Stigmatization of alcohol and other drug users by primary care providers in Southeast Brazil

This study reports on the views of Primary Health Care (PHC) providers in Southeast Brazil on the use of alcohol and other drugs which reflect stigma, moralization, or negative judgment. Six hundred nine PHC professionals from the Brazilian states of Sao Paulo and Minas Gerais took part in the study. The majority (86.5%) of these professionals were female. Attitudes toward the use of alcohol and other drugs were evaluated in comparison to Hansen`s disease, obesity, depression, schizophrenia. HIV/AIDS, and tobacco use. The use of tobacco, marijuana/cocaine, and alcohol were the most negatively judged behaviors (p < 0.05). Nursing assistants and community health care workers demonstrated the severest judgment of alcohol use. In addition, marijuana/cocaine addicts and alcoholics suffered the highest rate of rejection by professionals. The hypothesis that the use of alcohol and other drugs is a behavior stigmatized by health professionals being confirmed, it is important to develop strategies for changing provider attitudes in order to provide a higher quality of service to these patients. This study is important as a first study among PHC professionals about social stigma of alcohol and other drugs users. (C) 2009 Elsevier Ltd. All rights reserved.

Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces

Several neuropsychiatry disorders have shown a sexual dimorphism in their incidence, symptom profile and therapeutic response. A better understanding of the impact of sex hormones in emotional processing sexual dimorphism could bring tight to this important clinical finding. Some studies have provided evidence of sex differences in the identification of emotional faces, however, results are inconsistent and such inconsistency could be related to the lack of experimental control of the sex hormone status of participants. More recently, a few studies evaluated the modulation of facial emotion recognition by the phase of the menstrual cycle and sex hormones, however, none of them directly compared these results with a group of men. We evaluated the accuracy of facial emotion recognition in 40 healthy volunteers. Eleven women were assigned to early follicular group, nine women to the ovulatory group and 10 women to luteal group, depending on the phase of menstrual cycle, and a group of 10 men were also evaluated. Estrogen, progesterone and testosterone levels were assessed. The performance of the groups in the identification of emotional faces varied depending on the emotion. Early follicular group were more accurate to perceive angry faces than all other groups. Sadness was more accurately recognized by early follicular group than by luteal group and regarding the recognition of fearful faces a trend to a better performance and a significantly higher accuracy was observed, respectively, in the early follicular group and in the ovulatory group, in comparison to men. In women, estrogen negatively correlated to the accuracy in perception of angry mate faces. Our results indicate sex hormones to be implicated in a sexual dimorphism in facial emotion recognition, and highlight the importance of estrogen specifically in the recognition of negative emotions such as sadness, anger and fear. (C) 2009 Elsevier Ltd. All rights reserved.

Postural adjustment as a sign of attention in 7-month-old infants

Adjustments during postural control have been recognized in the process of the integration of movement and cognition. The objective of the present work was to describe postural changes and to verify if there is a correlation between postural adjustment and attention span in 7-month-old infants during 1 min of viewing an animated puppet. Method: Twenty-nine healthy infants (14 males) born from 31 to 39 weeks (median 36) were placed in a prone position and filmed watching a puppet during I min. The analysis of the images allowed us to catalogue the changes in position, the frequency of these changes, and the attention span. The following items were quantified: total number of infant positions, positions with weight transfer, changes in support, axis, decubitus, trunk and cervical movements, timing and pauses in visual attention. Results: Twenty-one infants stayed in the prone position during most of the recording, and eight chose sitting position before starting the session. Two groups were studied according to the main position throughout the filming, one in prone and the other in sitting positions, although they could rolling or crawling. For prone group the attention span was positively correlated with the number of positions with weight transfer (r = 0.53, p = 0.04), negatively correlated with trunk movements (r = -0.63, p = 0.01), and not correlated with birth or current weight. This work suggests that changes in the trunk movements and weight transfer are different traits related to the attention in 7-month-old infants. (C) 2008 Elsevier B.V.. All rights reserved.

Efficacy of cidofovir in recurrent juvenile respiratory papillomatosis

The efficacy of cidofovir in juvenile recurrent respiratory papillomatosis (JRRP) remains uncertain due to the lack of published case-control studies. Aim: To establish factors affecting the progression of JRRP prognosis, and to evaluate cidofovir for eradicating JRRP. Study Design: Retrospective. Methods: 22 children with JRRP were evaluated at a referral center. All children underwent surgical debulking, followed by cidofovir injection (Group 2) or not (Group 1). Age at diagnosis was correlated with the Derkay score and disease outcome. Disease progression was compared between groups 1 and 2. Results: fifteen children were considered disease-free; 8 were in Group 2 and 7 in Group 1. Age and total and clinical scores (P<0.05) were negatively correlated. The mean number of surgeries required to control the disease was identical in both groups; the duration of treatment until remission was significantly higher in Group 1 (P<0,05). Conclusion: JRRP is more aggressive in earlier onset disease. The duration of treatment was significantly lower in patients treated with cidofovir until eradication of JRRP compared to patients treated with surgery only.

Cigarette smoke exposure impairs respiratory epithelial ciliogenesis

Background: Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation. Methods: Monse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) Were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity. Results: CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 mu g/mL, yielding >70% nonciliation and shorter cilia compared With control. No statistical difference on transepithelial resistance was evident. Conclusion: CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduce the mucociliary clearance apparatuts after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.

Osteopontin expression according to molecular profile of invasive breast cancer: a clinicopathological and immunohistochemical study

Osteopontin (OPN) is a secreted, calcium-binding phosphorylated glycoprotein involved in several physiological and pathological events such as angiogenesis, apoptosis, inflammation, wound healing, vascular remodeling, calcification of mineralized tissues, and induction of cell proteases. There is growing interest in the role of OPN in breast cancer. In an attempt to obtain new insight into the pathogenesis of OPN-associated breast carcinomas, an immunohistochemical panel with 17 primary antibodies including cytokeratins and key regulators of the cell cycle was performed in 100 formalin-fixed paraffin-embedded samples of invasive breast carcinomas. OPN was expressed in 65% of tumors and was negatively correlated with estrogen (p=0.0350) and progesterone (p=0.0069) receptors, but not with the other markers and clinicopathological features evaluated including age, menstrual status, pathological grading, tumor size, and metastasis. There was no correlation between OPN expression and carcinomas of the basal-like phenotype (p=0.1615); however, OPN correlated positively with c-erbB-2 status (p=0.0286) and negatively with carcinomas of the luminal subtype (p=0.0353). It is well known that carcinomas overexpressing c-erbB-2 protein have a worse prognosis than luminal tumors. Here, we hypothesize that the differential expression of OPN in the first subtype of carcinomas may contribute to their more aggressive behavior. (Int J Biol Markers 2008; 23: 154-60)

The impact of perinatal and socioeconomic factors on mental health problems of children from a poor Brazilian city: a longitudinal study

Low birth weight and preterm birth, and social disadvantage may negatively affect mental health of children, but findings have been inconsistent. To assess the influence of perinatal and social factors on mental health problems in children aged 7-9 years. A random sample of 805 births in So Luis, Brazil was studied in 1997/1998 and again in 2005/2006. Perinatal, socioeconomic and demographic variables were assessed within 24 h after delivery. The Strengths and Difficulties Questionnaire (SDQ) was used to assess mental health problems in the children. Simple and multiple Poisson regressions were used for statistical analysis. The overall prevalence of mental health problems in the total sample was 47.7%. The prevalences of emotional and conduct problems were 58.2 and 48.8%, respectively. Only paternal age (< 20 years) was associated with mental health problems as measured by the full SDQ scale (prevalence ratio PR = 1.27). Children born to single mothers (PR = 1.31) and those with birth weight from 1,500 to 2,499 g (PR = 1.18) and from 2,500 to 2,999 g (PR = 1.17) had a higher risk of emotional problems, but those from low income families had a lower risk (PR = 0.80). Children with a father of less than 20 years had a higher risk of having problems with their peers (PR = 1.75). A maternal education of 9 years or over was inversely associated with peer (PR = 0.70) and conduct problems (PR = 0.73). Girls had a lower risk of conduct (PR = 0.77) and hyperactivity problems (PR = 0.68). A maternal education of 4 years or less increased the risk of hyperactivity (PR = 1.48). Socioeconomic and demographic conditions were better predictors of mental health problems in children than birth weight or preterm birth. However, since most effect sizes were small most mental health problems were, unexplained by the variables in the study.

Mineralocorticoid Receptor Mutations Differentially Affect Individual Gene Expression Profiles in Pseudohypoaldosteronism Type 1

Context: Type 1 pseudohypoaldosteronism (PHA1), a primary form of mineralocorticoid resistance, isdueto inactivating mutations of the NR3C2 gene, coding for the mineralocorticoid receptor (MR). Objective: The objective of the study was to assess whether different NR3C2 mutations have distinct effects on the pattern of MR-dependent transcriptional regulation of aldosterone-regulated genes. Design and Methods: Four MR mutations affecting residues in the ligand binding domain, identified in families with PHA1, were tested. MR proteins generated by site-directed mutagenesis were analyzed for their binding to aldosterone and were transiently transfected into renal cells to explore the functional effects on the transcriptional activity of the receptors by cis-trans-cotrans-activation assays and by measuring the induction of endogenous gene transcription. Results: Binding assays showed very low or absent aldosterone binding for mutants MR(877Pro), MR(848Pro), and MR(947stop) and decreased affinity for aldosterone of MR(843Pro). Compared with wildtype MR, the mutations p.Leu843Pro and p.Leu877Pro displayed half-maximal aldosterone-dependent transactivation of reporter genes driven by mouse mammary tumor virus or glucocorticoid response element-2 dependent promoters, whereas MR(848Pro) and MR(947stop) nearly or completely lost transcriptional activity. Although MR(848Pro) and MR(947stop) were also incapable of inducing aldosterone-dependent gene expression ofendogenoussgk1, GILZ, NDRG2, and SCNN1A, MR(843Pro) retained complete transcriptional activity on sgk1 and GILZ gene expression, and MR(877Pro) negatively affected the expression of sgk1, NDRG2, and SCNN1A. Conclusions: Our data demonstrate that MR mutations differentially affect individual gene expression in a promoter-dependent manner. Investigation of differential gene expression profiles in PHA1 may allow a better understanding of the molecular substrate of phenotypic variability and to elucidate pathogenic mechanisms underlying the disease. (J Clin Endocrinol Metab 96: E519-E527, 2011)

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate

Background: The major stress response to critical illness leads to a catabolic state and loss of lean body mass. Aims: To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. Design: Prospective observational study. Methods: Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clnicas, Faculty of Medicine of Ribeiro Preto, University of So Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. Results: Seventeen patients were studied for 310 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >= 1 g/kg/day and energy intake was >= 50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. Conclusions: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Tolerance to the cataleptic effect that follows repeated nitric oxide synthase inhibition may be related to functional enzymatic recovery

Systemic or intra-striatal acute administration of nitric oxide synthase (NOS) inhibitors causes catalepsy in rodents. This effect disappears after sub-chronic treatment. The aim of the present study was to investigate if this tolerance is related to changes in the expression of NOS or dopamine-2 (D(2)) receptor or to a recovery of NOS activity. Male albino Swiss mice (25-30 g) received single or sub-chronic (once a day for 4 days) i.p. injections of saline or L-nitro-arginine (L-NOARG, 40 mg/kg), a non-selective inhibitor of neuronal nitric oxide synthase (nNOS). Twenty-four hours after the last injection, the animals were killed and their brains were removed for immunohistochemistry assay to detect the presence of nNOS or for `in-situ` hybridisation study using (35)S-labeled oligonucleotide probe complementary to D(2) receptor mRNA. The results were analysed by computerised densitometry. Independent groups of animals received the same treatment, but were submitted to the catalepsy test and had their brain removed to measure nitrite and nitrate (NOx) concentrations in the striatum. Acute administration of L-NOARG caused catalepsy that disappeared after sub-chronic treatment. The levels of NOx were significantly reduced after acute L-NOARG treatment. The decrease in NOx after drug injection suffered a partial tolerance after sub-chronic treatment. The catalepsy time after acute or sub-chronic treatment with L-NOARG was negatively (r = -0.717) correlated with NOx levels. Animals that received repeated L-NOARG injections also showed an increase in the number of nNOS-positive neurons in the striatum. No change in D(2) receptor mRNA expression was found in the dorsal striatum, nucleus accumbens and substantia nigra. Together, these results suggest that tolerance to L-NOARG cataleptic effects do not depend on changes in D(2) receptors. They may depend, however, on plastic changes in nNOS neurons resulting in partial recovery of NO formation in the striatum.

Effects of intrapulpal temperature change induced by visible light units on the metabolism of odontoblast-like cells

Purpose: To investigate the effects of intrapulpal temperature changes induced by a quartz tungsten halogen (QTH) and a light emitting diode (LED) curing units on the metabolism of odontoblast-like cells. Methods: Thirty-six 0.5 mm-thick dentin discs obtained from sound human teeth were randomly assigned into three groups: QTH, LED and no light (control). After placement of the dentin discs in pulp chamber devices, a thermistor was attached to the pulpal surface of each disc and the light sources were applied on the occlusal surface. After registering the temperature change, odontoblast-like cells MDPC-23 were seeded on the pulpal side of the discs and the curing lights were again applied. Cell metabolism was evaluated by the MTT assay and cell morphology was assessed by SEM. Results: In groups QTH and LED the intrapulpal temperature increased by 6.4 degrees C and 3.4 degrees C, respectively. The difference between both groups was statistically significant (Mann-Whitney; P< 0.05). QTH and LED reduced the cell metabolism by 36.4% and 33.4%, respectively. Regarding the cell metabolism, no statistically significant difference was observed between both groups (Mann-Whitney; P> 0.05). However, when compared to the control, only QTH significantly reduced the cell metabolism (Mann-Whitney; P< 0.05). It was concluded that the irradiance of 0.5 mm-thick human dentin discs with a QTH in comparison to a LED curing unit promoted a higher temperature rise, which propagates through the dentin negatively affecting the metabolism of the underlying cultured pulp cells. (Am J Dent 2009;22:151-156).

Mechanisms of Action of Eicosapentaenoic Acid in Bladder Cancer Cells In Vitro: Alterations in Mitochondrial Metabolism, Reactive Oxygen Species Generation and Apoptosis Induction

Purpose: Eicosapentaenoic acid has been tested in bladder cancer as a synergistic cytotoxic agent in the form of meglumine-eicosapentaenoic acid, although its mechanism of action is poorly understood in this cancer. The current study analyzed the mechanisms by which eicosapentaenoic acid alters T24/83 human bladder cancer metabolism in vitro. Materials and Methods: T24/83 human bladder cancer cells were exposed to eicosapentaenoic acid for 6 to 24 hours in vitro and incorporation profiles were determined. Effects on membrane phospholipid incorporation, energy metabolism, mitochondrial activity, cell proliferation and apoptosis were analyzed Reactive oxygen species and lipid peroxide production were also determined. Results: Eicosapentaenoic acid was readily incorporated into membrane phospholipids with a considerable amount present in mitochondrial cardiolipin. Energy metabolism was significantly altered by eicosapentaenoic acid, accompanied by decreased mitochondrial membrane potential, and increased lipid peroxide and reactive oxygen species generation. Subsequently caspase-3 activation and apoptosis were detected in eicosapentaenoic acid exposed cells, leading to decreased cell numbers. Conclusions: These findings confirm that eicosapentaenoic acid is a potent cytotoxic agent in bladder cancer cells and provide important insight into the mechanisms by which eicosapentaenoic acid causes these changes. The changes in membrane composition that can occur with eicosapentaenoic acid likely contribute to the enhanced drug cytotoxicity reported previously in meglumine-eicosapentaenoic acid/epirubicin/mitomycin studies. Dietary manipulation of the cardiolipin fatty acid composition may provide an additional method for stimulating cell death in bladder cancer. In vivo studies using intravesical and dietary manipulation of fatty acid metabolism in bladder cancer merit further attention.

Is dystonic posturing during temporal lobe epileptic seizures the expression of an endogenous anticonvulsant system?

In temporal lobe epilepsy (TLE) seizures, tonic or clonic motor behaviors (TCB) are commonly associated with automatisms, versions, and vocalizations, and frequently occur during secondary generalization. Dystonias are a common finding and appear to be associated with automatisms and head deviation, but have never been directly linked to generalized tonic or clonic behaviors. The objective of the present study was to assess whether dystonias and TCB are coupled in the same seizure or are associated in an antagonistic and exclusive pattern. Ninety-one seizures in 55 patients with TLE due to mesial temporal sclerosis were analyzed. Only patients with postsurgical seizure outcome of Engel class I or II were included. Presence or absence of dystonia and secondary generalization was recorded. Occurrence of dystonia and occurrence of bilateral tonic or clonic behaviors were negatively correlated. Dystonia and TCB may be implicated in exclusive, non-coincidental, or even antagonistic effects or phenomena in TLE seizures. A neural network related to the expression of one behavioral response (e.g., basal ganglia activation and dystonia) might theoretically ""displace"" brain activation or disrupt the synchronism of another network implicated in pathological circuit reverberation and seizure expression. The involvement of basal ganglia in the blockade of convulsive seizures has long been observed in animal models. The question is: Do dystonia and underlying basal ganglia activation represent an attempt of the brain to block imminent secondary generalization? (C) 2007 Elsevier Inc. All rights reserved.

HLA-DRB1*1501 tagging rs3135388 polymorphism is not associated with neuromyelitis optica

Background: Association of the HLA-DRB1*1501 allele with multiple sclerosis is well established, but its association with neuromyelitis optica has only been evaluated in small populations. Methods: We performed a case-control genetic association study to evaluate the association of HLA-DRB1*1501 with neuromyelitis optica. The single nucleotide polymorphism rs3135388, which tags HLA-DRB1*1501, was genotyped in 164 patients with neuromyelitis optica, 220 patients with multiple sclerosis and 959 controls matched for age, gender and ethnicity. Genotyping for rs3135388 was performed by Taqman-based 5` nuclease assay. Results: Rs3135388*A was positively associated with multiple sclerosis (OR = 3.93; 95% CI = 2.58-5.97, p = 1.18 x 10(-09)) but negatively associated with NMO (OR = 0.57; 95% CI = 0.36-0.91, p = 0.01). Conclusions: Multiple sclerosis and neuromyelitis optica differ in their associations with DRB1*1501.

Evaluation of Leptospiral Recombinant Antigens MPL17 and MPL21 for Serological Diagnosis of Leptospirosis by Enzyme-Linked Immunosorbent Assays

Leptospirosis is a zoonosis of multisystem involvement caused by pathogenic strains of the genus Leptospira. In the last few years, intensive studies aimed at the development of a vaccine have provided important knowledge about the nature of the immunological mechanisms of the host. The purpose of this study was to analyze the immune responses to two recombinant proteins, MPL17 and MPL21 (encoded by the genes LIC10765 and LIC13131, respectively) of Leptospira interrogans serovar Copenhageni in individuals during infection. The recombinant proteins were expressed in Escherichia coli as six-His tag fusion proteins and were purified from the soluble bacterial fraction by affinity chromatography with Ni2+ -charged resin. The recombinant proteins were used to evaluate their ability to bind to immunoglobulin G (IgG) (and IgG subclass) or IgM antibodies in serum samples from patients in the early and convalescent phases of leptospirosis (n = 52) by enzyme-linked immunosorbent assays. The prevalences of total IgG antibodies against MPL17 and MPL21 were 38.5% and 21.2%, respectively. The titers achieved with MPL17 were statistically significantly higher than those obtained by the reference microscopic agglutination test. The specificity of the assay was estimated to be 95.5% for MPL17 and 80.6% for MPL21 when serum samples from individuals with unrelated febrile diseases and control healthy donors were tested. The proteins are conserved among Leptospira strains that cause human and animal diseases. MPL17 and MPL21 are most likely new surface proteins of leptospires, as revealed by liquid-phase immunofluorescence assays with living organisms. Our results demonstrate that these recombinant proteins are highly immunogenic and, when they are used together, might be useful as a means of diagnosing leptospirosis.