Tuberculosis in Liver Transplant Recipients: Prophylaxis in an Endemic Area

AbstractBackgroundTuberculosis (TB) has a high prevalence in Brazil. The scenario of liver transplantation (LT) creates challenges: atypical presentation, treatment hepatotoxicity, and increased mortality. The majority of TB cases after transplantation represent reactivation of latent infections; therefore, prophylaxis (PX) plays a major role. The aim of this study was to evaluate the benefits of PX after LT based on a pretransplantation tuberculin test (TT) in an endemic area.MethodsRetrospective analysis of medical data from 376 adult cirrhotic patients undergoing OLT from 2001 to 2009.ResultsAmong 191 selected patients, 137 (71%) showed a pretransplant TT including 41 (30%) with a TT ≥5 mm. The 17 (40%) of these patients who were prescribed PX did not experience TB. Prophylaxis was discontinued in 5 patients (20%) owing to suspicion of hepatotoxicity (medium serum alanine transaminase 175 U/L). In the group without PX, we diagnosed 1 case of pulmonary TB. The overall prevalence of anergic patients in the cirrhotic phase was 65% and prevalence of TB 1%.ConclusionsThe prevalence of TB was similar to that reported in the literature, but positivity to TT was higher (34% vs 25%), possibly because of the endemicity of the area. There was a lower prevalence of extrapulmonary disease and no mortality. No patient undergoing PX with isoniazid, although incomplete due to suspicion of hepatotoxicity displayed TB. One patient without PX was affected by TB. The drug was effective but not always safe

Mephedrone (4-methylmethcathinone) and intracranial self-stimulation in C57BL/6J mice: Comparison to cocaine

The recreational use of cathinone-derived synthetic stimulants, also known as "bath salts", has increased during the last five years. A commonly abused drug in this class is mephedrone (4-methylmethcathinone or "meow-meow"), which alters mood and produces euphoria in humans. Intracranial self-stimulation (ICSS) measures the behavioral effects of neuroactive compounds on brain reward circuitry. We used ICSS to investigate the ability of mephedrone and cocaine to alter responding for electrical stimulation of the medial forebrain bundle in C57BL/6J mice. Adult male C57BL/6J mice (n=6) implanted with unipolar stimulating electrodes at the level of the lateral hypothalamus responded for varying frequencies of brain stimulation reward (BSR). The frequency that supported half maximal responding (EF50), the BSR threshold (θ(0)), and the maximum response rate were determined before and after intraperitoneal administration of saline, mephedrone (1.0, 3.0, or 10.0 mg/kg), or cocaine (1.0, 3.0, or 10.0 mg/kg). Mephedrone dose-dependently decreased EF50 (max. effect=72.3% of baseline), θ(0) (max. effect=59.6% of baseline), and the maximum response rate (max. effect=67.0% of baseline) beginning 15 min after administration. Beginning immediately after administration, cocaine dose-dependently lowered EF50 (max. effect=66.4% of baseline) and θ(0) (max. effect=60.1% of baseline) but did not affect maximum response rate. These results suggest that mephedrone, like cocaine, potentiates BSR, which may indicate its potential for abuse. Given the public health concern of stimulant abuse, future studies will be necessary to determine the cellular and behavioral effects of acute and chronic mephedrone use

Levetiracetam results in increased and decreased alcohol drinking with different access procedures in C57BL/6J mice

The antiepileptic, levetiracetam (LEV), has been investigated for the treatment of alcohol abuse. However, little is known about how LEV alters the behavioral effects of alcohol in laboratory animals. The acute effects of LEV on alcohol drinking by male C57BL/6J mice were investigated using two different drinking procedures, limited access (drinking-in-the-dark, or DID) and intermittent access (IA) drinking. In the first experiment (DID), mice had access to a single bottle containing alcohol or sucrose for four hours every-other day. In the second experiment (IA), mice had intermittent access to two bottles, one containing alcohol or sucrose and one containing water, for 24 h on Mon/Wed/Fri. In both experiments, mice were administered LEV (0.3 – 100 mg/kg i.p.) or vehicle 30 min before access to the drinking solutions. In the DID mice, LEV increased alcohol intake from 4.3 to 5.4 g/kg, while in the IA mice LEV decreased alcohol intake from 4.8 to 3.0 g/kg in the first 4 h of access and decreased 24 h alcohol intake from 20 g/kg to approximately 15 g/kg. These effects appear specific to alcohol, as LEV did not affect sucrose intake in either experiment. LEV appears to differentially affect drinking in animal models of moderate and heavier alcohol consumption

Generation of a CRF1-Cre transgenic rat and the role of central amygdala CRF1 cells in nociception and anxiety-like behavior

Corticotropin-releasing factor type-1 (CRF1) receptors are critical to stress responses because they allow neurons to respond to CRF released in response to stress. Our understanding of the precise role of CRF1-expressing neuronal populations in CRF-mediated behaviors has been largely limited to mouse experiments due to the lack of genetic tools available to selectively visualize and manipulate CRF1+ cells in rats. Here, we describe the generation and validation of a transgenic CRF1-Cre-tdTomato rat, which expresses a bicistronic iCre-2A-tdTomato transgene directed by 200kb of promoter and enhancer sequence surrounding the Crhr1 cDNA present within a BAC clone, that has been transgenically inserted into the rat genome. We report that Crhr1 and Cre mRNA expression are highly colocalized in CRF1-Cre-tdTomato rats within both the central amygdala (CeA), composed of mostly GABAergic neurons, and in the basolateral amygdala (BLA), composed of mostly glutamatergic neurons. In the CeA, membrane properties, inhibitory synaptic transmission, and responses to CRF bath application in tdTomato+ neurons are similar to those previously reported in GFP+ cells in CRFR1-GFP mice. We show that stimulatory DREADD receptors can be selectively targeted to CeA CRF1+ cells via virally delivered Cre-dependent transgenes, that transfected Cre/tdTomato+ cells are activated by clozapine-n-oxide in vitro and in vivo, and that activation of these cells in vivo increases anxiety-like behavior and nocifensive responses. Outside the amygdala, we show that Cre-tdTomato is expressed in several brain areas across the rostrocaudal axis of the CRF1-Cre-tdTomato rat brain, and that the expression pattern of Cre-tdTomato cells is similar to the known expression pattern of CRF1 cells. Given the accuracy of expression in the CRF1-Cre rat, modern genetic techniques used to investigate the anatomy, physiology, and behavioral function of CRF1+ neurons and circuits can now be performed in assays that require the use of rats as the model organism

Lymph node involvement in T1 non-small-cell lung cancer : could glucose uptake and maximal diameter be predictive criteria?

Objective: The introduction of modern staging systems such as computed tomography (CT) and positron emission tomography/CT (PET/CT) with fluorodeoxyglucose ([18F]FDG) has increased the detection of small peripheral lung cancers at an early stage. We analyzed the behavior of pathological T1 non-small-cell lung cancer (NSCLC) to identify criteria predictive of nodal involvement, and the role of cancer size in lymph node metastases. Methods: We retrospectively analyzed 219 patients with pathological T1 NSCLC. All patients were staged by high-resolution CT and PET as stage I, and underwent anatomical resection and radical lymphadenectomy. Our data were collected based on pathological nodule size (0-10mm; 11-20mm; and 21-30mm); morphological features of lung nodule and FDG uptake of the tumor measured by standardized uptake value (SUV). Results: A total of 190 patients (87%) were pN0, 14 (6%) pN1, and 15 (7%) pN2. No nodal involvement was observed in any of the 62 patients with nodule size less than 10mm, in 20 out of 120 patients (17%) with nodule size 11-20mm, and in nine out of 37 tumors (28%) 21-30mm in size (p=0.0007). All 55 patients with nodule SUV<2.0 and all 26 non-solid lesions were pN0 (respectively, p=0.0001 and p=0.03). All nodal metastases occurred among the group of 132 patients with size larger than 10mm and SUV higher than 2.0 with a 22% rate of nodal involvement of (29 patients) (p<0.0001). Conclusions: The low probability of lymph node involvement in NSCLC <1cm or showing glucose uptake <2 suggests lymphadenectomy could be avoided. A randomized trial should be performed to validate our data