CD1a and Factor XIIIa Immunohistochemistry in Leprosy: A Possible Role of Dendritic Cells in the Pathogenesis of Mycobacterium leprae Infection

Leprosy is a curable chronic granulomatous infectious disease caused by the bacillus Mycobacterium leprae. This organism has a high affinity for skin and peripheral nerve cells. In the evolution of infections, the immune status of patients determines the disease expression. Dendritic cells are antigen-presenting cells that phagocytose particles and microorganisms. In skin, dendritic cells are represented by epidermal Langerhans cells and dermal dendrocytes, which can be identified by expression of CD1a and factor XIIIa (FXIIIa). In the present study, 29 skin samples from patients with tuberculoid (13 biopsies) and lepromatous (16 biopsies) leprosy were analyzed by immunohistochemistry using antibodies to CD1a and FXIIIa. Quantitative analysis of labeling pattern showed a clear predominance of dendritic cells in tuberculoid leprosy. Difference between the number of positive cells of immunohistochemistry for the CD1a and FXIIIa staining observed in this study indicates a role for dendritic cells in the cutaneous response to leprosy. Dendritic cells may be a determinant of the course and clinical expression of the disease.

Exercise training inhibits inflammatory cytokines and more than prevents myocardial dysfunction in rats with sustained beta-adrenergic hyperactivity

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by beta-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-kappa B expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-kappa B expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-beta(1) mRNA. Thus, exercise training in a model of beta-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.

Prefrontal cortical and striatal activity to happy and fear faces in bipolar disorder is associated with comorbid substance abuse and eating disorder

Background: The spectrum approach was used to examine contributions of comorbid symptom dimensions of substance abuse and eating disorder to abnormal prefrontal-cortical and subcortical-striatal activity to happy and fear faces previously demonstrated in bipolar disorder (BD). Method: Fourteen remitted BD-type I and sixteen healthy individuals viewed neutral, mild and intense happy and fear faces in two event-related fMRI experiments. All individuals completed Substance-Use and Eating-Disorder Spectrum measures. Region-of-Interest analyses for bilateral prefrontal and subcortical-striatal regions were performed. Results: BD individuals scored significantly higher on these spectrum measures than healthy individuals (p<0.05), and were distinguished by activity in prefrontal and subcortical-striatal regions. BD relative to healthy individuals showed reduced dorsal prefrontal-cortical activity to all faces. Only BD individuals showed greater subcortical-striatal activity to happy and neutral faces. In BD individuals, negative correlations were shown between substance use severity and right PFC activity to intense happy faces (p<0.04), and between substance use severity and right caudate nucleus activity to neutral faces (p<0.03). Positive correlations were shown between eating disorder and right ventral putamen activity to intense happy (p<0.02) and neutral faces (p<0.03). Exploratory analyses revealed few significant relationships between illness variables and medication upon neural activity in BID individuals. Limitations: Small sample size of predominantly medicated BD individuals. Conclusion: This study is the first to report relationships between comorbid symptom dimensions of substance abuse and eating disorder and prefrontal-cortical and subcortical-striatal activity to facial expressions in BD. Our findings suggest that these comorbid features may contribute to observed patterns of functional abnormalities in neural systems underlying mood regulation in BD. (C) 2009 Elsevier B.V. All rights reserved.

Amygdala hyperactivation in untreated depressed individuals

The amygdala participates in the detection and control of affective states, and has been proposed to be a site of dysfunction in affective disorders. To assess amygdala processing in individuals with unipolar depression, we applied a functional MRI (fMRI) paradigm previously shown to be sensitive to amygdala function. Fourteen individuals with untreated DSM-IV major depression and 15 healthy subjects were studied using fMRI with a standardized emotion face recognition task. Voxel-level data sets were subjected to a multiple-regression analysis, and functionally defined regions of interest (ROI), including bilateral amygdala, were analyzed with MANOVA. Pearson correlation coefficients between amygdala activation and HAM-D score also were performed. While both depressed and healthy groups showed increased amygdala activity when viewing emotive faces compared to geometric shapes, patients with unipolar depression showed relatively more activity than healthy subjects, particularly on the left. Positive Pearson correlations between amygdala activation and HAM-D score were found for both left and right ROIs in the patient group. This study provides in vivo imaging evidence to support the hypothesis of abnormal amygdala functioning in depressed individuals. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Safety Profile of Trocar and Insufflation Needle Access Systems in Laparoscopic Surgery

BACKGROUND: The most common laparoscopic complications are associated with trocar insertion. The purpose of this study was to develop an objective method of evaluating the safety profile of various access devices used in laparoscopic surgery. STUDY DESIGN: In 20 swine, 6 bladed and 2 needle access devices were evaluated. A force profile was determined by measuring the force required to drive the trocar or needle through the fascia and into the peritoneum, at 0 and 10 mmHg. The amount Of tissue deformation, the length of blade exposed, and the duration of exposure were measured using a high-speed digital imaging system. RESULTS: The needle system without the sheath required the least driving force and had the most favorable force profile. In contrast, the bladed, nonretractable trocar system required a higher driving force and a rapid loss of resistance. Insertion under a pneumoperitoneum did not significantly alter the force profile of the various access devices except for the amount of tissue deformation. With the bladed system, the blade itself was exposed for an average of 0.5 to 1.0 seconds for a distance of 4.5 to 5.0 cm. In comparison, the needle system was exposed for 0.2 seconds for a distance of 1.8 cm. CONCLUSIONS: We developed a reproducible method of measuring the forces required to place the access systems, their pattern of resistance loss, and the characteristics of the blade exposure. These parameters may provide an adjunctive and objective measurement of safety, allowing for more direct comparison between various trocar designs. (J Am Coll Surg 2009;209:222-232. (C) 2009 by the American College of Surgeons)

The relationship between prevalent medial meniscal intrasubstance signal changes and incident medial meniscal tears in women over a 1-year period assessed with 3.0 T MRI

Objective Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period. Materials and methods A total of 161 women aged a parts per thousand yen40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher`s exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0). Results Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body. Conclusion We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period.

The Effect of Repetitive Pilot-Hole Use on the Insertion Torque and Pullout Strength of Vertebral System Screws

Study Design. In vitro biomechanical investigation of the screw-holding capacity. Objective. To evaluate the effect of repetitive screw-hole use on the insertional torque and retentive strength of vertebral system screws. Summary and Background Data. Placement and removal of vertebral system screws is sometimes necessary during the surgical procedures in order to assess the walls of the pilot hole. This procedure may compromise the holding capacity of the implant. Methods. Screws with outer diameter measuring 5, 6, and 7 mm were inserted into wood, polyurethane, polyethylene, and cancellous bone cylindrical blocks. The pilot holes were made with drills of a smaller, equal, or wider diameter than the inner screw diameter. Three experimental groups were established based on the number of insertions and reinsertions of the screws and subgroups were created according to the outer diameter of the screw and the diameter of the pilot hole used. Results. A reduction of screw-holding capacity was observed between the first and the following insertions regardless the anchorage material. The pattern of reduction of retentive strength was not similar to the pattern of torque reduction. The pullout strength was more pronounced between the first and the last insertions, while the torque decreased more proportionally from the first to the last insertions. Conclusion. Insertion and reinsertion of the screws of the vertebral fixation system used in the present study reduced the insertion torque and screw purchase.

Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors. (C) 2010 Elsevier B.V. All rights reserved.

Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naive Social Phobia Patients

Generalized Social Anxiety Disorder (SAD) is one of the most common anxiety conditions with impairment in social life. Cannabidiol (CBD), one major non-psychotomimetic compound of the cannabis sativa plant, has shown anxiolytic effects both in humans and in animals. This preliminary study aimed to compare the effects of a simulation public speaking test (SPST) on healthy control (HC) patients and treatment-naive SAD patients who received a single dose of CBD or placebo. A total of 24 never-treated patients with SAD were allocated to receive either CBD (600 mg; n = 12) or placebo (placebo; n = 12) in a double-blind randomized design 1 h and a half before the test. The same number of HC (n = 12) performed the SPST without receiving any medication. Each volunteer participated in only one experimental session in a double-blind procedure. Subjective ratings on the Visual Analogue Mood Scale (VAMS) and Negative Self-Statement scale (SSPS-N) and physiological measures (blood pressure, heart rate, and skin conductance) were measured at six different time points during the SPST. The results were submitted to a repeated-measures analysis of variance. Pretreatment with CBD significantly reduced anxiety, cognitive impairment and discomfort in their speech performance, and significantly decreased alert in their anticipatory speech. The placebo group presented higher anxiety, cognitive impairment, discomfort, and alert levels when compared with the control group as assessed with the VAMS. The SSPS-N scores evidenced significant increases during the testing of placebo group that was almost abolished in the CBD group. No significant differences were observed between CBD and HC in SSPS-N scores or in the cognitive impairment, discomfort, and alert factors of VAMS. The increase in anxiety induced by the SPST on subjects with SAD was reduced with the use of CBD, resulting in a similar response as the HC. Neuropsychopharmacology (2011) 36, 1219-1226; doi: 10.1038/npp.2011.6; published online 9 February 2011