Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. It is currently the most common chronic liver disease with complex pathogenesis and challenging treatment. Here, we investigated the hepatoprotective role of green tea (GT) and determined the involvement of miRNAs and its mechanism of action. METHODS: Male C57Bl/6 mice were fed with a high-fat diet for 4 weeks. After this period, the animals received gavage with GT (500 mg/kg body weight) over 12 weeks (5 days/week). HepG2 cell lines were transfected with miR-34a or miR-194 mimetics and inhibitors to validate the in vivo results or were treated with TNF-α to evaluate miRNA regulation. RESULTS: GT supplementation protects against NAFLD development by altering lipid metabolism, increasing gene expression involved in triglycerides and fatty acid catabolism, and decreasing uptake and lipid accumulation. This phenotype was accompanied by miR-34a downregulation and an increase in their mRNA targets Sirt1, Pparα, and Insig2. GT upregulated hepatic miR-194 by inhibiting TNF-α action leading to a decrease in miR-194 target genes Hmgcs/Apoa5. CONCLUSION: Our study identified for the first time that the beneficial effects of GT in the liver can be due to the modulation of miRNAs, opening new perspectives for the treatment of NAFLD focusing on epigenetic regulation of miR-34a and miR-194 as green tea targets.

[Patterns of antidemential drug use in a group of patients from Colombia]. / Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.

INTRODUCTION: The benefits of pharmacological therapy with anti-dementia drugs are not yet fully demonstrated and there is even a lack of publications describing their use profile. The present work sought to determine the prescription patterns of anti-dementia drugs in a Colombian population. PATIENTS AND METHODS: Descriptive cross-sectional study. Through a systematized database of 3.5 million affiliates to the Colombian health system, patients with uninterrupted dispensing of anti-dementia drugs between August-October/2016 were selected. Sociodemographic, pharmacological and comedication variables were analyzed. The costs of the therapies were estimated from the reference price of the medicines. RESULTS: We identified 8372 patients with a mean age of 79.5 ± 8.7 years and 65.3% (n = 5471) were women. The most widely used medication was rivastigmine (69.6%), mainly in transdermal presentation, followed by memantine (31.4%). In general, the average dose administered per day was lower than the defined daily dose. Only 568 patients (6.7%) used combination therapy. 84.3% of patients (n = 7061) used some additional medication and 54.2% (n = 4535) had another neurologic medication. The cost per 1000 inhabitants/day of rivastigmine was 3.47 USD and for memantine 0.30 USD. CONCLUSION: Patients with anti-dementia drugs are using them at doses lower than those defined and they present an important frequency of comorbidities and comedications.

TITLE: Patrones de uso de farmacos antidemencia en un grupo de pacientes de Colombia.Introduccion. Los beneficios del manejo farmacologico con medicamentos antidemencia aun no estan del todo demostrados, e incluso hay carencia de trabajos que describan su perfil de utilizacion. El presente trabajo busco determinar los patrones de prescripcion de farmacos antidemencia en una poblacion de Colombia. Pacientes y metodos. Estudio descriptivo de corte transversal. Mediante una base de datos sistematizada de 3,5 millones de afiliados al sistema de salud colombiano, se selecciono a pacientes con dispensaciones ininterrumpidas de farmacos antidemencia entre agosto y octubre de 2016. Se analizaron variables sociodemograficas, farmacologicas y comedicaciones. Se estimaron los costes de las terapias a partir del precio de referencia de los medicamentos. Resultados. Se identifico a 8.372 pacientes con una edad media de 79,5 ± 8,7 años; el 65,3% (n = 5.471) fueron mujeres. El farmaco mas utilizado fue la rivastigmina (69,6%), principalmente en presentacion transdermica, seguida de la memantina (31,4%). En general, la dosis media administrada por dia fue inferior a la dosis diaria definida. Solamente 568 pacientes (6,7%) usaron terapia combinada. El 84,3% de los pacientes (n = 7.061) uso medicamentos para alguna comorbilidad y el 54,2% (n = 4.535) tenia otro neurofarmaco. El coste por 1.000 habitantes/dia de la rivastigmina fue de 3,47 dolares, y de la memantina, de 0,30 dolares. Conclusion. Los pacientes con medicamentos antidemencia los estan empleando en dosis inferiores a las definidas y presentan una importante frecuencia de comorbilidades y comedicaciones.

Drug utilisation study in patients receiving antiepileptic drugs in Colombia.

INTRODUCTION: This study examines the indications according to which antiepileptic drugs are prescribed and used in a population of patients enrolled in the Colombian national health system (SGSSS). METHODS: Retrospective cross-sectional study. From the pool of individuals in 34 Colombian cities who used antiepileptic drugs between 18 July, 2013 and 31 August, 2014 during a period of no less than 12 months, we obtained a random sample stratified by city. Socio-demographic, pharmacological and comorbidity variables were analysed. Continuous and categorical variables were compared, and logistic regression models were used. RESULTS: Our patient total was 373 patients, with 197 women (52.1%) and a mean age of 41.9 ± 21.7 years; 65.4% of the patients were treated with monotherapy. The most frequently used drugs were valproic acid (53.1%) and carbamazepine (33.2%). Epilepsy was the most frequent indication (n=178; 47.7%); however, 52.3% of the patients were prescribed antiepileptics for different indications, especially neuropathic pain (26.8%), affective disorders (14.2%) and migraine prophylaxis (12.3%). A total of 81 patients with epilepsy (46.6%) displayed good seizure control while another 25 (14.4%) had drug-resistant epilepsy. In the multivariate analysis, medication adherence was associated with a lower risk of treatment failure in patients with epilepsy (OR: 0.27; 95%CI, 0.11-0.67). CONCLUSIONS: In Colombia, antiepileptic drugs are being used for indications other than those originally intended. Monotherapy is the most commonly used treatment approach, together with the use of classic antiepileptic drugs.

Disruption of prion protein-HOP engagement impairs glioblastoma growth and cognitive decline and improves overall survival.

Glioblastomas (GBMs) are resistant to current therapy protocols and identification of molecules that target these tumors is crucial. Interaction of secreted heat-shock protein 70 (Hsp70)-Hsp90-organizing protein (HOP) with cellular prion protein (PrP(C)) triggers a large number of trophic effects in the nervous system. We found that both PrP(C) and HOP are highly expressed in human GBM samples relative to non-tumoral tissue or astrocytoma grades I-III. High levels of PrP(C) and HOP were associated with greater GBM proliferation and lower patient survival. HOP-PrP(C) binding increased GBM proliferation in vitro via phosphatidylinositide 3-kinase and extracellular-signal-regulated kinase pathways, and a HOP peptide mimicking the PrP(C) binding site (HOP230-245) abrogates this effect. PrP(C) knockdown impaired tumor growth and increased survival of mice with tumors. In mice, intratumor delivery of HOP230-245 peptide impaired proliferation and promoted apoptosis of GBM cells. In addition, treatment with HOP230-245 peptide inhibited tumor growth, maintained cognitive performance and improved survival. Thus, together, the present results indicate that interfering with PrP(C)-HOP engagement is a promising approach for GBM therapy.

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases.

The sentinel lymph node (SLN) is considered to be the first axillary node that contains malignant cells in metastatic breast tumors, and its positivity is currently used in clinical practice as an indication for axillary lymph node dissection. Therefore, accurate evaluation of the SLN for the presence of breast metastatic cells is essential. The main aim of our study is to characterize the genomic changes present in the SLN metastatic samples with the ultimate goal of improving the predictive value of SLN evaluation. Twenty paired samples of SLN metastases and their corresponding primary breast tumors (PBT) were investigated for DNA copy number changes using comparative genomic hybridization (CGH). Non-random DNA copy number changes were observed in all the lesions analyzed, with gains being more common than losses. In 75% of the cases there was at least one change common to both PBT and SLN. The most frequent changes detected in both lesions were gains of 1pter-->p32, 16, 17, 19, and 20 and losses of 6q13-->q23 and 13q13-->q32. In the PBT group, alterations on chromosomes 1, 16, and 20 were the most frequent, whereas chromosomes 1, 6, and 19 were the ones with the highest number of changes in the SLN metastatic group. A positive correlation was found between the DNA copy number changes per chromosome in each of the groups. Our findings indicate the presence of significant DNA copy number changes in the SLN metastatic lesions that could be used in the future as additional markers to improve the predictive value of SLN biopsy procedure.

Intracranial hemorrhage following bone marrow transplantation: an autopsy study of 58 patients.

Autopsy files of 180 patients were reviewed, who died after BMT between July 1987 and June 1998 and 58 (32.2%) cases, who had experienced intracranial hemorrhage (ICH) were selected. Age, sex, underlying disease, preparatory regimens, immunoprophylaxis, chronic and acute GVHD, survival of the patients and localization and size of hemorrhages were evaluated. There were 33 males and 25 females, with a mean age of 23.4 years. The main underlying disorders for which BMT was performed included SAA (n = 21), CML (n = 13) and AML (n = 10). Forty patients were found to have intraparenchymal hemorrhage, 35 had subarachnoid hemorrhage and eight patients had subdural hemorrhage. In 16 cases the CNS hemorrhage was so extensive that it was considered to be the main cause of death. There was no significant statistical difference concerning sex (P = 0.217), age (P = 0.296), underlying disease (P= 0.352), preparatory regimens (P = 0.07), immunoprophylaxis (P = 0.914), chronic and acute graft-versus-host disease (P = 0.107 and P = 0.631, respectively) and survival (P = 0.701) when comparing patients with or without ICH. However, the number of cases in which the CNS was defined as the main cause of death was higher among patients with ICH than in patients without ICH (n = 16 vs 15) (P = 0.011). We conclude that ICH is common and has a significant mortality rate following BMT.

[Holoprosencephaly: morphological aspects of twelve cases of autopsy]. / Holoprosencefalia: análise do seu espectro morfológico em doze casos de autópsia.

The term holoprosencephaly (HPC) is used to indicate the group of hemispheric deformities caused by a failure in the development of the prosencephalic vesicle. The purpose of this study is to explain the morphologic spector of twelve cases of HPC, qualify them, and compare them to the literature. It was evaluated 5837 pediatrics necropsies, and there were 12 cases of HPC. Data like gender, age and the presence of another associated malformations were evaluated and compared to another malformations and to the total number of necropsies. The majority of the cases was male (66.66%), and stillborns (75%). The most frequently type of HPC found was the lobar type (58.3%), and the most frequently type of facial alteration was the ciclopy (25%). There is a statistic tendency to HPC affect the male sex, in comparison with other neurologic malformations. Besides, the stillborns are more frequently observed in HPC than in other neurologic malformations.

[Cerebrovascular diseases in patients aged 15 to 40 years: neuropathological findings in 47 cases]. / Doenças cerebrovasculares em pacientes entre 15 e 40 anos: achados neuropatológicos em 47 casos.

Cerebrovascular diseases in patients between 15 and 40 years old are not a frequent subject in Latin-American literature, especially when focusing on neuropathology. We analyzed 47 brains from necropsies performed from 1987 to 1997 and selected on a basis of age and the presence of vascular pathology. From the 47 analyzed brains, 26 belonged to females (55.3%). When distributed among age groups, 12.8% (n=6) affected patients from 15 to 20 yo, 51,1% (n=24) from 21 to 30 yo, 36,2% (n=17) from 31 to 40 yo. The underlying diseases were: cardiac and haemathologic (19.2%), pregnancy complications (12.76%), infections, diseases of blood vessels and neurological (10.1% each) amongst others. The neuropathological abnormalities included cerebral and/or cerebellar herniation (16%), cerebral edema (13.8%), subarachnoid hemorrhage (10%), recent cerebral infarction (9%), intraparenchymatous hemorrhage (8.14%), hypoxic-ischemic encephalopathy (3%) and other events such as Sneddon syndrome and Lupus vasculitis. These findings express that the cerebrovascular phenomena in this age group are unique and closely related with the underlying disease.

[Meningiomas in pediatric patients: report of 2 cases]. / Meningiomas em pacientes pediátricos: relato de 2 casos.

Meningiomas correspond to 1% - 4% of primary intracranial tumors in pediatric group, with their incidence raising according to age. There is not gender prevalence, in spite of some authors describe a male tendency opposed to female one in adulthood. At present study we describe two cases of pediatric meningiomas reviewing clinical, radiological and histological aspects of these lesions. The authors review also treatment options and prognosis of childhood meningiomas. A two-year-old boy was admitted with seizures. Computerized tomography showed a right parietal lesion, which was totally resected. Histological features were compatible with meningioma. After 17 months the child is doing well, with no deficits or seizures. The second case is a 12-year-old girl, with a headache complain. During investigation, a CT revealed a right frontal lesion. She was operated under a right frontal craniotomy with total tumor resection. Nowadays she is asymptomatic, 20 months after surgery. Despite meningiomas in pediatric group are uncommon; they should be included in differential diagnosis list of expansive intracranial lesions of childhood.

[Uncommon presentation of central neurocytoma causing intraventricular hemorrhage: case report]. / Neurocitoma central com apresentação incomum por hemorragia intraventricular: relato de caso.

Central neurocytoma was first described by Hassoun et al. in 1982 as a well-differentiated tumor from neuronal origin. This tumor typically occurs in young adults, localized in the ventricular system. It usually presents as intracranial hypertension due to obstructive hydrocephalus. The differential diagnosis should be done with others intraventricular tumors as oligodendroglioma, subependymoma and choroidal plexus papilloma. There are few cases of central neurocytoma presented by intraventricular hemorrhage in the literature. We report a case of 35 year-old woman, who presented with obstructive hydrocephalus due to intraventricular hemorrhage within the tumor. MRI revealed a tumor localized in the right lateral ventricle. Histopathological and immunohystochemical analysis confirmed the diagnosis of central neurocytoma. We review options for the treatment of this entity as well reinforce the inclusion of central neurocytoma as a differential diagnosis for intraventricular hemorrhage.

April 2001: a 70 year old woman with recurrent meningioma.

The April Case of the Month (COM). The contributors report a case of a 70 year-old woman with recurrent meningiomas, one of which showed rhabdoid and lipomatous differentiation. Histopathological study of the first and second previous resections showed only typical meningothelial meningioma. On the third craniotomy, a new tumor specimen showed an admixture of classic meningothelial meningioma with lipomatous and rhabdoid foci. Immunohistochemical studies showed diffuse reactivity for epithelial membrane antigen and vimentin, as well as focal positivity for desmin and smooth muscle actin in the areas with rhabdoid features and S100 protein in the lipomatous foci. The presence of these three different and concomitant histological patterns only in the third surgical resection might support a metaplastic origin and, also, corroborates the concept that rhabdoid features are suggestive of an aggressive behavior.

[The neuropathology of neonatal period: analysis of 1616 autopsies]. / A neuropatologia no período neonatal: análise de 1616 casos de necropsia.

The lesions of the central nervous system represent an important cause of morbid-mortality in the neonatal period. This is due to the vulnerability of the brain to several adverse conditions during gestation and after birth. This study analyses the prevalence and pattern of central nervous system lesions in neonates autopsied at Hospital de Clínicas - Curitiba. There were 5743 pediatric autopsies performed in the Sector of Anatomic Pathology from 1960 to 1995 with 2049 cases corresponding to death during neonatal period. These later autopsies were reviewed and all cases with central nervous system lesions were selected and classified according to sex, age and pattern of central nervous system lesion. The central nervous system was affected in 1616 (78,87%) of neonatal autopsies and there was predominance of intracerebral hemorrhages (73,39%), congenital malformations (4,27%) and infections (3,59%). The hypoxic hemorrhages are the most prevalent central nervous system lesions in the neonatal period, affecting mainly premature babies. There was predominance of central nervous system malformations in the female neonates.

[Spinal cord ganglioglioma: case report]. / Ganglioglioma da medula espinhal: relato de caso.

Gangliogliomas are rare tumors of the CNS, representing only 2.7-3.8% of primary tumors of the CNS, and the intramedullary location accounts 7.6-14.3% of cases. The main goal of treatment is the total resection, preserving as much as possible the patients neurological function. Adjuvant therapy as radiotherapy is reserved to cases of progression of disease after surgery or in such lesion with more aggressive biological behavior. In this article we report the case of a patient with a intramedullary ganglioglioma involving spinal levels T5 to T10, who was operated in our service, and we review the literature analyzing various aspects, including the modalities of treatment which can be used in this kind of lesion.

Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases.

Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11-year period at our institution. The incidence of T. gondii infection in our institution (1.14 per 100 allogeneic BMT) is higher than previously reported. The most frequently affected sites were the brain, lungs, and heart. Findings common to most patients who developed toxoplasmosis were positive pre-transplant serology, allogeneic transplant and graft-versus-host disease and its treatment, as well as BMT from matched unrelated donors. All 9 patients died and 8 were diagnosed only after autopsy. Heightened awareness of the occurrence of toxoplasmosis in marrow recipients, especially in highly endemic areas, and early diagnosis and therapy are needed for a better outcome.

Accuracy of the smear technique in the cytological diagnosis of 650 lesions of the central nervous system.

The authors analyzed the results of 650 lesions of the central nervous system submitted to intraoperative cytological diagnosis by the smear technique. Cytological and paraffin section diagnoses were compared. The following statistical values were obtained: accuracy of 97.3%, sensitivity of 97.9%, specificity of 95%, positive predictive value of 99.1%, and negative predictive value of 89.6%. The authors comment on their main pitfalls using this cytological diagnostic procedure.

Peritoneal effusion in a dog secondary to visceral mast cell tumor. A case report.

BACKGROUND: Mast cell tumor, one of the most common skin tumors in dogs, may also be found in visceral sites (mainly spleen and liver). When a visceral mast cell tumor is present, neoplastic mast cells may be found in any effusion secondary to the tumor. Therefore, the diagnosis may be made by cytologic analysis of the effusion. CASE: An 8-year-old, spayed, female Siberian husky presented with a peritoneal effusion secondary to a visceral mast cell tumor. Seven months earlier, the dog had presented with a cutaneous nodule diagnosed as a well-differentiated mast cell tumor. The peritoneal fluid was classified as a transudate. Numerous neoplastic mast cells were found in the effusion. Although the mast cell tumor presented with characteristics of the well-differentiated tumor, its biologic behavior was that of a malignant tumor. CONCLUSION: Care should be taken to evaluate the prognosis of mast cell tumors in dogs since their biologic behavior is extremely variable.

[Clinical practice guidelines of the Spanish Society of Cardiology for surgical risk assessment in cardial patients treated with non-cardiac surgery]. / Guías de práctica clínica de la Sociedad Española de Cardiología en la valoración del riesgo quirúrgico del paciente cardiópata sometido a cirugía no cardíaca.

All patients undergoing a surgical intervention require a cardiovascular evaluation that establishes the surgical risk. On the other hand, an important proportion of the deaths that happened during the surgery are due to cardiovascular complications, many of them could be avoided with a cardiac risk screening. The surgery and the anesthesia subject the patient to stress situations during the perioperative period that forces the check upon capacity of the patient to respond to those demands, dissuading surgery if it considered that the risk is very high. The rate of major surgery in elderly patients is growing, with the increase in cardiovascular complications, mainly myocardial infarction, unstable angina and perioperative heart failure. Following we establish some recommendations for the cardiovascular assessment of the cardiac patient that will undergo noncardiac surgery.

Pleomorphic xanthoastrocytoma: report of a case diagnosed by intraoperative cytopathological examination.

The authors present an unusual case of a 13-yr-old boy with a 3-mo history of seizures. A CT scan showed a contrast-enhancing mass located in the left temporal lobe. The patient underwent a stereotatic-guided craniotomy; intraoperative cytological diagnosis was performed by the smear technique, showing a pleomorphic xanthoastrocytoma. The tumor was totally resected. Definitive diagnosis was established by examination of paraffin-embedded material. Six months after the surgical intervention, the patient is doing well, with no radiological evidence of recurrence. The cytological differential diagnosis of giant cell lesions of the central nervous system is emphasized.