Relationship between obsessive-compulsive disorders and diseases affecting primarily the basal ganglia

Obsessive-compulsive disorder (OCD) has been reported in association with some neurological diseases that affect the basal ganglia such as Tourette's syndrome, Sydenham's chorea, Parkinson's disease, and Huntington's disease. Furthermore, studies such as neuroimaging, suggest a role of the basal ganglia in the pathophysiology of OCD. The aim of this paper is to describe the association of OCD and several neurologic disorders affecting the basal ganglia, report the existing evidences of the role of the basal ganglia in the pathophysiology of OCD, and analyze the mechanisms probably involved in this pathophysiology.

Necrolytic migratory erythema associated with glucagonoma syndrome: a case report

Necrolytic migratory erythema is a rare skin condition that consists of migrating areas of erythema with blisters that heal with hyperpigmentation. It usually occurs in patients with an alpha islet cell tumor of the pancreas-or glucagonoma-and when associated with glucose intolerance, anemia, hyperglucagonemia, and weight loss defines the glucagonoma syndrome. We describe a 52-year-old female patient with necrolytic migratory erythema associated with glucagonoma syndrome who had metastatic disease at presentation and passed away one week after her admission. The autopsy showed a tumor in the body of the pancreas, which was diagnosed as a neuroendocrine tumor and confirmed by immunohistochemistry. The diagnosis of necrolytic migratory erythema is a matter of great importance, since it might be an auxiliary tool for the early detection of glucagonoma.

Thumb metastasis from small cell lung cancer treated with radiation

A rare case of thumb metastasis from small cell lung cancer is presented. The patient underwent local radiotherapy with complete palliation of symptoms. She died 4 months later with disseminated disease. Considerations about incidence, treatment, and physiopathology of this kind of dissemination are made. Conservative treatment of finger metastasis with radiation may be considered due to the poor outcome of these patients.

Abnormal expression of CD54 in mixed reactions of mononuclear cells from hyper-IgE syndrome patients

Hyper-IgE syndrome (HIES) is a rare multisystem disorder characterized by increased susceptibility to infections associated with heterogeneous immunologic and non-immunologic abnormalities. Most patients consistently exhibit defective antigen-induced-T cell activation, that could be partly due to altered costimulation involving accessory molecules; however, the expression of these molecules has never been documented in HIES. Therefore, we investigated the expression of CD11a, CD28, CD40, CD54, CD80, CD86, and CD154 in peripheral blood mononuclear cells from six patients and six healthy controls by flow cytometry after autologous and mixed allogeneic reactions. Only the allogeneic stimuli induced significant proliferative responses and interleukin 2 and interferon gamma production in both groups. Most accessory molecules showed similar expression between patients and controls with the exception of CD54, being expressed at lower levels in HIES patients regardless of the type of stimulus used. Decreased expression of CD54 could partly explain the deficient T cell activation to specific recall antigens in HIES patients, and might be responsible for their higher susceptibility to infections with defined types of microorganisms.

Epithelial cell signaling responses to enterohemorrhagic Escherichia coli infection

Enterohemorrhagic Escherichia coli, including the serotype O157:H7 that is most commonly identified with human disease, cause both sporadic cases and outbreaks of non-bloody diarrhea and hemorrhagic colitis. In about 10% of infected subjects, the hemolytic uremic syndrome (hemolytic anemic, thrombocytopenia, and acute renal failure) develops, likely as a consequence of systemic spread of bacterial-derived toxins variously referred to as Shiga-like toxin, Shiga toxin, and Verotoxin. Increasing evidence points to a complex interplay between bacterial products - for example, adhesins and toxins - and host signal transduction pathways in mediating responses to infection. Identification of critical signaling pathways could result in the development of novel strategies for intervention to both prevent and treat this microbial infection in humans.

Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease

The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

Enhanced T cell activation in Plasmodium falciparum malaria-infected human immunodeficiency virus-1 patients from Mozambique

Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4+ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4+ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8+ and human leukocyte antigen-DR expression on CD3+ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Arterial hypertension and metabolic profile in patients with polycystic ovary syndrome

PURPOSE: To evaluate parameters related with arterial pressure and metabolic profile in women with polycystic ovary syndrome (POS). METHODS: This monocentric study at the University Hospital Endocrinology Section included 60 women aged 18-45 years, 42 being diagnosed with POS and acting as 18 controls. All women were subjected to transvaginal ultrasound and monitored for arterial pressure for 24 h in the ambulatory (MAP). Venous blood samples were taken between 07.00 and 09.00, after 12 h fasting. Basal (BG) and fasting glucose concentrations, total cholesterol and its fractions, triglycerides and insulin (to calculate the homeostatic assay insulin-resistance, HOMA-IR) were measured. Collected data were the mean arterial blood pressure (24-h awake/sleep cycle), arterial pressure nocturnal descensus, glycemia and fasting glucose for HOMA-IR, and lipid profile. The Student's t test was used to compare homogeneous variables; the Mann-Whitney test was used to compare non-homogeneous variables; the Pearson's correlation coefficient was used to search for correlation between the variables. The c² test was used for comparison of the absence of nocturnal descensus. Significance was taken as p<0.05. RESULTS: The mean age of the patients with POS was 27.4±5.5 (18-45 years, n=42) and the body mass index (BMI) was 30.2±6.5 kg/m² (18.3-54.9). In the Control Group, the mean age was 31.4±6.1 (18-45 years) and the BMI was 27.1±6.2 kg/m² (18.3-54.9, n=18). No difference in the metabolic parameters and insulin resistance was observed between the two groups. Comparison between these parameters and MAP showed that the only parameter with a correlation was the BMI, independent of the POS diagnosis. This was not seen in nocturnal descensus, which was uncorrelated with POS and any of the other studied parameters. CONCLUSION: POS women do not show higher arterial blood pressure, glycemia, HDL-col, TG, HOMA-IR and BMI compared to non-POS women. However, POS patients showed correlation between arterial pressure and BMI, suggesting that obesity is a primary factor involved in arterial pressure changes in these patients.

Association between Lipid Accumulation Product and Hirsutism in Patients with Polycystic Ovary Syndrome

Objective Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women between menarche and menopause. Clinical hyperandrogenism is the most important diagnostic criterion of the syndrome, which manifests as hirsutism in 70% of cases. Hirsute carriers of PCOS have high cardiovascular risk. Lipid accumulation product (LAP) is an index for the evaluation of lipid accumulation in adults and the prediction of cardiovascular risk. The aim of this study was to evaluate the association between LAP and hirsutism in women with PCOS. Methods This was a cross-sectional observational study of a secondary database, which included 263 patients who had visited the Hyperandrogenism Outpatient Clinic from November 2009 to July 2014. The exclusion criteria were patients without Ferriman-Gallwey index (FGI) and/or LAP data. We used the Rotterdam criteria for the diagnosis of PCOS. All patients underwent medical assessment followed by measurement and recording of anthropometric data and the laboratory tests for measurement of the following: thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, total testosterone, sex hormone binding globulin, 17-α-hydroxyprogesterone (follicular phase), glycohemoglobin A1c, and basal insulin. In addition, the subjects underwent lipid profiling and oral glucose tolerance tests. Other laboratory measurements were determined according to clinical criteria. LAP and the homeostatic model assessment index (HOMA-IR) were calculated using the data obtained. We divided patients into two groups: the PCOS group with normal LAP (< 34.5) and the PCOS group with altered LAP (> 34.5) to compare the occurrence of hirsutism. For statistical analysis, we used SPSS Statistics for Windows(r) and Microsoft Excel programs, with descriptive (frequencies, percentages, means, and standard deviations) and comparative analyses (Student's t-test and Chi-square test). We considered relations significant when the p-value was≤0.05. Results LAP was high in most patients (n = 177; 67.3%) and the FGI indicated that 58.5% of the patients (n = 154) had hirsutism. The analysis by LAP quartiles showed a positive correlation (p = 0.04) among patients with a high FGI and an upper quartile LAP (> 79.5) when compared with those with LAP < 29.0 (lower quartile). Conclusion This study demonstrated an association between high LAP and hirsutism. The FGI could represent a simple and low-cost tool to infer an increased cardiovascular risk in women with PCOS.

Intestinal lesions in pigs affected with postweaning multisystemic wasting syndrome

Samples of mesenteric lymph nodes and intestines from 79 unthrifty 3- to 5-month-old postweaning pigs, confirmed as naturally affected with postweaning multisystemic wasting syndrome (PMWS), were studied. Pigs originated from 12 farms in southern Brazil and were selected on the basis of clinical signs and/or gross lesions suggestive of enteric disorder. Lymphohistiocytic infiltrates of varying intensity were associated with anti-porcine circovirus type 2 (anti-PCV2) immunostaining (IS) in samples of intestines and mesenteric lymph nodes from all pigs. Although most findings were similar to those described in PCV2-associated enteritis, anti-PCV2 IS in association with depletion of the goblet cell mucin stores (24 pigs), diffuse ileal villous atrophy and fusion (18 pigs), and dilatation of the lymphatic vessels (11 pigs) combined or not with lymphangitis were also observed. PCV2 antigen was immunohistochemically demonstrated in the cytoplasm and nuclei from intralesional epithelial cells, histiocytes, and endothelial-like cells in intestinal tissues. Together these findings imply an association with PCV2. The presence of co-infections by Lawsonia intracellularis, Brachyspira spp., Mycobacterium spp., Salmonella spp., rotavirus, parvovirus, coronavirus and enteric calicivirus with PCV2 in the intestinal lesions was investigated.

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

The nucleolus: a paradigm for cell proliferation and aging

The nucleolus is the cellular site of ribosome biosynthesis. At this site, active ribosomal DNA (rDNA) genes are rapidly transcribed by RNA polymerase I (pol I) molecules. Recent advances in our understanding of the pol I transcription system have indicated that regulation of ribosomal RNA (rRNA) synthesis is a critical factor in cell growth. Importantly, the same signaling networks that control cell growth and proliferation and are deregulated in cancer appear to control pol I transcription. Therefore, the study of the biochemical basis for growth regulation of pol I transcription can provide basic information about the nuclear signaling network. Hopefully, this information may facilitate the search for drugs that can inhibit the growth of tumor cells by blocking pol I activation. In addition to its function in ribosome biogenesis, recent studies have revealed the prominent role of the nucleolus in cell senescence. These findings have stimulated a new wave of research on the functional relationship between the nucleolus and aging. The aim of this review is to provide an overview of some current topics in the area of nucleolus biology, and it has been written for a general readership.

Residual ß-cell function and microvascular complications in type 1 diabetic patients

To determine the influence of residual ß-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 ± 7.14 years, with a duration of diabetes of 9.1 ± 6.2 years. Forty-three patients (86%) with low C-peptide (<0.74 ng/ml) had longer duration of diabetes than 7 patients (14%) with high C-peptide (³0.74 ng/ml) (9 (2-34) vs 3 (1-10) years, P = 0.01) and a tendency to high glycated hemoglobin (HBA1) (8.8 (6-17.9) vs 7.7 (6.9-8.7)%, P = 0.08). Nine patients (18%) had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER) ³20 and <200 µg/min) and 13 (26%) had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 ± 0.5 vs 0.19 ± 0.22 ng/ml, P = 0.61) and between patients with or without retinopathy (0.4 ± 0.6 vs 0.2 ± 0.3 ng/ml, P = 0.43). Multiple regression analysis showed that duration of diabetes (r = 0.30, r2 = 0.09, P = 0.031) followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01) influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004). In our sample of type 1 diabetic patients residual ß-cell function was not associated with microalbuminuria or retinopathy.

Morphological changes of carotid bodies in acute respiratory distress syndrome: a morphometric study in humans

Carotid bodies are chemoreceptors sensitive to a fall of partial oxygen pressure in blood (hypoxia). The morphological alterations of these organs in patients with chronic obstructive pulmonary disease (COPD) and in people living at high altitude are well known. However, it is not known whether the histological profile of human carotid bodies is changed in acute clinical conditions such as acute respiratory distress syndrome (ARDS). The objective of the present study was to perform a quantitative analysis of the histology of carotid bodies collected from patients who died of ARDS. A morphometric study of carotid bodies collected during routine autopsies was carried out on three groups: patients that died of non-respiratory diseases (controls, N = 8), patients that presented COPD and died of its complications or associated diseases (N = 7), and patients that died of ARDS (N = 7). Morphometric measurements of the volume fraction of clusters of chief cells were performed in five fields on each slide at 40X magnification. The numerical proportion of the four main histological cell types (light, dark, progenitor and sustentacular cells) was determined analyzing 10 fields on each slide at 400X magnification. The proportion of dark cells was 0.22 in ARDS patients, 0.12 in controls (P<0.001), and 0.08 in the COPD group. The proportion of light cells was 0.33 (ARDS), 0.44 (controls) (P<0.001), and 0.36 (COPD). These findings suggest that chronic and acute hypoxia have different effects on the histology of glomic tissue.