SOMATIC DEFICIENT MISMATCH REPAIR ASSESSED BY IMMUNOHISTOCHEMISTRY AND CLINICAL FEATURES IN BRAZILIAN GLIOBLASTOMA PATIENTS.

BACKGROUND: Glioblastoma (GBM) is the most frequent primary malignant CNS tumor. Deficient mismatch repair (dMMR) is associated with better prognosis and is a biomarker for immunotherapy. Evaluation of MMR by immunohistochemistry (IHC) is accessible, cost effective, sensitive, and specific. AIM: Our objective was to investigate MMR proteins in adult GBM patients. MATERIALS AND METHODS: We retrospectively analyzed 68 GBM samples to evaluate the proficiency of MMR genes expression assessed by IHC. Clinicopathologic and molecular features were compared in proficient (pMMR) or dMMR. RESULTS: 10 (14.7%) samples showed dMMR, and the most frequent was MSH6 (100%) followed by MSH2, PMS2, and MLH1. We observed heterogeneous expression of dMMR in 5 GBMs. The median overall survival did not differ between pMMR (19.8 months; 0.2-30) and dMMR (16.9 months; 6.4-27.5) (p = 0.31). We observed a significantly higher overall survival associated with gross total resection compared to subtotal resection or biopsy (30.7 vs. 13.6 months, p = 0.02) and MGMT methylated status (29.6 vs. 19.8 months, p = 0.049). At the analysis time, 10 patients were still alive, all in the pMMR group. CONCLUSIONS: Our data demonstrated dMMR phenotype assessed by IHC in an expressive portion of GBM patients, however without significant impact on overall survival.

Breast cancer: the real road of the Brazilian northeast.

Objective: To characterize the clinical and sociodemographic aspects of breast cancer patients undergoing cancer treatment in the State of Maranhão, in a public reference hospital. Methods: Descriptive, correlational and analytical cross-sectional study, conducted between January 2019 and February 2020, at the Tarquínio Lopes Filho State Cancer Hospital. The study population consisted of all women, in first consultation, with breast cancer undergoing chemotherapy, in agreement with the study and with no brain metastasis evidenced. Statistical analysis was performed using SPSS v. 19 software, considering a significance level of 5%. Results: Eighty adult women were part of the study, whose average age was 52.54. Most of the women were born in São Luís, white, housewives, sedentary, married, former smokers, and Catholic. They had technical/specialized training. In the clinical results, the histological type of infiltrative ductal carcinoma predominated, as well as stage III, mastectomy and the doxorubicin-cyclophosphamide-taxol chemotherapy regimen. Conclusion: The knowledge of each regional profile assists health professionals regarding the characterization of a target population and the design of targeted preventive and self-care strategies by managers.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Immunohistochemical expression of types I and III collagen antibodies in the temporomandibular joint disc of human foetuses.

The objective was to study the morphology of the articular disc and analyse the immunohistochemical expression of types I and III collagen markers in the temporomandibular joint (TMJ) disc of human foetuses of different gestational ages. Twenty TMJ from human foetuses supplied by Universidade Federal de Uberaba with gestational ages from 17 to 24 weeks were studied. The gestational age of the foetuses was determined by measuring the crown-rump (CR) length. Macroscopically, the foetuses were fixed in 10% formalin solution and dissected by removing the skin and subcutaneous tissue and exposing the deep structures. Immunohistochemical markers of type I and III were used to characterize the existence of collagen fibres. Analysis of the immunohistochemical markers of types I and III collagen revealed the presence of heterotypical fibril networks.

Motor neuron disease associated with non-fluent rapidly progressive aphasia: case report and review of the literature.

The superimposed clinical features of motor neuron disease (MND) and frontotemporal lobar degeneration (FTLD) comprise a rare neurological overlap syndrome that represents a diagnostic challenge to neurologists. Currently, FTLD-MND is considered a distinct entity and its clinicopathological basis has recently been reviewed. Our aim is to present a patient with MND and non-fluent rapidly progressive aphasia with clinical, imaging and histopathological correlation, as well as a brief review of the literature. We demonstrated the selective corticospinal tract (CST) and temporal lobe involvement using T1 spin-echo with an additional magnetization transfer contrast pulse on resonance (T1 SE/MTC) and FLAIR MR sequences in our patient, with further clinical and histopathological correlation. To the best of our knowledge, there is no description about the use of these particular MR sequences in the evaluation of FTLD-MND patients.

Sleep patterns over 15-day period in rats with spinal cord injury.

STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: The purpose of this study was to evaluate over a 15-day period alterations in sleep pattern of rats after spinal cord injury (SCI). SETTING: Federal University of São Paulo, Department of Psychobiology. METHODS: In total, 20 male Wistar rats were used. The rats were divided in two groups: SHAM and SCI. The rats were submitted to the following procedures: electrode insertion surgery, 24 h duration baseline sleep recording, SCI (level T9) and subsequent sleep recording for 15 consecutive days. RESULTS: The results showed a reduction in sleep efficiency in the light period for Days 1-3, 5, 10 and 12 after SCI in relation to the SHAM group, with alterations in total waking time and sleep stages. Limb movements were observed 4 days after SCI. CONCLUSION: The present findings suggest that SCI may be heavily involved in altering sleep pattern in SCI subjects and that the inactivity caused by SCI may be exacerbating this altered sleep pattern.

Inhibin alpha-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers.

The R337H TP53 mutation is a low-penetrance molecular defect that predisposes to adrenocortical tumour (ACT) formation in Brazilian and possibly other populations. Additional genetic defects may be responsible for the variable expression of ACTs in these cases. The inhibin alpha-subunit gene (INHA) on 2q33-qter has been implicated in mouse adrenocortical tumourigenesis. We studied 46 pediatric patients with ACTs from Brazil for INHA genetic alterations; 39 of these patients were heterozygous carriers of the R337H TP53 mutation. We first mapped the INHA gene by radiation hybrid analysis and determined 10 linked microsatellite markers in an area flanked by D2S1371 and D2S206 on 2q33-qter. These markers were then used for loss of heterozygozity (LOH) studies in nine paired germline and tumour DNA samples. Mapping placed the INHA gene in close proximity to D2S2848 (SHGC11864) with a log of odds (LOD) score of 5.84. LOH for at least one marker in the region was identified in 8/9 tumours (89%). Six patients were heterozygous for three INHA mutations: one in exon 1, 127C>G, and two in exon 2, 3998G>A and 4088G>A, all leading to amino acid substitutions (P43A, G227R, and A257T, respectively). A257T is located in a conserved INHA region, highly homologous to transforming growth factor-beta; both G227R and A257T change polarity, and, in addition, G227R changes the pH. We conclude that these sequence alterations and the detected 2q allelic changes suggest that INHA may be one of the contributing factors needed for ACT formation in pediatric patient carriers of the R337H TP53 mutation.

Characterization of cellular phenotypes and cytokine expression in balt from children with congenital heart diseases.

UNLABELLED: The present study was performed to target and call attention to the bronchial associated lymphoid tissue (BALT), part of our immune system, from which, we believe, several forms of prophylactic and therapeutic approaches can be developed. The characterization of its immune components, cells, and cytokines, in absence of antigenic stimuli, is pioneer in literature. Eighteen cases of necropsies were chosen and selected the paraffin-embedded lungs. The ages of 11 females and 7 males varied from 5 to 31 months. Cause of death: congenital heart diseases. EXCLUSION CRITERIA: lung infection at necropsy and/or arterial hypertrophy greater than Heath-Edwards' 1st degree. Immunohistochemical technique was applied to identify the cell phenotypes and the cytokines in situ. BALT was identified in all cases in this study. The main cellular phenotypes in BALT were T helper (TH) and B lymphocytes surrounded by T cytotoxic lymphocytes, natural killer cells, and dendritic cells in less quantities. Interleukin 10 and Tumor Necrosis Factor alpha were the predominant cytokines in BALT without antigenic stimuli. BALT is an important structure of the lung immune system in infants, with a tendency to maintain an environment favorable to the Th2 arm of immune response. It needs more exploration to define its behavior in front of infections, especially those with pulmonary tropism.

"Gliomatosis cerebri" simulating an acute diffuse encephalomyelitis. Case report.

Neuroradiologic, neuropathologic and immunohistochemical features are reported in a young man with a impairment of the central nervous system mimicking an acute diffuse encephalomyelitis. A white male, 17 years old, healthy till 4 months before, when developed a right hemiparesis and after 2 months a bilateral hemiparesis with a progressive impairment of several cranial nerves. Magnetic resonance imaging showed multiple lesions without a mass effect that suggested myelin loss. He remained unconscious for almost one month before dying of pneumonia. The neuropathologic examination showed a heavy brain (1505 g) with herniations and a large right midbrain. There were several soft and pink areas mainly at the right midbrain, left cerebellum and in the white matter of the left cerebral hemisphere. The histopathologic sections showed diffuse blastomatous proliferation without total replacement or destruction of the original tissue. The tumor cells had astrocytic, oligodendrocytic and spongioblastic phenotypes, some of them with a GFAP-positive reactivity. There were focal anaplastic changes. The diagnosis of "gliomatosis cerebri" was only possible by the autopsy.

Central nervous system virion detection in acute measles: histophatological, ultrastructural and pathogenic aspects

Foram realizados estudos histopatologicos e ultraestruturais de 23 pacientes que morreram com diagnostico clinico de sarampo. Presenca de nucleocapsides virais foi pesquisada em 12 casos e detectada em 50 por cento destes casos no SNC. Eram, na maioria dos casos, intranucleares. As alteracoes histopatologicas associadas a manifestacoes neurologicas e a deteccao do virus sao discutidas em relacao as manifestacoes clinicas agudas e tardias.

Central nervous system virion detection in acute measles: histopathological, ultrastructural and pathogenetic aspects.

Histopathological and ultrastructural studies of 23 patients who died with clinical diagnosis of measles were carried out. In 12 cases viral nucleocapsids were searched by electron microscopy and detected in 100% of the cases in the lungs and in 50% of the cases in the central nervous system. They were mostly intranuclear. Histopathological changes associated to neurological alterations and the detection of virion are discussed in relation to acute and delayed clinical manifestations.

[Multiple sclerosis: clinical and pathological study of a case]. / Esclerose múltipla: estudo clínico e patológico de um caso.

We present a case with diagnosis of multiple sclerosis done on clinical criteria and proved by autopsy. The morphological aspects of the lesions are well known and often related in the literature. Our objective is to describe the first necropsy among 30500 done at Santa Casa de São Paulo in a patient with the disease. The morphological aspects in the CNS with the characteristic plaques in different grades of activity and the detection of immunoglobulins in these plaques confirm the pathogenic hypothesis about a disease immunologically mediated.

[Tumors of the brain stem: anatomo-pathologic study of 35 necropsy cases]. / Tumores do tronco cerebral: estudo anatomopatológico em 35 casos de necrópsia.

Brain stem tumors are rare and are usually treated without histological diagnosis. Its incidence varies in literature between 1.09% and 17.5% of all cerebral tumors. The objective of our study is to present a casuistic of these tumors in 28500 necropsies performed from 1952 till 1985 at the Department of Pathology, Santa Casa Hospital, São Paulo. We emphasize neuropathologic aspects, and compare our cases with those of other series. Also, we point out those tumors which are most frequent in this region, with the aim of possibly contributing to a better therapeutic approach. We used some clinical data and pathological diagnosis, and localized the tumor in the brain stem. Its microscopic diagnosis was determined according to the World Health Organization criterion. Among 428 intracranial tumors observed, 35 were localized in the brain stem. Intrinsic tumors and metastasis were included, and excluded those tumors which infiltrated the brain stem. Greatest incidence occurred in the first decade and cerebral edema was the predominant cause of death. Preferential topography was in the pons and the most frequent tumor was glioblastoma multiformis (19 cases). Metastasis ranked second (9 cases), being mostly from lungs. Some authors oppose tumor biopsy in this region because of high surgical risk. We do not agree with this opinion. We believe that the diagnosis of glioma is important to rule out the characteristics of malignancy. We can not leave without considering the diagnosis of other pathologies which can cause expansion in the brain stem. Therapeutical approach can be more adequate with the histological diagnosis of glioma or of other possibilities as shown here.

Cytoadherence in human falciparum malaria as a cause of respiratory distress.

The ultrastructure of three cases of fatal human falciparum malaria was studied in order to identify the cytoadherence of the endothelial cells in relation to parasitized red blood cells and septal interstitial changes which could be related to respiratory distress. Two cases showed marked endothelial oedema narrowing the capillary lumen with areas of adherence preferentially related to knobs, accompanied by septal interstitial oedema. One case showed no endothelial cells oedema, no knobs in parasitized red blood cells with no cytoadherence, no septal interstitial oedema and no respiratory distress. Cytoadherence seems to be the mechanism responsible for the septal pulmonary changes in severe falciparum malaria.

[Heidenhain's form of Creutzfeldt-Jakob disease: report of a case]. / Forma de Heidenhain da doença de Creutzfeldt-Jakob: relato de um caso.

A case of Creutzfeldt-Jakob disease, Heidenhain's form is reported. The first clinical manifestations were cortical blindness and visual agnosia. The patient here concerned, a woman aged sixty three, during the clinical course of the disease showed mental deterioration and pyramido-extrapyramidal manifestations. She died after five months. The electroencephalographic findings showed periodic activity. The anatomopathological examination showed neuronal degeneration, status spongiosus and proliferation of astroglial cells. The clinical, electroencephalographic, pathological and etiopathogenical aspects are discussed.

[Ganglioneuroma and chronic secretory diarrhea]. / Ganglioneuroma e diarréia crônica secretora.

The clinical case of a six year old child with two years of severe watery chronic diarrhea is presented. An exhaustive investigation followed by exploratory abdominal surgery, showed ganglioneuroma secreting tumor of VIP (vasoactive intestinal polypeptide). The clinical behavior, the complexity of the diagnostic, its rareness and its physiopathology are discussed.