Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats.

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective ß3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1ß, and IL-6 gene expression and IL-1ß and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Brain glucose hypometabolism and hippocampal inflammation in Goto-Kakizaki rats

Brain glucose hypometabolism and neuroinflammation are early pathogenic manifestations in neurological disorders. Neuroinflammation may also disrupt leptin signaling, an adipokine that centrally regulates appetite and energy balance by acting on the hypothalamus and exerting neuroprotection in the hippocampus. The Goto-Kakizaki (GK) rat is a non-obese type 2 diabetes mellitus (T2DM) animal model used to investigate diabetes-associated molecular mechanisms without obesity jeopardizing effects. Wistar and GK rats received the maintenance adult rodent diet. Also, an additional control group of Wistar rats received a high-fat and high-sugar diet (HFHS) provided by free consumption of condensed milk. All diets and water were provided ad libitum for eight weeks. Brain glucose uptake was evaluated by 2-deoxy-2-[fluorine-18] fluoro-D-glucose under basal (saline administration) or stimulated (CL316,243, a selective β3-AR agonist) conditions. The animals were fasted for 10-12 h, anesthetized, and euthanized. The brain was quickly dissected, and the hippocampal area was sectioned and stored at -80°C in different tubes for protein and RNA analyses on the same animal. GK rats exhibited attenuated brain glucose uptake compared to Wistar animals and the HFHS group under basal conditions. Also, the hippocampus of GK rats displayed upregulated leptin receptor, IL-1β, and IL-6 gene expression and IL-1β and the subunit of the transcription factor NF-κB (p-p65) protein expression. No significant alterations were detected in the hippocampus of HFHS rats. Our data indicated that a genetic predisposition to T2DM has significant brain deteriorating features, including brain glucose hypometabolism, neuroinflammation, and leptin signaling disruption in the hippocampal area.

Dental age assessment by the pulp/tooth area proportion in cone beam computed tomography: is medico-legal application for age estimation reliable?

INTRODUCTION: Forensic dentistry has, as one of its main goals, the identification of living and/or deceased individuals, based on the individual features of the teeth. One of the identification criteria to be established is the chronological age. Several authors, including Kvaal, have developed age estimation methods based on secondary dentine deposition. Nowadays, three-dimensional imaging tests, such as Cone Beam Computed Tomography (CBCT), are used in age estimation. OBJECTIVE: The aims of this research project were to validate Kvaal's method and its variables in age estimation and to create new linear regression formulae to better represent the study sample. METHODS: We selected 158 CBCT, with a total of 402 sound teeth (central incisors, lateral incisors and canines). The necessary measurements and ratios were calculated in both coronal and sagittal sections, with XelisDental . The formulae developed by Kvaal for age estimation calculation were applied. Subsequently, the results were statistically analyzed. RESULTS AND DISCUSSION: The intraclass correlation coefficients from the two measurements ranged from 0.918 to 0.997. The calculated age estimation had a mean error of -21.4years (coronal section) and -26.3years (sagittal section). The t test revealed statistically significant differences between chronological age and estimated age. The absolute values of Pearson's correlation coefficient between age and the two Kvaal variables ranged from 0.06 to 0.38 and from 0.06 to 0.55. The coefficients of determination are lower than in the original study (between 0.03 and 0.39). In the linear regression formulae, the coefficients of determination ranged from 0.07 to 0.41. CONCLUSION: This investigation concludes a non-reproducibility of Kvaal's method in the Portuguese population when applied in CBCT, with statistically significant differences between the chronological age and the dental age, estimated by the pulp/ tooth proportion method, based on the teeth analyzed in this study.

Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer

Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.

Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer.

Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.

Omega-3 fatty acids differentially modulate enzymatic anti-oxidant systems in skeletal muscle cells.

During physical activity, increased reactive oxygen species production occurs, which can lead to cell damage and in a decline of individual's performance and health. The use of omega-3 polyunsaturated fatty acids as a supplement to protect the immune system has been increasing; however, their possible benefit to the anti-oxidant system is not well described. Thus, the aim of this study was to evaluate whether the omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) can be beneficial to the anti-oxidant system in cultured skeletal muscle cells. C2C12 myocytes were differentiated and treated with either eicosapentaenoic acid or docosahexaenoic acid for 24 h. Superoxide content was quantified using the dihydroethidine oxidation method and superoxide dismutase, catalase, and glutathione peroxidase activity, and expression was quantified. We observed that the docosahexaenoic fatty acids caused an increase in superoxide production. Eicosapentaenoic acid induced catalase activity, while docosahexaenoic acid suppressed superoxide dismutase activity. In addition, we found an increased protein expression of the total manganese superoxide dismutase and catalase enzymes when cells were treated with eicosapentaenoic acid. Taken together, these data indicate that the use of eicosapentaenoic acid may present both acute and chronic benefits; however, the treatment with DHA may not be beneficial to muscle cells.

Lewis histo-blood group system phenotyping and genotyping reveal divergence in the association of Le(a-b-) phenotype and type 1 diabetes.

BACKGROUND AND OBJECTIVES: The red blood cell Le(a-b-) phenotype was proposed as risk factor for type 1 diabetes, but contradictory results were published elsewhere. This study re-examined the potential association between Lewis histo-blood group system and type 1 diabetes. MATERIAL AND METHODS: Patients and controls of both sexes, Caucasians and non-Caucasians, matched by sex, geographical origin and ethnicity were evaluated. The red blood cell Lewis phenotypes were identified by gel column agglutination and also inferred from the FUT2 and FUT3 genotyping. RESULTS: The Le(a-b-) phenotype was prevalent in patients with type 1 diabetes, and the Le(a-b+) phenotype was prevalent in controls when both were determined by gel columns agglutination. No differences were observed in the frequencies of the Le(a-b-) phenotype inferred from the FUT2 and FUT3 genotyping between patients and controls. CONCLUSIONS: The Lewis red blood cell phenotyping and genotyping reveal divergence in the association of Le(a-b-) phenotype and type 1 diabetes.

Aspectos reprodutivos e produtivos de vacas da raça Holandesa com puerpério normal ou patológico / Reproductive and productive parameters of Holstein cows with normal or pathological puerperium

Foram avaliadas 103 vacas da raça Holandesa de primeira, segunda ou terceira ordens de lactação, com o objetivo de comparar aspectos reprodutivos e produtivos dos animais com puerpério normal ou patológico. Exames ginecológicos foram realizados semanalmente, do parto ao final do puerpério, por meio de palpação transretal, ultrassonografia e vaginoscopia. As incidências de partos gemelares, partos auxiliados, retenção de placenta e infecções uterinas até o primeiro serviço foram de 11,7%, 20,4%, 38,8% e 75%, respectivamente. A involução uterina e a primeira ovulação ocorreram aos 33,5±11,1 e 43,6±21,5 dias após o parto, respectivamente, com diferenças (P<0,001) entre vacas com ou sem infecção uterina. O primeiro serviço ocorreu aos 75,9±31,0 dias após o parto e a taxa de gestação foi de 20,7%. A produção de leite diária foi de 27,9±7,3 litros por vaca até 42 dias após o parto. O prejuízo com a redução na produtividade e o descarte do leite contaminado com resíduos de antibiótico foi equivalente a 598 litros de leite por vaca com retenção de placenta e infecção uterina. A alta incidência de transtornos puerperais interferiu na fertilidade e na produção de leite, causando elevado impacto econômico para a propriedade.

The study was performed with 103 Holstein cows of first, second or third orders of lactation, and aimed to compare reproductive and productive parameters of animals with normal or pathological puerperium. Uterine and ovarian examinations were performed weekly until 42 days after parturition, by rectal palpation, vaginoscopy and ultrasonography. The incidence of twin pregnancies, assisted births, retained placenta, and uterine infection until the first service, were 11.7%, 20.4%, 38.8% and 75%, respectively. Uterine involution and detection of the first corpus luteum occurred at 33.5±11.1 and 43.6±21.5 days after parturition, respectively, and differed (P<0.01) between cows with or without uterine infection. The first artificial insemination occurred in average at 75.9±31.0 days after parturition, and the pregnancy rate was 20.7%. Average daily milk yield was 27.9±7.3 liters/cow until 42 days after parturition. Financial losses related to decreased milk production and discarding of milk contaminated with antibiotic residues corresponded to 598 liters of milk/cow presenting retained placenta and uterine infection. The high incidence of puerperal diseases negatively affected the fertility and milk production, causing large economic impact to the milk production system.

The effect of glutamine supplementation and physical exercise on neutrophil function.

Glutamine is the most abundant free amino acid in the body. Its primary source is skeletal muscle, from where it is released into the bloodstream and transported to a variety of tissues. Several studies have shown that glutamine is important for rat and human neutrophil function and that these cells utilize glutamine at high rates. Physical exercise has also been shown to induce considerable changes in neutrophil metabolism and function. As neutrophils represent 50-60% of the total circulating leukocyte pool and play a key role in inflammation, both physical exercise and glutamine might be expected to regulate the inflammatory process. In this review, the changes in neutrophil function induced by physical exercise and glutamine supplementation are compared.

Assessment of takotsubo (ampulla) cardiomyopathy using iodine-123 metaiodobenzylguanidine scintigraphy.

PURPOSE: To evaluate the role of cardiac sympathetic innervation in patients whose clinical features consisted of chest pain, transient ST-segment elevation, left ventricular apical akinesis, minimal elevation of cardiac enzymes, and onset of symptoms shortly after a severe stress condition. MATERIAL AND METHODS: Five female patients, mean age 67+/-14 years, underwent thoracic 123I-MIBG (planar and SPECT) and 67Ga citrate (planar) scans within 5 days after the onset of symptoms. The 123I-MIBG myocardial washout rate between early (30 min) and delayed (3 hours) planar images was calculated. All patients presented findings consistent with takotsubo-like syndrome. Echocardiograms showed the characteristic wall motion pattern of significant apical dysfunction. Acute-phase coronary angiographies revealed a non-obstructive pattern. A peculiar apical akinesis and basal normokinesis were observed on the ventriculograms. RESULTS: Impairment of cardiac neuronal uptake of 123I-MIBG based on a reduction of the heart-to-mediastinum uptake ratio was observed in all patients, while the washout rate was raised in four patients. All patients presented an apical uptake defect in the 123I-MIBG SPECT and planar images and a normal 67Ga scintigraphy. CONCLUSION: Our data indicate that ampulla cardiomyopathy (AC) is associated with a cardiac sympathetic innervation deficit characterized by a reduced global 123I-MIBG uptake and an apical uptake defect. The lack of 67Ga uptake in the acute phase of this syndrome indicates that AC is probably not associated with an inflammatory process.

Utilização de prótese endovascular em aneurisma roto de aorta torácica / Endovascular protese in broken aneurysm of thoracic aorta

Os autores relatam caso cirúrgico de paciente com aneurisma roto da aorta descendente, em tratamento de neoplasia de colon e submetido ao tratamento com implante de prótese endovascular com êxito.

Bovine pericardium used as a cardiovascular patch.

BACKGROUND: The use of glutaraldehyde preserved bovine pericardium in valvular prostheses is well known. Although widely used clinically as patch material, bovine pericardium has not been extensively studied in this setting. METHODS: With this objective, 21 dogs received a standard bovine pericardial patch to partially replace the aortic, left atrial, or pericardial walls. The dogs were randomly divided into three groups according to implant duration. Group 1 consisted of 6 dogs evaluated surgically after 33 to 43 postoperative days, Group 2 with 7 dogs reoperated after 120 to 165 days, and Group 3 with 8 dogs reoperated after 225 to 305 days. RESULTS: Microscopic and macroscopic evaluation demonstrated: 1) the wrinkled surface of the bovine pericardium adhered to neighboring structures whereas the smooth surface did not adhere to the epicardium; 2) the bovine pericardial patch did not show structural changes in any of the implant sites; 3) the final left atrial patch was significantly smaller than the aortic and pericardial patches for Group 2 and Group 3 dogs; 4) the atrial patch area decreased significantly, whereas the aortic and pericardial areas did not change over time; 5) the pericardial implant was significantly thinner than the aortic and left atrial patches for Group 3 dogs; 6) a layer of fibrous connective tissue was formed on the smooth surface of the left atrial and aortic patches. The internal apposition fibrasis was significantly thicker in the left atrium than in the aorta in Groups 1 and 2; 7) the internal fibrasis layer of the atrial and aortic patches was calcified in Groups 2 and 3; and 8) the internal apposition tissue of the atrial and aortic patches showed neoformation of elastic fibers which clearly increased with implant duration. CONCLUSIONS: The fate of implanted glutaraldehyde-preserved bovine pericardial patches in cardiovascular applications depends on three factors: 1) the contact surface, 2) the tension it is subjected to, and 3) contact with blood flow.

The heterogeneity of the beta s cluster haplotypes in Brazil.

The beta s cluster haplotypes were determined for 74 Brazilian patients with sickle cell anemia from three cities separated by 1,400 to 2,300 km. The cities are representative of the regions which have the largest Black populations of the country. All 138 chromosomes with typical haplotypes had one of the three most common African haplotypes. No example of the Asian or of the Cameroon haplotypes was found. The Bantu haplotype predominates in all three regions (54.8 to 73.1%), followed by the Benin haplotype (25.4 to 45.2%) and a small number of cases with the Senegal haplotype (0 to 6.9%). The mean prevalence of the Bantu haplotype of 65.9% agrees closely with historical data which indicate that 70% of the African slaves brought to Brazil originated from regions of Bantu populations.

Avaliacao da funcao adrenal em tuberculosos. Estudo da resposta adrenal ao estimulo rapido com ACTH com dosagens de cortisol serico. / Adrenal function evaluation in tuberculosis study of adrenal response to rapid ACTH stimulation with dosages of serum cortisol

Por meio de estimulo rapido com ACTH, os autores analisam 23 pacientes recem-diagnosticados de tuberculose e 11 pacientes tratados de tuberculose e, como controle, 19 individuos normais. Esses tres grupos apresentam incremento absoluto de cortisol (microg/dl) de 7,6+/-4,2, 10,5+/-4,7 e 11,3+/-5,8, respectivamente. O incremento subnormal dos pacientes recem-diagnosticados e significativamente menor que o grupo-controle, mas o incremento dos pacientes tratados e equivalente ao do grupo-controle. Com estes dados, os autores recomendam maior atencao quanto a fisiologia adrenal nos pacientes recem-diagnosticados e tratados de tuberculose