-obstétricos y del producto asociados a mortalidad perinatal. MÉTODOS: Se realizó un estudio de casos y controles pareado. Se consideró caso a los nacidos vivos o muertos que nacieron y fallecieron entre las 28 semanas de gestación a los 7 días de vida extrauterina. y control al producto nacido vivo entre las 28 semanas de gestación y los 7 días de vida extrauterina. Los datos se obtuvieron de los expedientes clínicos hospitalarios. Se estudiaron 99 casos y 197 controles. Se hizo un análisis estadístico utilizando Stata 6.0. RESULTADOS La media de edad de la madre fue de 24.82 años y del producto de 37.78 semanas de gestación. El promedio de peso del producto fue de 2,760 gramos. Los factores asociados a mortalidad perinatal fueron: ocupación del padre agricultor (RM ajustada 3,31; IC 95% 1,26-8,66); índice de riesgo obstétrico alto (RM ajustada 10,57; IC 95% 2,82-39,66), antecedente de cesárea (RM ajustada 2,75; IC 95% 1,37-5,51); cinco y más consultas prenatales (RM ajustada 4,43; IC 95% 1.86-10,54); producto pretérmino (RM ajustada 9,20; IC 95% 4,39-19,25). CONCLUSIONES: Los resultados muestran que es necesario implementar medidas de prevención y control que aseguren la identificación del riesgo en las mujeres embarazadas, con el fin de abatir la incidencia de mortalidad perinatal.

Study of a cutaneous leishmaniasis outbreak in General Vedia, Province of Chaco, 1996

Between March and July 1996, a focalized epidemic outbreak of cutaneous leishmaniasis in General Vedia, province of Chaco, associated to the gallery forest of the Oro river was verified. The incidence rate in the area, which was 0-2/000 cases in preceding years, reached 8/000 cases in 1996. The risk of symptomatic infection was similar between sexes, but was different when analizing the different age groups by sex, suggesting a greater relative importance of the peridomestic transmission for the females and of the transmission in the subtropical forest for the males. Specimens of Lutzomyia intermedia, a species already incriminated as a vector of Leishmaniasis in other provinces of northern Argentina, were captured and identified in the focus locality in May 1996. The possible causes of the outbreak related to the climatic variables and the vector abundance are analyzed and the results in the framework of possible preventive and control activities are discussed.

Seroprevalence of antibodies to Venezuelan equine encephalitis complex (subtypes IAB and VI) in humans from General Belgrano Island, Formosa, Argentina

This work presents the results of the detection of antibodies (immunoglobulin G) for subtypes I and VI of VEE viruses complex (Togaviridae family) in people from the General Belgrano island, Formosa province (Argentina). The prevalence of neutralizing (NT) antibodies for subtype VI was from 30% to 70% and the prevalence of antibodies inhibitory of hemagglutination (HI) was of 0% in the first and second inquiry respectively. For the subtype IAB the prevalence of NT antibodies was from 13% to 3.6%, similar to the prevalence total for both subtypes. HI antibodies were not detected in any inquiries for any subtype. It was observed that both subtypes circulate simultaneously, while subtype VI remains constant with some peaks, subtype I was found in low level.

Frequency of human leukocyte antigen (hla) in patients with malaria and in the general population of Humaitá county, Amazonas state, Brazil

In August 1983,85 inhabitants of the municipality of Humaitá, Amazonas State, Brazil were studied to determine the prevalence of antigens to HLA-A, -B, -C and DR. Thirty-eight were sick with malaria due to Plasmodium falciparum. All subjects were examined for splenomegaly, blood parasitaemia and antibodies to malaria. They constituted three groups: 1) 25 subjects native to the Amazon region who had never had malaria; 2) 38 Amazonian subjects who had malaria in the past or currently had an infection; 3) 22 patients with malaria who had acquired the infection in the Amazon Region but came from other regions of Brazil. Blood was taken from each person, the lymphocytes were separated and typed by the test of microlymphocytotoxicity. There was a high frequency of antigens that could not be identified in the groups studied which suggests the existence of a homozygote or phenotype not identified in the population. There was a high frequency of the phenotype Ag(W24) (44.7%) in group 2 when compared with group 1 (32%) or group 3 (9%). Also the individuals in group 2 showed an elevated frequency of antigen DR(4)80%) when compared with group 1 (36.6%) or group 3 (16.6%). These observations suggest the possibility of a genetic susceptibility to malaria among Amazonian residents and indicate a necessity for more extensive studies of the frequency of HLA antigens among inhabitants of this endemic malarial zone.

Leprosy in Buriticupu, state of Maranhão: active search in the general population

INTRODUCTION: This study was developed to evaluate the situation of leprosy in the general population of the municipality of Buriticupu, State of Maranhão, Brazil. METHODS: We used the method of active search to identify new cases from 2008 to 2010. Bacilloscopy of intradermal scrapings was performed in all patients with skin lesions compatible with leprosy, and histopathological examination in those who had doubts on the definition of the clinical form. RESULTS: The study included 19,104 individuals, with 42 patients diagnosed with leprosy after clinical examination, representing a detection rate of 219.84 per 100,000 inhabitants. The predominant clinical presentation was tuberculoid with 24 (57.1%) cases, followed by borderline with 11, indeterminate with four, and lepromatous with three cases. The study also allowed the identification of 81 patients with a history of leprosy and other skin diseases, such as pityriasis versicolor, dermatophytosis, scabies, vitiligo, and skin carcinoma. The binomial test showed that the proportion of cases in the headquarters was significantly higher than that in the villages (p = 0.04), and the generalized exact test showed that there was no association between age and clinical form (p = 0.438) and between age and gender (p = 0.083). CONCLUSIONS: The elevated detection rate defines the city as hyperendemic for leprosy; the active search for cases, as well as the organization of health services, is an important method for disease control.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

AbstractLatent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

Sodium serum levels in hypoalbuminemic adults at general medical wards

Hypoalbuminemia may cause interstitial edema and hemodilution, which we hypothesized may influence serum sodium levels. Our purpose was to compare serum sodium levels of hospitalized adults with or without hypoalbuminemia. All sodium and albumin serum levels of 142 adults hospitalized at general medical wards over a six-month period were searched at a University Hospital mainframe computer. Relevant laboratory data and clinical details were also registered. Hypoalbuminemia was defined by serum albumin concentration < 3.3 g/dl Fisher, Mann-Whitney, and Student's t tests were applied to compare groups with or without hypoalbuminemia. Ninety-nine patients, classified as hypoalbuminemic, had lower blood hemoglobin (10.68 ± 2.62 vs. 13.54 ± 2.41), and sodium (135.1 ± 6.44 vs. 139.9 ± 4.76mEq/l) and albumin (2.74 ± 0.35 vs. 3.58 ± 0.28g/dl) serum levels than non-hypoalbuminemic (n=43). Pearson's coefficient showed a significant direct correlation between albumin and sodium serum levels (r=0.40) and between serum albumin and blood hemoglobin concentration (r=0.46). Our results suggest that hypoalbuminemic adults have lower serum sodium levels than those without hypoalbuminemia, a phenomenon that may be at least partially attributed to body water retention associated with acute phase response syndrome.

Prostate innervation and local anesthesia in prostate procedures

The nerve supply of the human prostate is very abundant, and knowledge of the anatomy contributes to successful administration of local anesthesia. However, the exact anatomy of extrinsic neuronal cell bodies of the autonomic and sensory innervation of the prostate is not clear, except in other animals. Branches of pelvic ganglia composed of pelvic (parasympathetic) and hypogastric (sympathetic) nerves innervate the prostate. The autonomic nervous system plays an important role in the growth, maturation, and secretory function of this gland. Prostate procedures under local anesthesia, such as transurethral prostatic resections or transrectal ultrasound-guided prostatic biopsy, are safe, simple, and effective. Local anesthesia can be feasible for many special conditions including uncomplicated prostate surgery and may be particularly useful for the high-risk group of patients for whom inhalation or spinal anesthesia is inadvisable.