Selective Vulnerability of Hippocampi for Nitric Oxide Synthases in Alzheimer's Disease Pathology and Cognitive Abilities.

Alzheimer's disease (AD) neuropathological changes (ADNC) are characterized by amyloid plaques and neurofibrillary tangles. The role of nitric oxide synthase (NOS) in disease progression remains unclear. This study investigates the expression of neural, inducible, and endothelial NOS (nNOS, iNOS, eNOS) and 3-nitrotyrosine (3-NT) in the hippocampal subregions of individuals with ADNC and their association with cognitive abilities.

Semi-Automated Interphase FISH (iFISH) Spot Scoring in CD138-Positive Cells: Validation Study for Genetic Abnormalities Detection in Multiple Myeloma.

We conducted a study to validate the automated scoring of Fluorescent in Situ Hybridization (FISH) in a routine cytogenetics laboratory using selected CD138-positive cells in samples from patients with multiple myeloma. A workstation was optimized based on the manufacturer's configurations. Six commercial probes (CDKN2C/CKS1B, RB1/DLEU1/LAMP1, TP53/CEN17, FGFR3::IGH, CCND1::IGH, and IGH::MAF) were examined to detect gains, losses, and rearrangements of genes across a total of 180 slides.

Role of the Mevalonate Pathway in Adrenocortical Tumorigenesis.

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway, which generates cholesterol and non-sterol compounds such as isoprenoid, which are involved in key steps of tumorigenesis such as cell growth and proliferation. Our aim was to evaluate the role of the mevalonate pathway in adrenocortical tumors (ACTs). Expression pattern of , , , , , , , , , , and genes involved in the mevalonate pathway and steroidogenesis, was quantified by real-time RT-PCR in 46 ACT [14 adenomas (ACA) and 11 carcinomas (ACC) from adults and 13 ACA and 8 ACC from pediatric patients].

Author Correction: A possible association between fructose consumption and pulmonary emphysema.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption.

The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups ( = 10). After 12 wk, the energy intake and body weight in the groups were similar.

A possible association between fructose consumption and pulmonary emphysema.

Chronic Obstructive Pulmonary Disease (COPD) is a syndrome that comprises several distinct and overlapping phenotypes. In addition to persistent airflow limitation and respiratory symptoms, COPD is also characterized by chronic systemic inflammation. Epidemiological studies have shown that dietary fibers, fruits and vegetables intake protects against the COPD development, while fructose-loading is associated with increased risk of asthma and chronic bronchitis.

Interesterified Fats Induce Deleterious Effects on Adipose Tissue and Liver in LDLr-KO Mice.

Interesterified fats are being widely used by the food industry in an attempt to replace trans fatty acids. The effect of interesterified fats containing palmitic or stearic acids on lipid metabolism and inflammatory signaling pathways in adipose and hepatic tissues was evaluated. Male LDLr-KO mice were fed a high-fat diet containing polyunsaturated (PUFA), palmitic (PALM), palmitic interesterified (PALM INTER), stearic (STEAR), or stearic interesterified (STEAR INTER) fats for 16 weeks.

Th17/Treg imbalance in COPD progression: A temporal analysis using a CS-induced model.

Background: The imbalance between pro- and anti-inflammatory immune responses plays a pivotal role in chronic obstructive pulmonary disease (COPD) development and progression. To clarify the pathophysiological mechanisms of this disease, we performed a temporal analysis of immune response-mediated inflammatory progression in a cigarette smoke (CS)-induced mouse model with a focus on the balance between Th17 and Treg responses.

Methods: C57BL/6 mice were exposed to CS for 1, 3 or 6 months to induce COPD, and the control groups were maintained under filtered air conditions for the same time intervals.

Fructose ingestion impairs expression of genes involved in skeletal muscle's adaptive response to aerobic exercise.

Background: The inverse relationship between exercise capacity and its variation over time and both cardiovascular and all-cause mortality suggests the existence of an etiological nexus between cardiometabolic diseases and the molecular regulators of exercise capacity. Coordinated adaptive responses elicited by physical training enhance exercise performance and metabolic efficiency and possibly mediate the health benefits of physical exercise. In contrast, impaired expression of genes involved in mitochondrial biogenesis or protein turnover in skeletal muscle-key biological processes involved in adaptation to physical training-leads to insulin resistance and obesity.

Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD.

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke).

Optimization of total RNA isolation from human urinary sediment.

Extracting RNA from human urinary sediment is notoriously challenging because of cell paucity and hostile environment and column-based commercial kits using silica technology are commonly used. Nonetheless, in our experience, this methodology yields low amounts of total RNA and has low rates of success. We replaced the column-based commercial kit by a protocol using guanidine isothiocyanate-phenol-chloroform buffer (Trizol reagent) followed by addition of glycogen as a carrier and precipitation with isopropanol plus sodium acetate.

Aerobic Exercise Reduces Asthma Phenotype by Modulation of the Leukotriene Pathway.

Introduction: Leukotrienes (LTs) play a central role in asthma. Low- to moderate-intensity aerobic exercise (AE) reduces asthmatic inflammation in clinical studies and in experimental models. This study investigated whether AE attenuates LT pathway activation in an ovalbumin (OVA) model of asthma.

Prevalence of thyroiditis and immunohistochemistry study searching for a morphologic consensus in morphology of autoimmune thyroiditis in a 4613 autopsies series.

We sought to verify the prevalence of lymphocytic thyroiditis (LT) and Hashimoto's thyroiditis (HT) in autopsy materials. Cases examined between 2003 and 2007 at the Department of Pathology of Faculty of Medicine of São Paulo University were studied. Immunohistochemical analyses were conducted in selected cases to characterize the type of infiltrating mononuclear cells; in addition, we evaluated the frequency of apoptosis by TUNEL assay technique and caspase-3 immunostaining.

Dietary phytosterol does not accumulate in the arterial wall and prevents atherosclerosis of LDLr-KO mice.

Scope: There have been conflicting reports on the usefulness of phytosterols (PS) in preventing atherosclerosis. We evaluated the effects of dietary PS supplementation in LDLr-KO male mice on the plasma and aorta sterol concentrations and on atherosclerotic lesion development.

Methods And Results: Mice were fed a high fat diet (40% of energy) supplemented with or without PS (2% w/w, n = 10).

Iodine increases and predicts incidence of thyroiditis in NOD mice: Histopathological and ultrastructural study.

Prolonged intake of large amounts of iodine has been reported to increase the incidence of hypothyroidism in humans, as well as in animals which are prone to spontaneously developing autoimmune thyroiditis. We sought to investigate the histopathological consequences of large amounts of dietary iodine on the thyroid gland and observe the occurrence of lymphocytic infiltration associated with the time of exposure to iodine. An experimental model using non-obese diabetic (NOD) mice was analyzed.

A method to immunolabel rodent spinal cord neurons and glia for molecular study in specific laser microdissected cells involved in neurodegenerative disorders.

Neuron-glia interaction is involved in physiological function of neurons, however, recent evidences have suggested glial cells as participants in neurotoxic and neurotrophic mechanisms of neurodegenerative/neuroregenerative processes. Laser microdissection offers a unique opportunity to study molecular regulation in specific immunolabeled cell types. However, an adequate protocol to allow morphological and molecular analysis of rodent spinal cord astrocyte, microglia and motoneurons remains a big challenge.

Possible role of a radiation-induced p53 mutation in a Nelson's syndrome patient with a fatal outcome.

Nelson's syndrome (NS) is characterized by the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for the treatment of Cushing's disease. Such corticotroph macroadenomas respond poorly to currently available therapeutic options which include surgery, radiotherapy and chemotherapy. P53 protein accumulation may be detected by immunohistochemistry in pituitary corticotroph adenomas and it has been suggested that it might be causally related to tumor development.

[Immunophenotyping and gene rearrangement analysis in lymphoid/lymphoproliferative disorders of the lungs].

Objective: To determine the usefulness, in routine practice, of using polymerase chain reaction to analyze B and T lymphocyte clonality in pulmonary tissue as a tool for the diagnosis of pulmonary lymphoproliferative disorders.

Methods: Immunohistochemistry and molecular gene rearrangement analysis were performed in order to assess 8 cases of lymphoid interstitial pneumonia (LIP) and 7 cases of pulmonary lymphoproliferative disorders.

Results: All 8 cases of LIP presented moderate to strong immunostaining for CD3, compared with only 2 cases of lymphoma and 1 case of pseudolymphoma (p = 0.

[Molecular mechanisms involved in adrenocortical tumorigenesis].

The adrenocortical tumorigenesis is a complex process, which involves multiple genetic changes. A better knowledge on the mechanisms involved in tumor development would enable an early identification of malignant disease and also lead to the development of new treatment strategies. Although in the recent years a large amount of data was produced, the exact mechanisms that lead to adrenocortical tumor development remains poorly understood.

[Gene silencing with RNA interference: a novel tool for the study of physiology and pathophysiology of adrenal cortex].

Loss-of-function approaches such as gene knock-out or gene silencing are extremely powerful strategies for assigning function to a gene and for mapping the interconnections of intracellular regulatory pathways. Post-transcriptional gene silencing can be obtained via activation of a double-stranded RNA (dsRNA) mediated mechanism termed RNA interference (RNAi). RNAi has revealed an extremely versatile tool in Biomedical research that can be used in both single silencing gene experiments and in large-scale Functional Genomics studies and has been used as a tool for gene therapy.

Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase.

Activation of vitamin D requires hepatic 25-hydroxylation and renal 1alpha-hydroxylation. Defects in renal P450c1alpha are well-described, but few patients with defective vitamin D 25-hydroxylation are reported. The cytochrome P450 enzymes CYP2D6 and CYP27 are potential 25-hydroxylases.