Root trunk height as a risk factor for periodontal furcation involvement in maxillary first molars: an in vitro study.

The aim of this study was to correlate the root trunk height from the furcation openings on the buccal, mesial and distal surfaces to the cemento-enamel junction in upper first permanent molars in human beings with risk for periodontal disease progression. One hundred extracted maxillary first molars were used. Reference points and demarcations were determined from the entrance of the buccal (F1), mesial (F2) and distal (F3) furcations to the cemento-enamel junction in millimeters. The mean distances found were 3.50 mm, 4.44 mm and 4.26 mm for the buccal, mesial and distal furcations, respectively, in relation to the cemento-enamel junction. The statistical analyses were Student's t-test and Chi-square (X2). With periodontal disease progression, the buccal furcation presents a greater compromising risk due to its proximity to the cemento-enamel junction, while the mesial furcation is the most distant, comprising a lesser risk.

Diabetes and pregnancy: An update of the problem

Pregnancies complicated by diabetes account for about 7% of all pregnancies attended by the Brazilian Unified Healthcare System (SUS) and are one of the main causes of maternal/perinatal morbidity and mortality in Brazil. Considering the importance of this topic, this article presents an update of diabetes classification, diagnostic criteria, maternal/perinatal outcomes, and both clinical and obstetric prenatal care. Even though there is no consensus about screening and diagnostic standards, the investigation of hyperglycemia in all risk pregnancies is recommended. The importance of adequate metabolic control is emphasized in order to improve maternal and neonatal outcomes. Finally, the development of educational programs is encouraged, viewing not only good gestational outcome but also long-term changes in the lifestyle of these women. © by São Paulo State University.

Paracoccidioidomicose é esporotricose associada à imunossupressão

Paracoccidioidomycosis is caused by Paracoccidioides brasiliensis, a dimorphic fungus, prevalent in tropical and subtropical America. It is rare in the United States of America, Canada, Asia and Europe and in these countries it is related to immigrants from endemic areas. Paracoccidioidomycosis associated with immunosuppression runs a course with rapid progression and dissemination of the disease, with many cutaneous lesions. The mortality rate is up to 35% when associated with HIV infection or AIDS. The diagnosis depends on visualization of the agent through direct examination, histopathology, or culture. First choice treatment is done with Amphotericin B deoxycholate. Itraconazole is an option for long term treatment. Sporotrichosis is caused by Sporothrix schenckii, the species of reference. Other species have been considered such as: Sporothrix brasiliensis, S.globosa and S.mexicana and the S.schenckii var. lurei. It is a ubiquitous disease although more prevalent in tropical and subtropical areas. Currently, it has been reported as a zoonotic disease of cats and dogs, with transmission to their owners in the city of Rio de Janeiro (Brazil). Sporotrichosis associated to immunosuppression is uncommon or underreported. There were 34 cases in association with HIV infection or AIDS reported so far. Presenting with disseminated disease and non cutaneous lesions including joints, lungs and central nervous system. Amphotericin B deoxycholate is the first choice for treatment and itraconazol considered an alternative.

Role of stressful and traumatic life events in obsessive-compulsive disorder

Whilst genetic factors are thought to contribute to the development of obsessive-compulsive disorder (OCD), the role of environmental factors in OCD is only beginning to be understood. In this article, we review the influence of stress-related factors in OCD. Overall, studies indicate that: patients with OCD frequently report stressful and traumatic life events before illness onset, although these rates do not seem to be significantly different from those described in other disorders; the association between OCD and post-traumatic stress disorder (PTSD) might result from symptom overlap, although cases of patients developing OCD after PTSD and showing obsessive-compulsive symptoms that were unrelated to trauma have been described fairly consistently; it is unclear whether patients with OCD and a history of stress-related factors (including stressful life events, traumatic life events or comorbid PTSD) may respond better or worse to the available treatments; and comorbid PTSD may modify the clinical expression of OCD-although controlled studies comparing pre-versus post-traumatic OCD patients are still unavailable. In conclusion, there is a growing evidence to suggest a role for stress-related factors in OCD. Although the available literature does not confirm the existence of a post-traumatic subtype of OCD, it does call for further systematic research into this topic. © 2011 Future Medicine Ltd.

Modelo experimental de úlcera traumática em mucosa jugal de ratos

Purpose: To establish an experimental model of traumatic ulcer in rat cheek mucosa for utilization in future alternative therapy studies. Methods: A total of 60 adult male rats (250 - 300g) were used. Ulceration of the left cheek mucosa was provoked by abrasion using a n o 15 scalpel blade. The animals were observed for 10 days, during which they were weighed and their ulcers were measured. The histological characteristics were analyzed and scored according to the ulcer phase. In the statistical analysis, a value of p<0.01 was considered a statistically significant response in all cases. Results: During the five first days, the animals lost weight (Student t test, p<0.01). The ulcerated area receded linearly over time and was almost completely cicatrized after 10 days (ANOVA, Tendency post-test, p<0.0001). Groups on days 1, 2 and 3 days displayed similar results, but a decrease in scores were observed after the 4th day. Conclusion: The proposed cheek mucosa ulcer model in rats can be considered an efficient, low-cost, reliable, and reproducible method.

Mast cells modulate the inflammatory process in endotoxin-induced uveitis

Purpose: To investigate the role of mast cells and annexin-A1 (Anxa1) in endotoxin-induced uveitis (EIU). Methods: EIU was induced by injection of lipopolysaccharide (LPS) into the paws of rats, which were then sacrificed after 24 and 48 h. To assess EIU in the absence of mast cells, groups of animals were pretreated with compound 48/80 (c48/80) and sacrificed after 24 h after no treatment or EIU induction. The eyes were used for histological studies and the aqueous humor (AqH) pool was used for the analysis of transmigrated cells and Anxa1 levels. In inflammatory cells, Anxa1 expression was monitored by immunohistochemistry. Results: After 24 h, rats with EIU exhibited degranulated mast cells, associated with elevated numbers of infiltrating leukocytes and the high expression of Anxa1 in the AqH and the neutrophils. After 48 h of EIU, the mast cells were intact, indicating granule re-synthesis, and there was a reduction of neutrophil transmigration and an increase in the number of mononuclear phagocytic cells in ocular tissues. Anxa1 expression was decreased in neutrophils but increased in mononuclear phagocytic cells. In the animals pretreated with c48/80 and subjected to EIU, mast cells responded to this secretagogue by degranulating and few transmigrated neutrophils were observed. Conclustions: We report that mast cells are a potential source of pharmacological mediators that are strongly linked to the pathophysiology of EIU, and the endogenous protein Anxa1 is a mediator in the homeostasis of the inflammatory process with anti-migratory effects on leukocytes, which supports further studies of this protein as an innovative therapy for uveitis. © 2011 Molecular Vision.

Topical use of fluorides for caries control

Since the early findings on the protective effects of fluoride present in drinking water upon caries incidence and prevalence, intensive research has been conducted in order to determine the benefits, safety, as well as the cost-effectiveness of other modalities of fluoride delivery. The present chapter reviews the various forms of topical fluoride use - professionally and self-applied - with special emphasis on clinical efficacy and possible side effects. The most widely used forms of fluoride delivery have been subject of several systematic reviews, providing strong evidence supporting the use of dentifrices, gels, varnishes and mouth rinses for the control of caries progression. Dentifrices with fluoride concentrations of 1,000 ppm and above have been shown to be clinically effective in caries prevention when compared to a placebo treatment, but the evidence regarding formulations with 450-550 ppm is still subject of debate. Therefore, the recommendation for low-fluoride dentifrice use must take into account both risks and benefits. The evidence for the combined use of two modalities of fluoride application in comparison to a single modality is still inconsistent, implying that more studies with adequate methodology are needed to determine the real benefits of each method. Considering the currently available evidence and risk-benefit aspects, it seems justifiable to recommend the use of fluoridated dentifrices to individuals of all ages, and additional fluoride therapy should also be targeted towards individuals at high caries risk. © 2011 S. Karger AG, Basel.

Involvement of the atrial natriuretic peptide in cardiovascular pathophysiology and its relationship with exercise

In this minireview we describe the involvement of the atrial natriuretic peptide (ANP) in cardiovascular pathophysiology and exercise. The ANP has a broad homeostatic role and exerts complex effects on the cardio-circulatory hemodynamics, it is produced by the left atrium and has a key role in regulating sodium and water balance in mammals and humans. The dominant stimulus for its release is atrial wall tension, commonly caused by exercise. The ANP is involved in the process of lipolysis through a cGMP signaling pathway and, as a consequence, reducing blood pressure by decreasing the sensitivity of vascular smooth muscle to the action of vasoconstrictors and regulate fluid balance. The increase of this hormone is associated with better survival in patients with chronic heart failure (CHF). This minireview provides new evidence based on recent studies related to the beneficial effects of exercise in patients with cardiovascular disease, focusing on the ANP. © 2012 de Almeida et al; licensee BioMed Central Ltd.

Virus-host interaction in feline immunodeficiency virus (FIV) infection

Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. © 2013 Elsevier Ltd. All rights reserved.

Clinical features of pure obsessive-compulsive disorder

Objective Psychiatric comorbidity is the rule in obsessive-compulsive disorder (OCD); however, very few studies have evaluated the clinical characteristics of patients with no co-occurring disorders (non-comorbid or pure OCD). The aim of this study was to estimate the prevalence of pure cases in a large multicenter sample of OCD patients and compare the sociodemographic and clinical characteristics of individuals with and without any lifetime axis I comorbidity. Method A cross-sectional study with 955 adult patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders (C-TOC). Assessment instruments included the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, The USP-Sensory Phenomena Scale and the Brown Assessment of Beliefs Scale. Comorbidities were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders. Bivariate analyses were followed by logistic regression. Results Only 74 patients (7.7%) presented pure OCD. Compared with those presenting at least one lifetime comorbidity (881, 92.3%), non-comorbid patients were more likely to be female and to be working, reported less traumatic experiences and presented lower scores in the Y-BOCS obsession subscale and in total DY-BOCS scores. All symptom dimensions except contamination-cleaning and hoarding were less severe in non-comorbid patients. They also presented less severe depression and anxiety, lower suicidality and less previous treatments. In the logistic regression, the following variables predicted pure OCD: sex, severity of depressive and anxious symptoms, previous suicidal thoughts and psychotherapy. Conclusions Pure OCD patients were the minority in this large sample and were characterized by female sex, less severe depressive and anxious symptoms, less suicidal thoughts and less use of psychotherapy as a treatment modality. The implications of these findings for clinical practice are discussed. © 2013 Elsevier Inc. All rights reserved.

Avaliação clinimétrica do desfecho em uma série de casos de Lúpus Eritomatoso Sistêmico Juvenil (LESJ)

Pós-graduação em Saúde Coletiva - FMB

Exaggerating, mislabeling or simulating obsessive-compulsive symptoms: Case reports of patients claiming to have obsessive-compulsive disorder

Background: There are no reported cases of factitious or simulated obsessive compulsive disorder (OCD). However, over the last years, our clinic has come across a number of individuals that seem to exaggerate, mislabel or even intentionally produce obsessive and/or compulsive symptoms in order to be diagnosed with OCD.Methods: In this study, experienced clinicians working on a university-based OCD clinic were requested to provide clinical vignettes of patients who, despite having a formal diagnosis of OCD, were felt to display non-genuine forms of this condition.Results: Ten non-consecutive patients with a self-proclaimed diagnosis of OCD were identified and described. Although patients were diagnosed with OCD according to various structured interviews, they exhibited diverse combinations of the following features: (i) overly technical and/or doctrinaire description of their symptoms, (ii) mounting irritability, as the interviewer attempts to unveil the underlying nature of these descriptions; (iii) marked shifts in symptom patterns and disease course; (iv) an affirmative yes pattern of response to interview questions; (v) multiple Axis I psychiatric disorders; (vi) cluster B features; (vii) an erratic pattern of treatment response; and (viii) excessive or contradictory drug-related side effects.Conclusions: In sum, reliance on overly structured assessments conducted by insufficiently trained or naive personnel may result in invalid OCD diagnoses, particularly those that leave no room for clinical judgment. (C) 2014 Elsevier Inc. All rights reserved.

Proposta de um protocolo de terapia celular para o tratamento da doença pulmonar obstrutiva crônica

The main feature of pulmonary emphysema is airflow obstruction resulting from the destruction of the alveolar walls distal to the terminal bronchioles. Existing clinical approaches have improved and extended the quality of life of emphysema patients. However, no treatment currently exists that can change the disease course and cure the patient. The different therapeutic approaches that are available aim to increase survival and/or enhance the quality of life of emphysema patients. In this context, cell therapy is a promising therapeutic approach with great potential for degenerative pulmonary diseases. In this protocol proposition, all patients will be submitted to laboratory tests, such as evaluation of heart and lung function and routine examinations. Stem cells will be harvested by means of 10 punctures on each anterior iliac crest, collecting a total volume of 200 mL bone marrow. After preparation, separation, counting and labeling (optional) of the mononuclear cells, the patients will receive an intravenous infusion from the pool of Bone Marrow Mononuclear Cells (BMMC). This article proposes a rational and safe clinical cellular therapy protocol which has the potential for developing new projects and can serve as a methodological reference for formulating clinical application protocols related to the use of cellular therapy in COPD. This study protocol was submitted and approved by the Brazilian National Committee of Ethics in Research (CONEP - Brazil) registration number 14764. It is also registered in ClinicalTrials.gov (NCT01110252). (c) 2013 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved.

Der Einfluss einer wildtypischen SOD1-Untereinheit auf Konformation und Stabilität mutanter SOD1-Heterodimere

Die Erkrankung Amyotrophe Lateralsklerose (ALS) ist gekennzeichnet durch eine progressive Degeneration der Motoneurone. Die hierdurch im Patienten hervorgerufene fortschreitende Paralyse kann von wenigen Wochen über Monate bis zu mehreren Jahren variieren. Im Durchschnitt beträgt die Krankheitsdauer 3 - 5 Jahre. Häufig führt respiratorische Insuffizienz letztendlich zum Tod des Patienten. ALS ist bis heute unheilbar. Etwa 10 % aller ALS Fälle zeigen einen familiären Hintergrund. Hiervon werden ~20 % durch Mutationen im Gen des antioxidativen Enzyms CuZnSuperoxiddismutase (SOD1) verursacht. Mehr als 150 Mutationen im Gen der SOD1 wurden bisher als Auslöser der ALS beschrieben. Durch die Mutation erlangen SOD1 Proteine zusätzliche, bisher jedoch unbekannte toxische Eigenschaften. Ein dismutaseaktives SOD1 Enzym setzt sich aus zwei SOD1 Untereinheiten zusammen. Aufgrund der autosomal dominanten Vererbung der Krankheit kann ein SOD1 Dimer im Patienten als wildtypisches Homodimer (SOD1WT‑WT), als mutantes Homodimer (SOD1mut‑mut) oder als Heterodimer (SOD1mut-WT) vorliegen. In dieser Arbeit wurden SOD1 Dimere untersucht, deren Untereinheiten kovalent miteinander verbunden waren. Es konnte gezeigt werden, dass sich die biochemischen und biophysikalischen Eigenschaften mutanter SOD1 Heterodimere von mutanten SOD1 Homodimeren mit der gleichen Mutation unterschieden. Mutante SOD1 Heterodimere wiesen eine höhere Resistenz gegen einen Abbau durch Proteinase K auf als ihre korrespondierenden Homodimere. Des Weiteren verminderte eine wildtypische Untereinheit die Interaktion der Heterodimere mit Antikörpern gegen fehlgefaltete SOD1. Die Sekundärstruktur der mutanten SOD1 Heterodimere unterschied sich hierbei nicht auffällig von der Sekundärstruktur ihrer zugehörigen Homodimere. Eine wildtypische Untereinheit verändert somit möglicherweise die Tertiärstruktur seiner kovalent gebundenen mutanten SOD1 Untereinheit und/oder die Konformation des gesamten Dimerproteins. Durch die Mutation bedingte Missfaltungen werden hierdurch reduziert, die Stabilität des Dimers gegenüber proteolytischem Abbau erhöht. Nach der Aufreinigung der Dimerproteine wies das mutanten SOD1 Heterodimer diese Eigenschaften nicht mehr auf. Ein potentieller Interaktionspartner, der eine verminderte Fehlfaltung des Heterodimers oder eine verstärkte Missfaltung des Homodimers fördert, könnte hierbei während der Aufreinigungsprozedur verlorengegangen sein. Die hier nachgewiesene Konformationsänderung könnte über einen Prionen-ähnlichen Effekt übertragen werden und die erhöhte Stabilität das mutante, toxische Protein vor Degradation schützen. Dies korreliert mit der Beobachtung früherer Studien, in denen nachgewiesen wurde, dass mutante SOD1 Heterodimere potentiell toxischer sind als ihre korrespondierenden Homodimere.

Blood-CNS barriers in neurodegenerative diseases

The blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) separate the brain and the spinal cord from the circulating blood and are important for the maintenance of the CNS homeostasis. They build a physical barrier thereby protecting the CNS from pathogens and toxic agents, and their disruption plays a crucial role in the pathogenesis of several CNS disorders. In this thesis, the blood-CNS-barriers were studied via in vitro models in two case studies for neurodegenerative disorders, in particular Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). The first model evaluates treatment possibilities of AD using nanotechnology-based strategies. Since the toxic amyloid-β42 (Aβ42) peptide plays a crucial role in the pathogenesis of AD, reduced generation or enhanced clearance of Aβ42 peptides are expected to modify the disease course in AD. Therefore, several Aβ42-lowering drugs like flurbiprofen had been tested in clinical trials, but most of them failed due to their low brain penetration. Here, flurbiprofen was embedded in polylactide (PLA) nanoparticles and its transport was examined in an in vitro BBB model. The embedding of flurbiprofen into the nanoparticles disguised its cytotoxic potential and enabled the administration of higher drug concentrations which resulted in a sufficient transport of the drug across an endothelial cell monolayer. These results demonstrate that non-permeable drugs can be transported efficiently via nanoparticles and that these nanotechnology-based strategies are a promising tool to generate novel therapeutic options for AD and other CNS diseases. rnThe focus of the second project was to investigate the impaired integrity of the BSCB in a mouse model for ALS. About 20% of all familial ALS cases are associated with missense mutations or small deletions in the gene that encodes Cu/Zn-superoxide dismutase 1 (SOD1). To date, the molecular mechanisms resulting in ALS are still unknown, but there is evidence that the disruption of the BSCB is one of the primary pathological events. In both familial and sporadic ALS patients, loss of endothelial integrity and endothelial cell damage was observed, and studies with SOD1 transgenic mice demonstrated that the BSCB disruption was found prior to motor neuron degeneration and neurovascular inflammation. Thus, an in vitro model for ALS endothelial cells was generated which exhibited comparable integrity characteristics and tight junction (TJ) protein expression profiles as isolated primary endothelial cells of the BSCB of SOD1 transgenic mice. In this, an alteration of the βcat/AKT/FoxO1 pathway, which regulates the expression of the TJ protein claudin-5, could be observed. These data furthermore indicate that ALS is a neurovascular disease, and understanding of the primary events in ALS pathogenesis will hopefully provide ideas for the development of new therapeutic strategies. rn