Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

The heterogeneity of autoimmune polyendocrine syndrome type 1: Clinical features, new mutations and cytokine autoantibodies in a Brazilian cohort from tertiary care centers.

Autoimmune polyendocrine syndrome type 1 (APS1) is characterized by multiorgan autoimmunity. We aim at characterizing a multi-center Brazilian cohort of APS1 patients by clinical evaluation, searching mutation in the AIRE gene, measuring serum autoantibodies, and investigating correlations between findings. We recruited patients based on the clinical criteria and tested them for AIRE mutations, antibodies against interferon type I and interleukins 17A, 17F and 22. We identified 12 unrelated families (13 patients) with typical signs of APS1 in the proband, and the screening of relatives recognized an asymptomatic child. Candidiasis was present in all cases, and 19 other manifestations were observed. All patients carried one of 10 different mutations in AIRE, being 3 new ones, and were positive for anti-interferon type I serum antibody. Anti-interleukin-17A levels inversely correlated with the number of manifestations in each patient. This negative correlation may suggest a protective effect of anti-interleukin-17A with a potential therapeutic application.

Effects of low level laser therapy on attachment, proliferation, and gene expression of VEGF and VEGF receptor 2 of adipocyte-derived mesenchymal stem cells cultivated under nutritional deficiency.

Low-level laser therapy (LLLT) has been shown to increase the proliferation of several cell types. We evaluated the effects of LLLT on adhesion, proliferation, and gene expression of vascular endothelial growth factor (VEGF) and type 2 receptor of VEGF (VEGFR2) at mesenchymal stem cells (MSCs) from human (hMSCs) and rat (rMSCs) adipose tissues on nutritional deficiencies. A dose-response curve was performed with cells treated with laser Ga-Al-As (660 nm, 30 mW) at energy of 0.7 to 9 J. Cell adhesion and proliferation were quantified 20, 40, and 60 min after LLLT and 24, 72, and 120 h after cultivation. Gene expression was verified by RT-PCR after 2 h of LLLT. A minor nutritional support caused a significant decrease in proliferation and adhesion of hMSCs and rMSCs. However, at the lowest LLLT dose (0.7 J), we observed a higher proliferation in hMSCs at standard condition shortly after irradiation (24 h). Adhesion was higher in hMSCs cultivated in controlled conditions at higher LLLT doses (3 and 9 J), and rMSCs show a reduction in the adhesion on 1.5 to 9 J. On nutritional deprivation, a 9 J dose was shown to reduce proliferation with 24 h and adhesion to all culture times in rMSCs. VEGF and VEGFR2 were increased after LLLT in both cell types. However, hMSCs under nutritional deprivation showed higher expression of VEGF and its receptor after irradiation with other laser doses. In conclusion, LLLT on human and rat MSCs might upregulate VEGF messenger RNA (mRNA) expression and modulate cell adhesion and proliferation distinctively.

Factors Associated With Long Survival in Patients With Cancer Admitted to Palliative Care: An Exploratory Study.

Objective: Some patients with cancer admitted to palliative care have relatively long survivals of 1 year or more. The objective of this study was to find out factors associated with prolonged survival. Methods: Retrospective case-control study comparing the available data of patients with cancer who survived more than 1 year after admission in a palliative care service with patients with cancer who survived 6 months or less. The intended proportion was 4 controls for each case. Patients were identified through electronic records from 2012 until 2018. Results: And 1721 patients were identified. Of those patients, 111 (6.4%) survived for at least 1 year, and 363 (21.1%) were included as controls according to the established criteria. The intended proportion could not be reached; the proportion was only 3.3:1. The median survival of cases was 581 days (range: 371-2763), and the median survival of controls was 57 days (range: 1-182). In the multivariable analysis, patients with a hemoglobin ≥ 10.6 g/dL and a creatinine level >95 µmol/L had a higher probability of living more than 1 year. In contrast, patients with abnormal cognition, pain, anorexia, liver metastases, an Eastern Cooperative Oncology Group performance status >1, and a neutrophil/lymphocyte ratio ≥ 3.43 had a low probability of living more than 1 year. Conclusion: Several factors were statistically associated positively or negatively with prolonged survival. However, the data of this study should be confirmed in other studies.

Development of a Versatile Toolbox for Genetic Manipulation of Sporothrix brasiliensis.

Sporothrix brasiliensis has emerged as the most virulent species in the Sporothrix schenckii complex, accounting for sporotrichosis. Albeit the new insights into the understanding of host-pathogen interactions and comparative genomics of this fungi, the lack of genetic tools has hindered significant advances in this field of research. Here, we established an Agrobacterium tumefaciens-mediated transformation (ATMT) system to transform different strains of S. brasiliensis. We report parameters that account for a transformation efficiency of 3,179 ± 1,171 transformants/co-cultivation, which include the use of A. tumefaciens AGL-1 in a 2:1 ratio (bacteria:fungi) during 72 h at 26°C. Our data show that a single-copy transgene is transferred to S. brasiliensis that is mitotically stable in 99% of cells after 10 generations without selective pressure. In addition, we created a plasmid toolkit that allows the establishment of fusion proteins of any S. brasiliensis gene of interest with sGFP or mCherry under the control of the GAPDH or H2A endogenous promoters. These modules allow different levels of expression of the desired fusion. Moreover, we successfully targeted these fluorescent proteins to the nucleus and used fluorescence-tagged strains to assess phagocytosis. Overall, our data show that the ATMT system is an easy-to-use and efficient genetic toolbox for studies on recombinant expression and gene function in S. brasiliensis. IMPORTANCE Sporotrichosis is the most prevalent subcutaneous mycosis worldwide and has recently become a public health concern. Although immunocompetent hosts are also prone to sporotrichosis, immunodeficient hosts often develop a more severe and disseminated form of disease. To date, the Rio de Janeiro state in Brazil is the most significant feline zoonotic transmission epicenter in the world, with more than 4,000 human and feline diagnosed cases. Cats play an essential role in the S. brasiliensis infection due to their high susceptibility and transmissibility to other felines and humans. S. brasiliensis is the most virulent etiological agent of sporotrichosis, causing the most severe clinical manifestations. Despite the increasing incidence of sporotrichosis, the identification of virulence traits important for disease establishment, development, and severity has been lacking. In this work, we established an efficient genetic toolbox to manipulate S. brasiliensis that will guide future studies to define new virulence mechanisms and a better understanding of host-pathogen interactions from a molecular perspective.

The effects of three different low-volume aerobic training protocols on cardiometabolic parameters of type 2 diabetes patients: A randomized clinical trial.

Objective: To compare the effects of different aerobic training protocols on cardiometabolic variables in patients with type 2 diabetes mellitus (T2DM). Methods: This study was a parallel clinical trial. Fifty-two men and women with T2DM (>40 years) were randomly allocated into three groups, and 44 (22 males/22 females) were included in the final analysis. Exercise intensity was based on the speed corresponding to the maximum oxygen consumption (v V ˙ O2max). Moderate intensity continuous training (MICT) involved 14 minutes at 70% of v V ˙ O2max; short interval high-intensity interval training (S-HIIT) consisted of 20 bouts of 30 seconds at 100% of V˙O2max with 30 seconds passive recovery; long interval high-intensity training (L-HIIT) consisted of 5 bouts of 2 minutes at 100% of v V ˙ O2max with 2 minutes passive recovery. Training protocols were performed on a motorized treadmill two times per week for eight weeks. Glycated hemoglobin (Hb1Ac), total cholesterol, triglycerides, resting systolic blood pressure (SBP), resting diastolic blood pressure (DBP), resting heart rate (resting HR) and maximum oxygen consumption (V˙O2max) were measured before and after the exercise intervention. The study was registered on the Brazilian clinical trial records (ID: RBR45 4RJGC3). Results: There was a significant difference between groups for changes on V ˙ O2max. Greater increases on V ˙ O2max were achieved for L-HIIT (p = 0.04) and S-HIIT (p = 0.01) in comparison to MICT group, with no significant difference between L-HIIT and S-HIIT (p = 0.9). Regarding comparison within groups, there were significant reductions on HbA1c and triglycerides levels only for L-HIIT (p< 0.05). V ˙ O2max significantly increased for both L-HIIT (MD = 3.2 ± 1.7 ml/kg/min, p< 0.001) and S-HIIT (MD = 3.4 ± 1.7, p< 0.001). There was a significant reduction on resting SBP for L-HIIT group (MD = -12.07 ± 15.3 mmHg, p< 0.01), but not for S-HIIT and MICT. There were no significant changes from pre- to post-training on fasting glycemia, total cholesterol, HDL, LDL, resting HR and resting DBP for any group (p > 0.05). Conclusion: Low-volume HIIT promoted greater improvements in cardiorespiratory capacity in comparison with low-volume MICT, independent of the protocols used. There were no other differences between groups. All protocols improved at least one of the variables analyzed; however, the most evident benefits were after the high-intensity protocols, especially L-HIIT.

Glutamine Metabolism Supports the Functional Activity of Immune Cells against Aspergillus fumigatus.

The reprogramming of cellular metabolism of immune cells is an essential process in the regulation of antifungal immune responses. In particular, glucose metabolism has been shown to be required for protective immunity against infection with Aspergillus fumigatus. However, given the intricate cross talk between multiple metabolic networks and signals, it is likely that cellular metabolic pathways other than glycolysis are also relevant during fungal infection. In this study, we demonstrate that glutamine metabolism is required for the activation of macrophage effector functions against A. fumigatus. Glutamine metabolism was found to be upregulated early after fungal infection and glutamine depletion or the pharmacological inhibition of enzymes involved in its metabolism impaired phagocytosis and the production of both proinflammatory and T-cell-derived cytokines. In an in vivo model, inhibition of glutaminase increased susceptibility to experimental aspergillosis, as revealed by the increased fungal burden and inflammatory pathology, and the defective cytokine production in the lungs. Moreover, genetic variants in glutamine metabolism genes were found to regulate cytokine production in response to A. fumigatus stimulation. Taken together, our results demonstrate that glutamine metabolism represents an important component of the immunometabolic response of macrophages against A. fumigatus both in vitro and in vivo. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. The reprogramming of cellular metabolism is essential for innate immune cells to mount effective antifungal responses. In this study, we report the pivotal contribution of glutaminolysis to the host defense against A. fumigatus. Glutamine metabolism was essential both in vitro as well as in in vivo models of infection, and genetic variants in human glutamine metabolism genes regulated cytokine production in response to fungal stimulation. This work highlights the relevance of glutaminolysis to the pathogenesis of aspergillosis and supports a role for interindividual genetic variation influencing glutamine metabolism in susceptibility to infection.

Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.

Chronic pulmonary aspergillosis (CPA) is a devastating disease with increasing prevalence worldwide. The characteristic granulomatous-like inflammation poses as the major setback to effective antifungal therapies by limiting drug access to fungi. These inflammatory lung structures are reported to be severely hypoxic; nevertheless, the underlying mechanisms whereby these processes contribute to fungal persistence remain largely unknown. Hypoxia-inducible factor 1 alpha (HIF-1α), besides being the major cellular response regulator to hypoxia, is a known central immune modulator. Here, we used a model of Aspergillus fumigatus airway infection in myeloid-restricted HIF-1α knock-out (mHif1α-/- ) mice to replicate the complex structures resembling fungal granulomas and evaluate the contribution of HIF-1α to antifungal immunity and disease development. We found that fungal-elicited granulomas in mHif1α-/- mice had significantly smaller areas, along with extensive hyphal growth and increased lung fungal burden. This phenotype was associated with defective neutrophil recruitment and an increased neutrophil death, therefore highlighting a central role for HIF-1α-mediated regulation of neutrophil function in the pathogenesis of chronic fungal infection. These results hold the promise of an improved capacity to manage the progression of chronic fungal disease and open new avenues for additional therapeutic targets and niches of intervention.

Genetic Variation in PFKFB3 Impairs Antifungal Immunometabolic Responses and Predisposes to Invasive Pulmonary Aspergillosis.

Activation of immune cells in response to fungal infection involves the reprogramming of their cellular metabolism to support antimicrobial effector functions. Although metabolic pathways such as glycolysis are known to represent critical regulatory nodes in antifungal immunity, it remains undetermined whether these are differentially regulated at the interindividual level. In this study, we identify a key role for 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the immunometabolic responses to Aspergillus fumigatus. A genetic association study performed in 439 recipients of allogeneic hematopoietic stem cell transplantation (HSCT) and corresponding donors revealed that the donor, but not recipient, rs646564 variant in the PFKFB3 gene increased the risk of invasive pulmonary aspergillosis (IPA) after transplantation. The risk genotype impaired the expression of PFKFB3 by human macrophages in response to fungal infection, which was correlated with a defective activation of glycolysis and the ensuing antifungal effector functions. In patients with IPA, the risk genotype was associated with lower concentrations of cytokines in the bronchoalveolar lavage fluid samples. Collectively, these findings demonstrate the important contribution of genetic variation in PFKFB3 to the risk of IPA in patients undergoing HSCT and support its inclusion in prognostic tools to predict the risk of fungal infection in this clinical setting. IMPORTANCE The fungal pathogen Aspergillus fumigatus can cause severe and life-threatening forms of infection in immunocompromised patients. Activation of glycolysis is essential for innate immune cells to mount effective antifungal responses. In this study, we report the contribution of genetic variation in the key glycolytic activator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) to the risk of invasive pulmonary aspergillosis (IPA) after allogeneic hematopoietic stem cell transplantation. The PFKFB3 genotype associated with increased risk of infection was correlated with an impairment of the antifungal effector functions of macrophages in vitro and in patients with IPA. This work highlights the clinical relevance of genetic variation in PFKFB3 to the risk of IPA and supports its integration in risk stratification and preemptive measures for patients at high risk of IPA.

Epigastric Pain and Weight Loss - A Case of Wilkie's Syndrome.

Superior mesenteric artery syndrome (SMA syndrome) or Wilkie's syndrome is a rare etiology of duodenal obstruction due to compression of the third portion of the duodenum between the superior mesenteric artery and the aorta. Physical and laboratory findings are often non-specific but imaging methods are useful for diagnosing the condition. A 46-year-old female patient presented to the outpatient clinic of our internal medicine department with a 2-year history of epigastric pain, nausea, early satiety and weight loss of 15 kg. Previous studies were inconclusive. The patient underwent computed tomography enterography and its findings were consistent with SMA syndrome. Currently the patient is being followed by General Surgery and Nutrition and is under nutritional measures in order to optimize her body mass index to decrease possible surgical complications. This case report emphasizes the importance of clinical suspicion and careful investigation when considering less common etiologies for frequent gastrointestinal symptoms. LEARNING POINTS: Superior mesenteric artery syndrome is a rare cause of upper gastrointestinal system obstruction and its diagnosis is often delayed.This syndrome should be suspected in the differential diagnosis of patients with persistent nausea, abdominal pain and significant weight loss.

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.

Evaluation of the hypothalamic-pituitary-adrenal axis in a case series of familial partial lipodystrophy.

BACKGROUND: Familial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis, but little is known about its activity in FPL. METHODS: Patients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone). RESULTS: Six patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed. CONCLUSIONS: Our findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.

Propylthiouracil-induced agranulocytosis as a rare complication of antithyroid drugs in a patient with Graves' disease.

INTRODUCTION: Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism. Antithyroid drugs (ATDs) are available as therapy. Agranulocytosis is a rare but potentially fatal complication of this therapy. In this study, we report agranulocytosis induced by propylthiouracil (PTU) in a patient with GD and the difficulties of clinical management. CASE: RNBA, male, 30 years old, with GD, treated with propylthiouracil (PTU). He progressed with pharyngotonsillitis. Then, PTU was suspended and antibiotic, filgrastim, propranolol, and prednisone were initiated. Due to the decompensation of hyperthyroidism, lithium carbonate, dexamethasone, and Lugol's solution were introduced. Total thyroidectomy (TT) was performed with satisfactory postoperative progression. DISCUSSION: We describe here the case of a young male patient with GD. For the treatment of hyperthyroidism, thioamides are effective options. Agranulocytosis induced by ATDs is a rare complication defined as the occurrence of a granulocyte count <500/mm3 after the use of ATDs. PTU was suspended, and filgrastim and antibiotics were prescribed. Radioiodine (RAI) or surgery are therapeutic alternatives. Due to problems with ATD use, a total thyroidectomy was proposed. The preoperative preparation was performed with beta-blocker, glucocorticoid, lithium carbonate, and Lugol solution. Cholestyramine is also an option for controlling hyperthyroidism. TT was performed without postoperative complications. CONCLUSION: Thionamide-induced agranulocytosis is a rare complication. With a contraindication to ATDs, RAI and surgery are definitive therapeutic options in GD. Beta-blockers, glucocorticoids, lithium carbonate, iodine, and cholestyramine may be an adjunctive therapy for hyperthyroidism.

Adipose tissue expression of 11beta-hydroxysteroid dehydrogenase type 1 in Cushing's syndrome and in obesity.

Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a NADPH-dependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11betaHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11betaHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11betaHSD1 also in human adipose tissue. However, 11betaHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11betaHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11betaHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11betaHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.

[Möbius sequence: long-term strabismus surgical outcome]. / Seqüência de Möbius: resultados a longo prazo, da correção cirúrgica do estrabismo.

PURPOSE: To analyze the long-term results in a consecutive series of Möbius sequence patients, who underwent surgical correction of strabismus. METHODS: Ten patients with Möbius sequence fulfilled the inclusion criteria of this study. All patients presented esotropia at the preoperative examination, above or equal to 15 prismatic diopters (DP) varying from 15 to 85. All patients presented lateral rectus muscles severe underaction, six presented hipertropia above or equal 10 DP associated with esodeviation, and five presented anisotropia in A or in V. The patients were operated upon protocol, in a consecutive way, in July 2002. Patients were reexamined periodically, and at 2nd postoperative year as for: the visual acuity; deviation measurements; ocular rotations; cosmetic aspect and socialization. RESULTS: The patients presented satisfactory surgical results in eight cases, considering an eso or exodeviation up to 15 DP and a hipertropia lower than 10 DP. Four (40%) patients presented correction of the preoperative anisotropia. Variation of ocular deviation in the primary position (from the 90th day to the 2nd postoperative year was observed) in 9 patients (90%), demonstrating that strabismus surgical stabilization needs time. CONCLUSIONS: The surgical results were considered satisfactory, improving patient self-esteem and the parent satisfaction, making the social inclusion easier.

[Study of retinal nerve fiber layer in patients with schistosomiasis mansoni: analysis with GDX]. / Estudo da camada de fibras nervosas da retina em pacientes com esquistossomose mansônica: análise com GDx.

PURPOSE: To study the retinal nerve fiber layer in young patients suffering from hepatosplenic schistosomiasis mansoni. METHODS: Twenty-three patients with hepatosplenic schistosomiasis mansoni who were submitted, when children, to splenectomy, ligature of the left gastric vein and auto-implantation of spleen tissue in the major omentum underwent GDx Scanning Laser System evaluations. All patients presented with intraocular pressure below 21 mmHg. RESULTS: Only one patient suffering from hepatosplenic schistosomiasis mansoni showed abnormalities on the GDx examination. There were no abnormalities on GDx examination in the control group. CONCLUSION: There was no significant difference between the two groups of this study. Only one patient showed retinal nerve fiber layer reduction.

[Retinal nerve fiber layer alteration in chronic users of chloroquine]. / Alteração da camada de fibras nervosas da retina em usuários crônicos de cloroquina.

PURPOSES: To evaluate the retina nerve fiber layer by laser polarimetry in patients in chronic use of chloroquine. METHODS: Forty-four eyes of twenty-two patients were studied. These were in use of chloroquine due to rheumatic diseases during at least one year. As a control group, twenty patients without use of chloroquine with similar characteristics (age, gender and race) were included. Patients who had a family history of ocular hypertension or glaucoma were not included in this group. Both eyes were submitted to analysis of the retina nerve fiber layer with a GDx Nerve Fiber Analyzer. RESULTS: In 28 eyes (63.6%) of chronic chloroquine users, alterations in more than two parameters by GDx were found. There was alteration in the Deviation from the normal graph with a loss of nerve fibers in 11 eyes (25%). When these results were compared with the control group, there was a significant statistical difference between the following parameters: Superior Ratio, Inferior Ratio, Superior Nasal, Elipse Modulation, The Number, Superior Average and Superior Integral. There was also a significant statistical association between the time of chloroquine use and loss of nerve fiber layer. CONCLUSIONS: From the results the following conclusion can be drawn: the chronic use of chloroquine was associated with alteration of the nerve fiber layer. Thus these results may contribute to early diagnosis of nerve fiber layer loss in chloroquine retinopathy.

Neonatal treatment with fluoxetine reduces depressive behavior induced by forced swim in adult rats.

Serotonin plays a role at the pathophysiology of depression in humans and in experimental models. The present study investigated the depressive behavior and the weigh evolution in adult rats (60 days) treated from the 1st to the 21st postnatal day with fluoxetine, a selective serotonin reuptake inhibitor (10 mg/kg, sc, daily). The depressive behavior was induced by the forced swim test (FST). The animals were submitted to two sessions of FST: 1st session for 15 min and the 2nd session 24h later, for 5 min. During the 2nd session the Latency of the Attempt of Escape (LAE) and Behavioral Immobility (BI) were appraised. The Fluoxetine group when compared to the Control group, showed an increase in LAE and a decrease in BI. The neonatal administration of fluoxetine reduced the depressive behavior in adult rats, possibly by increase in the brain serotonergic activity. This alteration can be associated to process of neuroadaptation.