Pituitary metastases: presentation and outcomes from a pituitary center over the last decade.

PURPOSE: Highlight and characterize manifestations, diagnostic/management approaches and outcomes in a contemporary cohort of patients with pituitary metastases (PM) from a large European pituitary center-over 10 years. METHODS: Retrospective review of PM cases between 1/2009 and 12/2018. Clinical, laboratory, imaging data at PM detection and during follow-up were analysed. RESULTS: 18 cases were identified (14 females; median age at diagnosis 61.5 years). Most common primary malignancies were lung (39%) and breast (32%). Most frequent presenting manifestation was visual dysfunction (50%). Gonadotrophin, ACTH, TSH deficiency were diagnosed in 85%, 67%, 46% of cases, respectively; diabetes insipidus (DI) was present in 17%. 33% of cases were detected during investigation for symptoms unrelated to PM. PM management included radiotherapy (44%), transsphenoidal surgery (17%), transsphenoidal surgery and radiotherapy (6%) or monitoring only (33%). One-year survival was 49% with median survival from PM detection 11 months (range 2-47). CONCLUSIONS: In our contemporary series, clinical presentation of PM has evolved; we found increased prevalence of anterior hypopituitarism, decreased rates of DI and longer survival compared with older literature. Increased availability of diagnostic imaging, improvements in screening and recognition of pituitary disease and longer survival of patients with metastatic cancer may be contributing factors.

Endosomal dysfunction impacts extracellular vesicle release: Central role in Aß pathology.

Alzheimer's Disease (AD) is characterized by progressive loss of cognitive abilities; senile plaques represent the major histopathological findings. Amyloid precursor protein (APP) processing machinery, and its product amyloid-beta (Aß) peptide, have been found in extracellular vesicles (EVs), specifically exosomes, which allows for Aß peptide aggregation and subsequent senile plaques deposition. We review the APP processing imbalance in EVs, autophagic and endosomal pathways in AD. Increased intraluminal vesicle (ILV) production and exosome release appear to counteract the endosomal dysfunction of APP processing; however, this process results in elevated amyloidogenic processing of APP and augmented senile plaque deposition. Several players related to APP processing and dysfunctional endosomal-lysosomal-exosomal (and other EVs) pathway are described, and the interconnected systems are discussed. The components Arc, p75, Rab11 and retromer complex emerge as candidates for key convergent mechanisms that lead to increased EVs loaded with APP machinery and Aß levels, in atrophy and damage of basal forebrain cholinergic neurons in AD.

Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Activity and in vivo tracking of Amphotericin B loaded PLGA nanoparticles.

The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.

Does low-level laser therapy decrease swelling and pain resulting from orthognathic surgery?

Low-level laser therapy (LLLT) could be an alternative for the treatment of swelling and pain after orthognathic surgery, but there is a paucity of data in the literature on the effects of its use. This study verified the efficacy of an LLLT protocol to reduce swelling and pain after orthognathic surgery. Ten healthy patients who underwent a bilateral sagittal split with Le Fort I osteotomy were randomly selected for this study. The LLLT protocol consisted of intraoral and extraoral application to one side of the face after surgery (irradiated side); application to the other side was simulated (non-irradiated side). The irradiated and non-irradiated sides were compared regarding the swelling coefficient and were assessed for pain using a visual analogue scale. There were no significant differences between the irradiated and non-irradiated sides regarding swelling and pain in the immediate postoperative assessment. Swelling decreased significantly on the irradiated side in the postoperative assessments on days 3, 7, 15, and 30. Self-reported pain was less intense on the irradiated side at the 24-h (1.2 vs. 3.4) and 3-day (0.6 vs. 2.1) assessments, but at 7 days after surgery neither side showed pain. This LLLT protocol can improve the tissue response and reduce the pain and swelling resulting from orthognathic surgery.

Neonatal morphine administration leads to changes in hippocampal BDNF levels and antioxidant enzyme activity in the adult life of rats.

It is know that repeated exposure to opiates impairs spatial learning and memory and that the hippocampus has important neuromodulatory effects after drug exposure and withdrawal symptoms. Thus, the aim of this investigation was to assess hippocampal levels of BDNF, oxidative stress markers associated with cell viability, and TNF-α in the short, medium and long term after repeated morphine treatment in early life. Newborn male Wistar rats received subcutaneous injections of morphine (morphine group) or saline (control group), 5 µg in the mid-scapular area, starting on postnatal day 8 (P8), once daily for 7 days, and neurochemical parameters were assessed in the hippocampus on postnatal days 16 (P16), 30 (P30), and 60 (P60). For the first time, we observed that morphine treatment in early life modulates BDNF levels in the medium and long term and also modulates superoxide dismutase activity in the long term. In addition, it was observed effect of treatment and age in TNF-α levels, and no effects in lactate dehydrogenase levels, or cell viability. These findings show that repeated morphine treatment in the neonatal period can lead to long-lasting neurochemical changes in the hippocampus of male rats, and indicate the importance of cellular and intracellular adaptations in the hippocampus after early-life opioid exposure to tolerance, withdrawal and addiction.

Effect of different exercise protocols on histone acetyltransferases and histone deacetylases activities in rat hippocampus.

Regular and moderate exercise has been considered an interesting neuroprotective strategy. Although the mechanisms by which physical exercise alters brain function are not clear, it appears that neuroprotective properties of exercise could be related to chromatin remodeling, specifically the induction of histone acetylation through modulation of histone deacetylases (HDAC) and histone acetyltransferases (HAT) activities. The aim of the present work was to investigate the effect of exercise on HDAC and HAT activities in rat whole hippocampus at different times after treadmill. Adult male Wistar rats were assigned to non-exercised (sedentary) and exercised groups on different protocols: a single session of treadmill exercise (running for 20 min) and a chronic treadmill protocol (running once daily for 20 min, for 2 weeks). The effects of exercise on HDAC and HAT activities were measured immediately, 1 h and 18 h after the single session or the last training session of chronic treadmill exercise using specific assay kits. The single session of treadmill exercise reduced HDAC activity, increased HAT activity and increased the HAT/HDAC balance in rat hippocampus immediately and 1 h after exercise, an indicative of histone hyperacetylation status. The acetylation balance was also influenced by the circadian rhythm, since the HAT/HDAC ratio was significantly decreased in the early morning in all groups when compared to the afternoon. These data support the hypothesis that exercise neuroprotective effects may be related, at least in part, to acetylation levels through modulation of HAT and HDAC activities. We also demonstrated circadian changes in the HAT and HDAC activities and, consequently, in the acetylation levels.

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02).

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate.

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02).

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

High HTLV-1 proviral load, a marker for HTLV-1 associated myelopathy/tropical spastic paraparesis, is also detected in patients with infective dermatitis associated with HTLV-1.

Salvador (BA, Brazil) is an endemic area for human T-cell lymphotrophic virus type 1 (HTLV-1). The overall prevalence of HTLV-1 infection in the general population has been estimated to be 1.76%. HTLV-1 carriers may develop a variety of diseases such as adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and infective dermatitis associated with HTLV-1 (IDH). IDH is a chronic and severe form of childhood exudative and infective dermatitis involving mainly the scalp, neck and ears. It has recently been observed that 30% of patients with IDH develop juvenile HAM/TSP. The replication of HTLV-1 has been reported to be greater in adult HAM/TSP patients than in asymptomatic HTLV-1 carriers. In the current study, the proviral load of 28 children and adolescents with IDH not associated with HAM/TSP was determined and the results were compared to those obtained in 28 HTLV-1 adult carriers and 28 adult patients with HAM/TSP. The proviral load in IDH patients was similar to that of patients with HAM/TSP and much higher than that found in HTLV-1 carriers. The high levels of proviral load in IDH patients were not associated with age, duration of illness, duration of breast-feeding, or activity status of the skin disease. Since proviral load is associated with neurological disability, these data support the view that IDH patients are at high risk of developing HAM/TSP.

Infective dermatitis has similar immunological features to human T lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis.

Human T lymphotropic virus-type 1 (HTLV-1) is the causal agent of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T cell leukaemia/lymphoma and infective dermatitis associated with HTLV-1 (IDH). Over-production of proinflammatory cytokines and an increase in HTLV-1 proviral load are features of HAM/TSP, but the immunological basis of IDH has not been established. In addition to severe cutaneous manifestations, the importance of IDH relies on the observation that up to 30% of children with IDH develop HAM/TSP in childhood and adolescence. In this study we determined the immune response in patients with IDH measuring interleukin (IL)-4, IL-5, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha levels as well as the HTLV-1 proviral load. Additionally, regulatory cytokines and anti-cytokines were added to cultures to evaluate the ability of these molecules to down-modulate TNF-alpha and IFN-gamma synthesis. HTLV-1 carriers and patients with HAM/TSP served as controls. TNF-alpha and IFN-gamma levels were higher in IDH than in HTLV-1 carriers. There was no difference in IFN-gamma and TNF-alpha concentrations in IDH and HAM/TSP patients. There was a tendency for higher IL-4 mRNA expression and immunoglobulin E (IgE) levels in IDH than in HTLV-1 carriers, but the difference did not reach statistical significance. The HTLV-1 proviral load was significantly higher in IDH patients than in HTLV-1 carriers. IDH is characterized by an exaggerated Th1 immune response and high HTLV-1 proviral load. The similarities between the immunological response in patients with IDH and HAM/TSP and the high proviral load observed in IDH provide support that IDH is a risk factor for development of HAM/TSP.

Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior.

Obesity is frequently associated with consumption of high amounts of sugar and/or fat. Studies have demonstrated a high prevalence of overweight and obesity associated or not with increase rates of psychiatry disorders, in particular mood and anxiety disorders. Recent works have demonstrated an association between specific genes involved in oxidative stress metabolism and anxiety-like behavior. The aim of this study was to investigate the effect of a highly palatable diet enriched with sucrose in body fat mass composition, anxiety behavior and brain oxidative status. Twenty male Wistar rats received two different diets during four months: standard chow (SC) and highly palatable (HP). Metabolic parameters, behavioral tests and oxidative stress status were evaluated. Body fat mass, insulin sensitivity and glucose tolerance were altered in the HP group (p<0.01). The same group spends less time in light compartment and had a lower risk assessment behavior (p<0.05) but no differences were observed in the open field test habituation (p>0.05). Protein degradation, DCF and TBARS levels were not different in the hippocampus between groups; however, there were higher levels of protein degration in frontal cortex of HP groups (p<0.05), although DCF and TBARS levels don't differ from the SC group (p>0.05). In conclusion, our data suggest that the consumption of HP diet leads to an obese phenotype, increases protein oxidation in frontal cortex and appears to induce anxiety-like behavior in rats.

Antioxidant activities of Ptychopetalum olacoides ("muirapuama") in mice brain.

Ptychopetalum olacoides (PO) roots are used by Amazonian peoples to prepare traditional remedies for treating various central nervous system conditions in which free radicals are likely to be implicated. Following the identification of PO ethanol extract (POEE) free-radical scavenging properties in vitro, the aim of this study was to verify the in vivo antioxidant effect of POEE. Aging mice (14 months) were treated (i.p.) with saline, DMSO (20%) or POEE (100mg/kg body wt.), and the hippocampi, cerebral cortex, striata, hypothalamus and cerebellum dissected out 60 min later to measure antioxidant enzyme activities, free-radical production and damage to macromolecules. POEE administration reduced free-radical production in the hypothalamus, lead to significant decrease in lipid peroxidation in the cerebral cortex, striatum and hypothalamus, as well as in the carbonyl content in cerebellum and striatum. In terms of antioxidant enzymes, catalase activity was increased in the cortex, striatum, cerebellum and hippocampus, while glutathione peroxidase activity was increased in the hippocampus. This study suggests that POEE contains compounds able to improve the cellular antioxidant network efficacy in the brain, ultimately reducing the damage caused by oxidative stress.

Antimicrobial resistance of Escherichia coli strains causing community-acquired urinary tract infections among insured and uninsured populations in a large urban center.

We assessed the susceptibility of Escherichia coli strains causing communityacquired urinary tract infection (UTI) in a large urban center in Brazil, comparing two different populations (patients with health insurance vs. uninsured). 581 nonduplicate strains of E. coli were isolated. The prevalence of antimicrobial resistance was greater than 20% for ampicillin (51%), trimethoprim-sulfamethoxazole (43%), tetracycline (41%) and chloramphenicol (22%). Overall, 12% of the E. coli isolates were resistant to ciprofloxacin. Resistance prevalences to most antimicrobials were similar in the two study populations. Our data provide much needed information on the prevalence of antimicrobial resistance among E. coli causing communityacquired UTI in Brazil. Antimicrobial resistance among strains of E. coli causing community-acquired UTIs was relatively high, particularly resistance to ciprofloxacin.

Toxoplasma gondii myelitis in a patient with adult T-cell leukemia-lymphoma.

Adult T cell leukemia-lymphoma (ATL) caused by HTLV-I may be associated with severe immunosupression and several opportunistic infections. Toxoplasmic encephalitis is a common central nervous system opportunistic infection in severely immunosupressed patients, however spinal cord involvement by this parasite is rare. In this paper, we report a case of toxoplasmic myelitis in a patient with ATL.

Prevalência de nódulos de tireóide detectados por ecografia em mulheres após os 40 anos / Prevalence of thyroid nodules in 40 years-old or old women

Nódulos de tireóide säo uma condiçäo clínica comum e em seu diagnóstico diferencial inclui-se o câncer de tireóide. Como o câncer de tireóide é raro, é importante conhecer a prevalência de nódulos de tireóide em grupos fortemente pre-dispostos para dimensionar seu impacto e adequar estratégias diagnósticas. OBJETIVOS: O objetivo deste estudo foi verificar a prevalência de nódulos de tireóide diagnosticados por ecografia em mulheres na maturidade. MÉTODOS: Entre agosto de 1996 e dezembro de 1997 foram avaliadas, de forma consecutiva, pacientes do sexo feminino com idade de 40 anos ou mais que realizavam ecografia no Serviço de Radiologia do HCPA...

[Prevalence of thyroid nodules in 40 years-old or old women]. / Prevalência de nódulos de tireóide detectados por ecografia em mulheres após os 40 anos.

OBJECTIVES: Thyroid nodules constitute a very common clinical problem and the differential diagnosis includes thyroid cancer. As thyroid cancer is rare, it is important to know the prevalence of thyroid nodules in cohorts strongly predisposed to this problem to be able to measure its impact on the health care system, and to devise appropriate diagnostic strategies. The aim of this study was to determine the prevalence of thyroid nodules in women 40 year-old or older by echography. METHODS: Between August 1996 and December 1997, 207 women, 40 year-old or older, were consecutively evaluated by thyroid echography in the Radiology Division of the Hospital de Clínicas de Porto Alegre. Patients who came to the Division to be submitted to thyroid echography were excluded. The mean age of patients studied was 54.7 years (median: 53, range: 40-86 years). One hundred and twenty three patients (54.9%) had a normal thyroid and eighty-two had an abnormal gland (39.6%). Thyroid nodules were detected in seventy-three women (35.3%) and these were larger than 1 cm in 35 women (16.9%). Women without thyroid nodules were younger (53.1 +/-10.7 years) than women with thyroid nodules (58.2 +/-10.6 years) p=0.001; and the prevalence of any thyroid nodule (p=0.001) or nodules larger than 1 cm (p=0.007) increased with age. CONCLUSIONS: Thyroid nodules are very common in women 40 year-old or older, their prevalence increases with age in this cohort and these nodules are potentially palpable (larger than one cm) in one of six women in this age group It is important to have these data in mind when ordering thyroid echographic studies in women 40 year-old or older.

The evolution of metropolitan spaces in Brazil.

"... The purpose of this paper is to show briefly the demographic differences and similarities in the evolution of the metropolitan spaces in Brazil, from 1940 to 1980." The data are from official sources. Extensive statistical data are included in appendixes.