Excessive Checking in Obsessive-Compulsive Disorder: Neurochemical Correlates Revealed by 7T Magnetic Resonance Spectroscopy.

Background: Compulsive checking, a common symptom of obsessive-compulsive disorder (OCD), has been difficult to capture experimentally. Therefore, determination of its neural basis remains challenging despite some evidence suggesting that it is linked to dysfunction of cingulostriatal systems. This study introduces a novel experimental paradigm to measure excessive checking and its neurochemical correlates. Methods: Thirty-one patients with OCD and 29 healthy volunteers performed a decision-making task requiring them to decide whether 2 perceptually similar visual representations were the same or different under a high-uncertainty condition without feedback. Both groups underwent 7T magnetic resonance spectroscopy scans on the same day. Correlations between out-of-scanner experimental measures of checking and the glutamate/GABA (gamma-aminobutyric acid) ratio in the anterior cingulate cortex, supplementary motor area, and occipital cortex were assessed. Their relationship with subjective ratings of doubt, anxiety, and confidence was also investigated. Results: Patients with OCD exhibited excessive and dysfunctional checking, which was significantly correlated with changes in the glutamate/GABA ratio within the anterior cingulate cortex. No behavioral/neurochemical relationships were evident for either the supplementary motor area or occipital cortex. The excessive checking observed in patients was negatively correlated with their confidence levels and positively related to doubt, anxiety, and compulsivity traits. Conclusions: We conclude that experimental measures of excessive and dysfunctional checking in OCD, which have been linked to increased doubt, anxiety, and lack of confidence, are related to an imbalance between excitatory and inhibitory neural activity within the anterior cingulate cortex. This study adds to our understanding of the role of this region in OCD by providing a laboratory model of the possible development of compulsive checking.

Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

Gingival Pigmentation Removal With a High-Power Diode Laser in Non-contact Mode: A Proposed Technique With Two Years of Follow-Up.

This case report describes the efficacy and advantages of using a high-power diode laser in non-contact mode to remove racial melanin pigmentation from the oral mucosa in an aesthetically sensible area to reduce thermal damage and promote better postoperative results. In the presented case, the lesion was removed under local anesthesia in a single session using high-power diode equipment with circular movements over the lesion (10 seconds maximum for each irradiation cycle, with 30 seconds for thermal relaxation, for a total of two cycles), maintaining an average distance of 2-3 mm from the target tissue without fiber activation (continuous wave, 2 W, delivered by quartz fiber with 300 µ). The patient did not report immediate postoperative pain; however, analgesic use was recorded during the first day after the surgical procedure. The biological response and cosmetic results were satisfactory, with proper lesion removal and adequate cicatrization observed during a two-year follow-up period, without complications or compromise of periodontal tissue esthetics.

Electroencephalographic Correlates of Obsessive-Compulsive Disorder.

This chapter reviews EEG research in Obsessive-Compulsive Disorder (OCD), focusing on Event-Related Potentials (ERPs) such as the Contingent Negative Variation, N2, Error-Related Negativity, the feedback Error-Related Negativity and the Readiness Potential and their neural bases. The functional significance, utility and correlation of these ERPs with OCD symptoms will be discussed, alongside novel theories for integrating the research findings. I will consider hypotheses including goal-directed behaviour, overreliance on habits, dissociations between action and knowledge, and excessive intolerance of uncertainty in the context of EEG studies, thus providing a comprehensive framework of the electroencephalographic literature concerning OCD.

Are candidate neurocognitive endophenotypes of OCD present in paediatric patients? A systematic review.

To-date it has been difficult to ascertain the exact cognitive profile of childhood OCD as studies report variable results. Adult OCD research lately utilises the endophenotype approach; studying cognitive traits that are present in both patients and their unaffected first-degree relatives, and are thought to lie closer to the genotype than the full-blown disorder. By observing whether candidate endopenotypes of adult OCD are present in child patients, we can determine whether the two subtypes show cognitive overlap. We conducted a systematic review of the paediatric OCD literature focussing on proposed neurocognitive endophenotypes of OCD: cognitive flexibility, response inhibition, memory, planning, decision-making, action monitoring, and reversal learning. We found that paediatric patients present robust increases in brain error related negativity associated with abnormal action monitoring, impaired decision-making under uncertainty, planning, and visual working memory, but there is less evidence for deficits in other cognitive domains. This implies that children with OCD show some cognitive similarities with adult patients, but other dysfunctions may only manifest later in the disorder trajectory.

The impact of photobiomodulation on osteoblast-like cell: a review.

In this study, we present a review of the literature on the impact of photobiomodulation on osteoblast-like cell culture. Searches were performed in the PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), SCOPUS, and SPIE digital library databases for original articles regarding the effects of LLLT on osteoblast-like cells in experimental models using LLLT published in English from the last 20 years. The search identified 1439 studies. After the analysis of the abstracts, 1409 studies were excluded and 30 studies were then selected for the full-text analysis, 8 of which were excluded. Thus, 22 studies were included for a critical evaluation of the impact of photobiomodulation on osteoblast-like cell culture. The cell lineages studied were primary rat, primary human, saos-2, Osteo-1, MC3T3, MG63, and OFCOL II. Moreover, a wide variety of experimental models were used to experimentally analyze the impact of photobiomodulation, the most common of which were alkaline phosphatase, MTT, and cell count. This review suggests that osteoblastic-like cells are susceptible to photobiomodulation but that most of the light parameters varied by different authors have little to no influence on proliferation but very high levels of irradiance have demonstrated deleterious effects on proliferation, highlighting the bi-phasic effect of photobiomodulation.

Experimental Lachesis muta rhombeata envenomation and effects of soursop (Annona muricata) as natural antivenom.

BACKGROUND: In the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata. METHODS: We evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment. RESULTS: LmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV. CONCLUSION: The treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.

Apoptosis-related gene expression profile in chronic myeloid leukemia patients after imatinib mesylate and dasatinib therapy.

BACKGROUND/AIMS: We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients. METHODS: Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR. RESULTS: Anti-apoptotic genes (c-FLIP and MCL-1) were overexpressed and the pro-apoptotic BIK was reduced in CML patients. Expression of BMF, A1, c-FLIP, MCL-1, CIAP-2 and CIAP-1 was modulated by DAS. In IM-resistant patients, expression of A1, c-FLIP, CIAP-1 and MCL-1 was upregulated, and BCL-2, CIAP-2, BAK, BAX, BIK and FASL expression was downregulated. CONCLUSION: Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM.

Altered erythropoiesis and iron metabolism in carriers of thalassemia.

The thalassemia syndromes (α- and ß-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or ß-globin chain production results in impaired red blood cell synthesis, anemia, and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis, and dysfunctional iron metabolism has not been investigated in both α-thalassemia carriers (ATC) and ß-thalassemia carriers (BTC). Here, we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changes in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferritin and (hepcidin/ferritin)/sTfR are, respectively, increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis.

Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis.

BACKGROUND: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34+ hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters. RESULTS: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34+ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34+ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly. CONCLUSIONS: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.

Phagocytosis and nitric oxide levels in rheumatic inflammatory states in elderly women.

BACKGROUND: Very few studies have investigated, in the elderly, the effect of rheumatic inflammatory states on phagocyte function and free radical production. The objective of this article is to evaluate phagocytosis by neutrophils and the production of nitric oxide (·NO) by monocytes in elderly women recruited among patients of the Brazilian Public Health System. METHODS: Forty patients aged more than 60 years with rheumatic inflammatory diseases were studied. Phagocytosis was measured by flow cytometry. ·NO production was measured by the total nitrite assay and conventional inflammation markers were determined. Data were analyzed with the Mann-Whitney nonparametric test and P<0.05 was considered significant. RESULTS: C-reactive protein levels and white blood cell counts were significantly higher in inflammation than in the control group (P<0.05). The phagocytosis fluorescence intensity per neutrophil and the percentual of neutrophils expressing phagocytosis were significantly higher (P<0.05) in the test than in the control group. Furthermore, there was significant ·NO overproduction by monocytes, (P<0.05). CONCLUSION: Phagocytosis and ·NO production are affected by rheumatic states. This suggests that the increased ·NO levels may play a part in the increased oxidative stress in rheumatic diseases in elderly women.

Differential expression of apoptosis-related genes from death receptor pathway in chronic myeloproliferative diseases.

BACKGROUND: Chronic myeloproliferative disorders (MPDs) are clonal haematopoietic stem cell malignancies characterised by an accumulation of mature myeloid cells in bone marrow and peripheral blood. Deregulation of the apoptotic machinery may be associated with MPD physiopathology. AIMS: To evaluate expression of death receptors' family members, mononuclear cell apoptosis resistance, and JAK2 allele burden. SUBJECTS AND METHODS: Bone marrow haematopoietic progenitor CD34 cells were separated using the Ficoll-hypaque protocol followed by the Miltenyi CD34 isolation kit, and peripheral blood leukocytes were separated by the Haes-Steril method. Total RNA was extracted by the Trizol method, the High Capacity Kit was used to synthesise cDNA, and real-time PCR was performed using SybrGreen in ABIPrism 7500 equipment. The results of gene expression quantification are given as 2(-ΔΔCt). The JAK2 V617F mutation was detected by real-time allelic discrimination PCR assay. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-hypaque protocol and cultured in the presence of apoptosis inducers. RESULTS: In CD34 cells, there was mRNA overexpression for fas, faim and c-flip in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), as well as fasl in PMF, and dr4 levels were increased in ET. In leukocytes, fas, c-flip and trail levels were increased in PV, and dr5 expression was decreased in ET. There was an association between dr5 and fasl expression and JAK2V617F mutation. PBMCs from patients with PV, ET or PMF showed resistance to apoptosis inducers. CONCLUSIONS: The results indicate deregulation of apoptosis gene expression, which may be associated with MPD pathogenesis leading to accumulation of myeloid cells in MPDs.

[Scenario of the service to damage provoked by accidents and violence against elderly at SUS in Manaus (AM, Brazil)]. / Cenário do atendimento aos agravos provocados por acidentes e violência contra idosos na rede SUS de Manaus (AM, Brasil).

The aim of this article is to describe the public service of Manaus to elderly, either victims of accidents or violence, on three levels of service (32 pre-hospital, 5 hospital and 5 rehabilitation). It is a descriptive study with a quantitative and qualitative approach, where 42 health units were investigated. The results reveal that the emergency services department presents a better physical structure. The organization concerning these matters is still incipient in Manaus. It was detected scarcity in the number of hospital beds and vacancies in the intensive care unit to offer the continuity of the treatment. There's a need for professional qualifications and medical specialties to attend elderly admitted due to injury. Very little has been done in the prevention area. Data entry and notification appear as one of the weakest points on the three levels of attention. The most critical point is related to hospitalization, being this level of attention largely mentioned by managers and health professionals as in great need for re-structuring.

Whole blood, serum, and saliva lead concentrations in 6- to 8-year-old children.

With increasing evidence of adverse health effects of lower lead levels (below 10microg/dL in whole blood), studies on novel internal dose biomarkers are needed. This study aimed at: (1) assessing the lead exposure by measuring this element in whole blood (Pb-blood), serum (Pb-serum), and 3 different types of saliva: whole (Pb-whole-saliva), submandibular/sublingual (Pb-sub-saliva) and parotid saliva (Pb-parotid-saliva); (2) correlating Pb-blood with Pb-serum; and (3) relating Pb-blood and Pb-serum with the lead found in the different salivas. The study population included 444 children aged 6 to 8 years attending 4 government schools in the district of Campos Eliseos, in Ribeirao Preto, Sao Paulo State, Brazil. Whole blood, serum, parotid, submandibular/sublingual ("sub-saliva"), and whole saliva were collected in trace element-free tubes. Lead concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Median Pb-blood and Pb-serum were 2.1microg/dL and 0.4microg/L, respectively. Ten percent of the children had Pb-blood between 4.0 and 9.4microg/dL. Boys showed higher Pb-blood than girls (2.3 vs. 2.0microg/dL, p<0.0003). Lead concentrations in whole, sub, and parotid saliva were 1.7, 1.4, and 1.3microg/L, respectively. No significant correlations were found between Pb-blood and Pb-serum, between Pb-blood and lead in the 3 different salivas, or between Pb-serum and Pb-whole-saliva or Pb-sub-saliva. However, there was a weak statistically significant correlation between Pb-serum and Pb-parotid-saliva. In conclusion, the mean Pb-blood concentration was 2.4microg/dL, with 10% of the children exhibiting Pb-blood between 4.0 and 9.4microg/dL. Boys presented higher Pb-blood. Results suggest that Pb-blood has no correlation with Pb-serum or lead in the 3 different salivas collected here. A weak but statistically significant correlation between Pb-serum and Pb-parotid-saliva was found. Our results also point to the need for carrying out more studies on sources of exposure and lead levels in children in Brazil.

O pioneirismo de Louis Le Guillant na reforma psiquiátrica e psicoterapia institucional na França: a importância do trabalho dos pacientes para a abertura dos hospícios / The pioneering spirit of Louis Le Guillant on Psychiatric Reform and Institutional Psychotherapy in France: the importance of the work of patients for the opening of the hospices

O artigo apresenta elementos da vida e da obra do psiquiatra francês Louis Le Guillant relativos às suas contribuições no campo da nascente Psicoterapia Institucional / Reforma Psiquiátrica na França, em particular nas décadas de 1940 e 1950. O método baseou-se em busca exaustiva da produção escrita de Le Guillant, de seus críticos, de psiquiatras próximos a ele e da geração seguinte, analisando cada um dos textos referidos, cruzando as informações entre si e, sempre que necessário, com a história da França e internacional no século XX. Demonstra que ele exerceu uma prática e levantou questões teóricas que podem ajudar a compreender problemas que se enfrentam hoje na Reforma Psiquiátrica brasileira, no que diz respeito a temas como saúde, trabalho, moradia, organização, entre outros. Deste modo, este artigo busca colaborar para conhecer parte da riqueza da obra deste autor, insuficientemente conhecido

This article presents elements of life and work of French psychiatrist Louis Le Guillant for their contributions in the field of young institutional psychotherapy / Psychiatric Reform in France, particularly in the 1940s and 1950s. The method was based on exhaustive search of the written production of Le Guillant, its critics, of psychiatrists coming to him and the next generation, examining each of these texts, crossing the information among themselves and, where necessary, with the history of the France and the international in the twentieth century. Shows that he had a practical and theoretical issues raised that can help understand on problems that are facing today in the Brazilian Psychiatric Reform, regarding issues such as health, work, housing, organization, among others. Thus, this paper works to know that wealth of works by this author are insufficiently known

O pioneirismo de Louis Le Guillant na reforma psiquiátrica e psicoterapia institucional na França: a importância do trabalho dos pacientes para a abertura dos hospícios / The pioneering spirit of Louis Le Guillant on Psychiatric Reform and Institutional Psychotherapy in France: the importance of the work of patients for the opening of the hospices

O artigo apresenta elementos da vida e da obra do psiquiatra francês Louis Le Guillant relativos às suas contribuições no campo da nascente Psicoterapia Institucional / Reforma Psiquiátrica na França, em particular nas décadas de 1940 e 1950. O método baseou-se em busca exaustiva da produção escrita de Le Guillant, de seus críticos, de psiquiatras próximos a ele e da geração seguinte, analisando cada um dos textos referidos, cruzando as informações entre si e, sempre que necessário, com a história da França e internacional no século XX. Demonstra que ele exerceu uma prática e levantou questões teóricas que podem ajudar a compreender problemas que se enfrentam hoje na Reforma Psiquiátrica brasileira, no que diz respeito a temas como saúde, trabalho, moradia, organização, entre outros. Deste modo, este artigo busca colaborar para conhecer parte da riqueza da obra deste autor, insuficientemente conhecido.(AU)

This article presents elements of life and work of French psychiatrist Louis Le Guillant for their contributions in the field of young institutional psychotherapy / Psychiatric Reform in France, particularly in the 1940s and 1950s. The method was based on exhaustive search of the written production of Le Guillant, its critics, of psychiatrists coming to him and the next generation, examining each of these texts, crossing the information among themselves and, where necessary, with the history of the France and the international in the twentieth century. Shows that he had a practical and theoretical issues raised that can help understand on problems that are facing today in the Brazilian Psychiatric Reform, regarding issues such as health, work, housing, organization, among others. Thus, this paper works to know that wealth of works by this author are insufficiently known.(AU)

Regulação sanitária por um enfoque judicial: o horário de funcionamento de farmácias e drogarias no estado de São Paulo / Sanitary regulation for a judicial approach: the schedule of pharmacy functioning and you would drug in the state of São Paulo

O presente trabalho tem como base a visão judicial da regulação sanitária no Estado de São Paulo no tocante à abertura e funcionamento de farmácias e drogarias em finais de semana e feriados fora dos horários previstos em lei. Essa é uma questão que enseja a atuação da Administração Pública por meio da Vigilância Sanitária e seus respectivos representantes legais e pode ocasionar autuações e fechamentos irregulares desses estabelecimentos. A função de regulação no âmbito da ação sanitária tem assumido, nos dias atuais, a agregação de sentido par a além da regulamentação ou controle do risco sanitário, ampliando significação no campo econômico.

Biochemical and hematological side effects of clofazimine in leprosy patients.

Gastrointestinal toxicity and red skin discoloration were the major side effects observed in leprosy patients undergoing long-term treatment with clofazimine (CFZ). Hematological and biochemical alterations have been cited among other side effects; however, their real magnitude and clinical significance at the doses currently employed in therapy have not been sufficiently documented. We therefore investigated the correlation between CFZ plasma concentration and biochemical (transaminases, bilirubins, alkaline phosphatase, gamma-glutamyltransferase, amylase, urea, creatinine, and potassium plasma levels) as well as hematological changes blood and reticulocyte counts, osmotic fragility, detection of Heinz bodies and methemoglobinemia (MHM), following in two regimes of treatment: CFZ as a single drug and CFZ as part of multidrug (MDT) therapy, in combination with dapsone and rifampicin. MHM and hemolytic anemia were detected in the MDT group only. Eosinophilia was found in patients of either group. Determination of hepatic, pancreatic and renal biochemical parameters showed rare, occasional changes of apparently no clinical significance. We conclude that CFZ is a generally well tolerated and safe drug when given as a daily dose of 50mg, which is currently used in leprosy patients.