Immunohistochemical evaluation of macrophage activity and its relationship with apoptotic cell death in the polar forms of leprosy

The objective of the present study was to investigate the correlation between macrophage activity and apoptosis in the polar forms of leprosy because the immunopathological phenomena involved in these forms are still poorly understood For this purpose, 29 skin biopsy samples obtained from patients with the polar forms of leprosy were analyzed. Macrophage activity and apoptosis were evaluated by immunohistochemistry using lysozyme, CD68, iNOS and caspase 3 as markers The nonparametric Mann-Whitney test and Spearman`s linear correlation test were used for statistical analysis The results suggest that the apoptosis rate is under the direct influence of macrophage activity in lesions of patients with the tuberculoid form In contrast, in lepromatous lesions other factors seem to induce programmed cell death, possibly TGF-beta. Further studies are necessary to identify additional factors involved in the immunopathogenesis of leprosy. (C) 2010 Elsevier Ltd. All rights reserved

Obstructive Sleep Apnea, Masked Hypertension, and Arterial Stiffness in Men

BACKGROUND Obstructive sleep apnea (OSA) is an established cause of hypertension However, it is not clear whether the frequency of masked hypertension in patients with OSA and whether OSA have an independent role on arterial stiffness taking into account ambulatory blood pressure (BP) monitoring (ABPM) METHODS We evaluated 61 male normotensive participants as determined by casual clinic BP level <140/90 mm Hg without clinical evidence of cardiovascular disease and on no medications (43 patients with moderate-to-severe OSA (apnea-hypopnea index (AHI) >= 15 events/hour by polysomnography) and 18 age- and body mass index-matched controls without OSA (AHl <5 events/hour)) Pulse wave velocity (PWV), an index of arterial stiffness, and 24-h ABPM were performed in a blinded fashion Masked hypertension was defined when abnormal daytime ABPM was >= 135 or >= 85 mm Hg RESULTS The AHI and lowest oxygen saturation were 26 +/- 16 and 90 +/- 2 vs 528 +/- 210 events/hour and 75 +/- 10% for controls and OSA patients, respectively, P < 0 001. Compared with controls, patients with OSA had higher office systolic BP (113 +/- 9 vs 118 +/- 10 mm Hg, P=0 05) and a higher unadjusted proportion of masked hypertension (2 controls (11.1%)vs 13 patients (30 2%), P < 005) PWV was 87 +/- 0.7, 9.4 +/- 1.0, and 10.6 +/- 1.1 m/s in the control, OSA without and with masked hypertension groups, respectively (P < 0 01 for each comparison) Multiple regression showed that systolic daytime ABPM and the lowest oxygen saturation were independently related to PWV (adjusted R(2) = 0 34, P < 0 01) CONCLUSIONS Patients with OSA presented a higher unadjusted rate of masked hypertension than matched controls. Lowest oxygen saturation has an independent association with arterial stiffness

Low DNA HTLV-2 proviral load among women in Sao Paulo city

Background: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HlV-1 co-infection. Methods: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. Results: Six of 53 HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 CopieS/10(4) PBMCs, p < 0.05). Conclusions: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus. (c) 2008 Elsevier B. V. All rights reserved.

Small Bowel Endoscopy Using the Double-Balloon Technique: Four-Year Results in a Tertiary Referral Hospital in Brazil

Background: Double-balloon enteroscopy (DBE) allows evaluation and therapy for various small bowel diseases. In this series the outcome of a 4-year experience in a tertiary hospital school in Brazil is reported. Methods: A total of 457 consecutive DBE were performed in 418 patients from August 2004 to August 2008. 93 patients with several indications, whose aim was not the evaluation of suspected diseases of the small bowel mucosa, were excluded, therefore leaving 364 DBE in 325 patients for analysis. Data were retrospectively collected with regard to clinical, endoscopic findings, therapy and complications. Results: Among the 364 DBE performed in 325 patients, 143/325 were males (44%) and 182/325 females (56%) with a mean age of 48.6 +/- 15.7 years (range 17-89). Mean investigation time was 64 +/- 22 min (range 35-135). The depth of insertion beyond the ligament of Treitz was 230 +/- 85 cm (range 30-500) by the antegrade approach and 140 +/- 75 cm (range 0-320) by the retrograde approach. Total enteroscopy was achieved in 41.66% of the attempts (30 of 72 patients). Overall diagnostic yield was 54.95% (200 of 364 procedures) ranging from 0 to 100% in this series, depending on the indication. Angiodysplasia was the main diagnosis in 24.5% (49 of 200 procedures) and endoscopic treatment, including biopsies, hemostasis, tattooing and polypectomy were performed in 65.38% (238 of 364 procedures). No major complications were reported. Conclusions: DBE is a feasible, safe and well-tolerated procedure allowing endoscopic therapy. Selection of indications increases its diagnostic yield. Copyright (C) 2009 S. Karger AG, Basel

Prevalence of cognitive and functional impairment in a community sample from Sao Paulo, Brazil

Aims: To present the prevalence of cognitive and functional impairment (CFI) in community-dwelling elderly subjects from the city of Sao Paulo. Methods: The population was aged 60 years and older (n = 1,563; 68.7% women and 31.3% men) and lived in different socioeconomic areas. The following instruments were administered to the elderly: the Mini Mental State Examination and the Fuld Object Memory Evaluation. The Informant Questionnaire on Cognitive Decline in the Elderly and the Bayer-Activities of Daily Living scale were administered to an informant. Results: The prevalence of CFI (n = 250) was 16% (95% confidence interval, CI: 14.2-17.8%) or 15.8% (95% CI: 13.8-17.8%). In regression models, the increase in the odds ratio (OR) of CFI was associated with age, for elderly individuals aged 75 years or older, illiterates or with 1-4 years of schooling, and with a history of stroke and diabetes mellitus. On the other hand, for subjects with a tumor history, the OR of CFI was significantly reduced. Conclusion: CFI was high and increased at older ages and in subjects with low education. Potentially changeable factors were identified (stroke and diabetes), and the possible `protective effect` of tumor/cancer against CFI should be further investigated by longitudinal studies. Copyright (C) 2007 S. Karger AG, Basel.

Experimental tuberculosis: Designing a better model to test vaccines against tuberculosis

Experimental models of infection are good tools for establishing immunological parameters that have an effect on the host-pathogen relationship and also for designing new vaccines and immune therapies. In this work, we evaluated the evolution of experimental tuberculosis in mice infected with increasing bacterial doses or via distinct routes. We showed that mice infected with low bacterial doses by the intratracheal route were able to develop a progressive infection that was proportional to the inoculum size. In the initial phase of disease, mice developed a specific Th1-driven immune response independent of inoculum concentration. However, in the late phase, mice infected with higher concentrations exhibited a mixed Th1/Th2 response, while mice infected with lower concentrations sustained the Th1 pattern. Significant IL-10 concentrations and a more preeminent T regulatory cell recruitment were also detected at 70 days post-infection with high bacterial doses. These results suggest that mice infected with higher concentrations of bacilli developed an immune response similar to the pattern described for human tuberculosis wherein patients with progressive tuberculosis exhibit a down modulation of IFN-gamma production accompanied by increased levels of IL-4. Thus, these data indicate that the experimental model is important in evaluating the protective efficacy of new vaccines and therapies against tuberculosis. (C) 2010 Elsevier Ltd. All rights reserved.

Angiotensin processing is partially carried out by carboxypeptidases in the rat mesenteric arterial bed perfusate

Here we investigated the possible association between the carboxypeptidase A (CPA)-like activity of the rat mesenteric arterial bed (MAB) perfusate and the ability of this fluid of forming angiotensin (Ang) 1-9 and Ang 1-7 upon incubation with Ang I and Ang II, respectively. Initially, we observed that anion exchange chromatography of the perfusate would consistently split the characteristic Z-Val-Phe-hydrolyzing activity of CPA-like enzymes into five distinct peaks, whose proteolytic activities were then determined using also Ang I and Ang II as substrates. The resulting proteolytic profile for each peak indicated that rat MAB perfusate contains a complex mixture of carboxypeptidases; tentatively, five carboxypeptidases were distinguished based on their substrate preferences toward Z-Val-Phe. Ang I and Ang II. The respective reactions, namely, Z-Val-Phe cleavage, Ang I to Ang 1-9 conversion and Ang II to Ang 1-7 conversion, were inhibited by 1,10-phenanthroline and nearly fully blocked by potato carboxypeptidase inhibitor. Also, all the CPA-like activity peaks prepared by anion exchange chromatography were tested negative for contaminating Ang I-converting enzyme-2, cathepsin A and prolylcarboxypeptidase. Overall, our results indicate that rat MAB perfusate contains a multiplicity of Ang I and Ang II-processing CPA-like enzymes whose proteolytic specificities suggest they might perform peculiar regulatory roles in the local resin-angiotensin system. (C) 2008 Elsevier B.V. All rights reserved.

Participation of kallikrein-kinin system in different pathologies

The general description of kinins refers to these peptides as molecules involved in vascular tone regulation and inflammation. Nevertheless, in the last years a series of, evidences has shown that local hormonal systems, such as the kallikrein-kinin system, may be differently regulated and are of pivotal importance to pathophysiological control. The combined interpretations of many recent studies allow us to conclude that the kallikrein-kinin system plays broader and richer roles than those classically described until recently. In this review, we report findings concerning the participation of the kallikrein-kinin system in inflammation, cancer, and in pathologies related to cardiovascular, renal and central nervous systems. (c) 2007 Elsevier B.V. All rights reserved.

Effects of time delay and transportation on isolation of pathogenic fungi from skin biopsies

BACKGROUND - It is not clear how culture media used during transport and the interval between the biopsy procedure and final processing can affect the successful isolation of fungi. OBJECTIVE - The aim of this study was to investigate the effects of late inoculation of skin biopsies, transported in different sterile fluids, on the isolation rate of pathogenic fungi. METHODS -A total of 278 punch biopsy specimens were collected from 47 patients with suspected lesions of invasive mycoses. Each biopsy was transported in vials with Sabouraud medium with chloramphenicol or saline solution and finally inoculated on Sabouraud agar and 2% chloramphenicol after a 48-72-hour (early) or after 72-hour-7-day (late) interval, comprising four groups of study. RESULTS - The medians of isolation rate of the four sporotrichosis groups were 100%. For paracoccidioidomycosis, the medians ranged from 50% to 84%, with no statistically significant difference among the groups (p=0.88). CONCLUSION - It was concluded that skin biopsies can be transported in Sabouraud medium or saline solution within a 7-day interval from specimen collection up to final inoculation, at room temperature, maintaining viability and growth rate of fungus in culture.

Dynamics of Parathyroid Hormone Secretion After Total Parathyroidectomy and Autotransplantation

Secondary hyperparathyroidism is a common complication in uremic patients. Total parathyroidectomy combined with partial autotransplantation into brachioradialis muscle has been the preference among the options for surgical treatment. This study was designed to evaluate the reserve and ability of suppression of autotransplanted parathyroid tissue using dynamics tests. We studied, prospectively, 12 patients in recent (RP) and late (LP) postoperative of total parathyroidectomy with autotransplantation. For analysis of the secretory reserve capacity, we induced hypocalcemia by ethylenediaminetetraacetic acid (EDTA) infusion. Furthermore, for analysis of the ability for parathyroid hormone (PTH) suppression, the hypercalcemia test was used, by intravenous administration of calcium in LP. In RP, there was a decrease in the average serum levels of PTH, phosphorus, and alkaline phosphatase, which ranged from 13 to 231 (87 +/- A 65) pg/ml, 2.3 to 6.2 (3.3 +/- A 1.1) mg/dl, and 77 to 504 (250 +/- A 135) U/L, respectively, similar to that observed in LP. The analysis of the average curve of variations in PTH during testing of the stimulus with EDTA showed lack of secretion in RP and partial response in LP. Impaired suppression ability of the graft in LP was observed in the test with intravenous calcium. Total parathyroidectomy followed by partial autotransplantation was effective in reducing PTH serum levels in patients with terminal kidney disease. The elevation of serum calcium during the suppression test was not able to inhibit the autograft gland secretion of PTH. The assessment of parathyroid graft function demonstrated an inability to respond to the stimulus of hypocalcemia induced by EDTA, although there was a partial recovery, in late postoperative period.

Liver mitochondrial function in familial amyloidotic polyneuropathy

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February `2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P <.05); 14 +/- 3 vs 17 +/- 7 nat.O/min/ mg.prot.mit. (P >.05); 3.6+/- .5 vs 1.7 +/- 0.7 (P <.05); and 135 +/- 5.2 vs 135 +/- 6 mV (P >.05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.

Elongated styloid process and atheroma in panoramic radiography and its relationship with systemic osteoporosis and osteopenia

Association between the presence of an elongated styloid process, vascular calcification (atheroma) and the potential risk factor for osteoporosis was studied. Presence of an elongated styloid process was found to be correlated with systemic osteoporosis and also between elongated styloid process and atheroma. The association between the presences of an elongated styloid process and vascular calcification (atheroma) with the potential risk factor assessment for osteoporosis was studied. Bone mineral density obtained by dual energy X-ray absorptiometry diagnosed osteopenia/osteoporosis on at least two of three sites (column, hips, and forearm) of 50 female patients. Panoramic maxillomandibular radiographs were taken and analyzed. Elongation of the styloid processes was measured and the presence of atheromas in the carotid was investigated. Eighty percent of the patients presented at least one side with elongated styloid process and the highest prevalence (87.5%) occurred in individuals between 60 and 69 years. Atheroma was found in four patients, three of which presented elongated styloid on at least one side and had diagnosed osteoporosis on at least two of the evaluated sites. Correlation was found between the elongation of the styloid process and systemic osteoporosis, and between elongated styloid process and atheroma. The method in this study might be used as part of a method for osteopenia/osteoporosis and atheroma risk assessment.

Screening of autosomal gene deletions in patients with hypogonadotropic hypogonadism using multiplex ligation-dependent probe amplification: detection of a hemizygosis for the fibroblast growth factor receptor 1

P>Objective Congenital hypogonadotropic hypogonadism with anosmia (Kallmann syndrome) or with normal sense of smell is a heterogeneous genetic disorder caused by defects in the synthesis, secretion and action of gonadotrophin-releasing hormone (GnRH). Mutations involving autosomal genes have been identified in approximately 30% of all cases of hypogonadotropic hypogonadism. However, most studies that screened patients with hypogonadotropic hypogonadism for gene mutations did not include gene dosage methodologies. Therefore, it remains to be determined whether patients without detected point mutation carried a heterozygous deletion of one or more exons. Measurements We used the multiplex ligation-dependent probe amplification (MLPA) assay to evaluate the potential contribution of heterozygous deletions of FGFR1, GnRH1, GnRHR, GPR54 and NELF genes in the aetiology of GnRH deficiency. Patients We studied a mutation-negative cohort of 135 patients, 80 with Kallmann syndrome and 55 with normosmic hypogonadotropic hypogonadism. Results One large heterozygous deletion involving all FGFR1 exons was identified in a female patient with sporadic normosmic hypogonadotropic hypogonadism and mild dimorphisms as ogival palate and cavus foot. FGFR1 hemizygosity was confirmed by gene dosage with comparative multiplex and real-time PCRs. Conclusions FGFR1 or other autosomal gene deletion is a possible but very rare event and does not account for a significant number of sporadic or inherited cases of isolated GnRH deficiency.

Dual role of hydrogen sulfide in mechanical inflammatory hypernociception

Hydrogen Sulfide (H2S) is an endogenous gas involved in several biological functions, including modulation of nociception. However, the mechanisms involved in such modulation are not fully elucidated. The present Study demonstrated that the pretreatment of mice with PAG, a H2S synthesis inhibitor, reduced LPS-induced mechanical paw hypernociception. This inhibition of hypernociception was associated with the prevention of neutrophil recruitment to the plantar tissue. Conversely, PAG had no effect on LPS-induced production of the hypernociceptive cytokines, TNF-alpha, IL-1 beta and CXCL1/KC and on hypernociception induced by PGE(2), a directly acting hypernociceptive mediator. In contrast with the pro-nociceptive role of endogenous H2S. systemic administration of NaHS, a H2S donor, reduced LPS-induced mechanical hypernociception in mice. Moreover, this treatment inhibited mechanical hypernociception induced by PGE(2), suggesting a direct effect of H2S on nociceptive neurons. The antinociceptive mechanism of exogenous H2S depends on K-(ATP)(+) channels since the inhibition of PGE(2) hypernociception by NaHS was prevented by glibenclamide (K-(ATP)(+) channel blocker). Finally, NaHS did not alter the thermal nociceptive threshold in the hot-plate test, confirming that its effect is mainly peripheral. Taken together, these results suggest that H2S has a dual role in inflammatory hypernociception: 1. an endogenous pro-nociceptive effect due to up-regulation of neutrophil migration. and 2. an antinociceptive effect by direct blockade of nociceptor sensitization modulating K-(ATP)(+) channels. (c) 2008 Elsevier B.V. All rights reserved.

Brachial artery pulsatility index change 1 minute after 5-minute forearm compression - Comparison with flow-mediated dilatation

Objective. Endothelial impairment evaluation by sonographic measurement of flow-mediated dilatation (FMD) has become broadly used. However, this method has 2 main caveats: the dilatation depends on the baseline arterial diameter, and a high precision level is required. Vasodilatation leads to an amplified fall in impedance. We hypothesized that assessment of the pulsatility index change (PI-C) 1 minute after 5-minute forearm compression might evaluate that fall in impedance. The aim of this study was to compare the PI-C with FMD. Methods. Flow-mediated dilatation and the PI-C were assessed in 51 healthy women aged between 35.1 and 67.1 years. We correlated both FMD and the PI-C with age, body mass index, waist circumference, cholesterol level, high-density lipoprotein level, glucose level, systolic and diastolic blood pressure, pulse pressure, brachial artery diameter, simplified Framingham score, intima-media thickness, and carotid stiffness index. Intraclass correlation coefficients between 2 FMD and PI-C measurements were also examined. Results. Only FMD correlated with baseline brachial diameter (r=-0.53). The PI-C had a high correlation with age, body mass index, waist circumference, cholesterol level, systolic blood pressure, pulse pressure, simplified Framingham score, and intima-media thickness. The correlation between FMD and the PI-C was high (r=-0.66). The PI-C had a higher intraclass correlation coefficient (0.991) than FMD (0.836) but not brachial artery diameter (0.989). Conclusions. The PI-C had a large correlation with various markers of cardiovascular risk. Additionally, PI-C measurement does not require offline analysis, extra software, or electrocardiography We think that the PI-C could be considered a marker of endothelial function. However, more studies are required before further conclusions.