Role Of Astrocytes In Thiamine Deficiency.

Thiamine deficiency (TD) is the underlying cause of Wernicke's encephalopathy (WE), an acute neurological disorder characterized by structural damage to key periventricular structures in the brain. Increasing evidence suggests these focal histological lesions may be representative of a gliopathy in which astrocyte-related changes are a major feature of the disorder. These changes include a loss of the glutamate transporters GLT-1 and GLAST concomitant with elevated interstitial glutamate levels, lowered brain pH associated with increased lactate production, decreased levels of GFAP, reduction in the levels of glutamine synthetase, swelling, alterations in levels of aquaporin-4, and disruption of the blood-brain barrier. This review focusses on how these manifestations contribute to the pathophysiology of TD and possibly WE.

Growth And Body Composition In Brazilian Female Rhythmic Gymnastics Athletes.

The aim was to analyse the physical growth and body composition of rhythmic gymnastics athletes relative to their level of somatic maturation. This was a cross-sectional study of 136 athletes on 23 teams from Brazil. Mass, standing height and sitting height were measured. Fat-free and fat masses, body fat percentages and ages of the predicted peak height velocity (PHV) were calculated. The z scores for mass were negative during all ages according to both WHO and Brazilian references, and that for standing height were also negative for all ages according to WHO reference but only until 12 years old according to Brazilian reference. The mean age of the predicted PHV was 12.1 years. The mean mass, standing and sitting heights, body fat percentage, fat-free mass and fat mass increased significantly until 4 to 5 years after the age of the PHV. Menarche was reached in only 26% of these athletes and mean age was 13.2 years. The mass was below the national reference standards, and the standing height was below only for the international reference, but they also had late recovery of mass and standing height during puberty. In conclusion, these athletes had a potential to gain mass and standing height several years after PHV, indicating late maturation.

The Inadequacy Of The Y-axis Of Growth (sngn) For The Vertical Pattern Assessment In Patients With Sagittal Discrepancies.

The aim of this cephalometric study was to evaluate the influence of the sagittal skeletal pattern on the 'Y-axis of growth' measurement in patients with different malocclusions. Lateral head films from 59 patients (mean age 16y 7m, ranging from 11 to 25 years) were selected after a subjective analysis of 1630 cases. Sample was grouped as follows: Group 1 - class I facial pattern; group 2 - class II facial pattern; and Group 3 - class III facial pattern. Two angular measurements, SNGoGn and SNGn, were taken in order to determine skeletal vertical facial pattern. A logistic regression with errors distributed according to a binomial distribution was used to test the influence of the sagittal relationship (Class I, II, III facial patterns) on vertical diagnostic measurement congruence (SNGoGn and SNGn). RESULTS show that the probability of congruence between the patterns SNGn and SNGoGn was relatively high (70%) for group 1, but for groups II (46%) and III (37%) this congruence was relatively low. The use of SNGn appears to be inappropriate to determine the vertical facial skeletal pattern of patients, due to Gn point shifting throughout sagittal discrepancies. Clinical Significance: Facial pattern determined by SNGn must be considered carefully, especially when severe sagittal discrepancies are present.

The Effect Of Soy Dietary Supplement And Low Dose Of Hormone Therapy On Main Cardiovascular Health Biomarkers: A Randomized Controlled Trial.

To assess the effects of a soy dietary supplement on the main biomarkers of cardiovascular health in postmenopausal women compared with the effects of low-dose hormone therapy (HT) and placebo. Double-blind, randomized and controlled intention-to-treat trial. Sixty healthy postmenopausal women, aged 40-60 years, 4.1 years mean time since menopause were recruited and randomly assigned to 3 groups: a soy dietary supplement group (isoflavone 90mg), a low-dose HT group (estradiol 1 mg plus noretisterone 0.5 mg) and a placebo group. Lipid profile, glucose level, body mass index, blood pressure and abdominal/hip ratio were evaluated in all the participants at baseline and after 16 weeks. Statistical analyses were performed using the χ2 test, Fisher's exact test, Kruskal-Wallis non-parametric test, analysis of variance (ANOVA), paired Student's t-test and Wilcoxon test. After a 16-week intervention period, total cholesterol decreased 11.3% and LDL-cholesterol decreased 18.6% in the HT group, but both did not change in the soy dietary supplement and placebo groups. Values for triglycerides, HDL-cholesterol, glucose level, body mass index, blood pressure and abdominal/hip ratio did not change over time in any of the three groups. The use of dietary soy supplement did not show any significant favorable effect on cardiovascular health biomarkers compared with HT. The trial is registered at the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC), number RBR-76mm75.

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

Pyrimidine-5'-nucleotidase Campinas, A New Mutation (p.r56g) In The Nt5c3 Gene Associated With Pyrimidine-5'-nucleotidase Type I Deficiency And Influence Of Gilbert's Syndrome On Clinical Expression.

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.

Interplay Between Cell Growth And Cell Cycle In Plants.

The growth of organs and whole plants depends on both cell growth and cell-cycle progression, but the interaction between both processes is poorly understood. In plants, the balance between growth and cell-cycle progression requires coordinated regulation of four different processes: macromolecular synthesis (cytoplasmic growth), turgor-driven cell-wall extension, mitotic cycle, and endocycle. Potential feedbacks between these processes include a cell-size checkpoint operating before DNA synthesis and a link between DNA contents and maximum cell size. In addition, key intercellular signals and growth regulatory genes appear to target at the same time cell-cycle and cell-growth functions. For example, auxin, gibberellin, and brassinosteroid all have parallel links to cell-cycle progression (through S-phase Cyclin D-CDK and the anaphase-promoting complex) and cell-wall functions (through cell-wall extensibility or microtubule dynamics). Another intercellular signal mediated by microtubule dynamics is the mechanical stress caused by growth of interconnected cells. Superimposed on developmental controls, sugar signalling through the TOR pathway has recently emerged as a central control point linking cytoplasmic growth, cell-cycle and cell-wall functions. Recent progress in quantitative imaging and computational modelling will facilitate analysis of the multiple interconnections between plant cell growth and cell cycle and ultimately will be required for the predictive manipulation of plant growth.

Vascular Endothelial Growth Factor Increases During Blood-brain Barrier-enhanced Permeability Caused By Phoneutria Nigriventer Spider Venom.

Phoneutria nigriventer spider accidental envenomation provokes neurotoxic manifestations, which when critical, results in epileptic-like episodes. In rats, P. nigriventer venom (PNV) causes blood-brain barrier breakdown (BBBb). The PNV-induced excitotoxicity results from disturbances on Na(+), K(+) and Ca(2+) channels and glutamate handling. The vascular endothelial growth factor (VEGF), beyond its angiogenic effect, also, interferes on synaptic physiology by affecting the same ion channels and protects neurons from excitotoxicity. However, it is unknown whether VEGF expression is altered following PNV envenomation. We found that adult and neonates rats injected with PNV showed immediate neurotoxic manifestations which paralleled with endothelial occludin, β-catenin, and laminin downregulation indicative of BBBb. In neonate rats, VEGF, VEGF mRNA, and Flt-1 receptors, glutamate decarboxylase, and calbindin-D28k increased in Purkinje neurons, while, in adult rats, the BBBb paralleled with VEGF mRNA, Flk-1, and calbindin-D28k increases and Flt-1 decreases. Statistically, the variable age had a role in such differences, which might be due to age-related unequal maturation of blood-brain barrier (BBB) and thus differential cross-signaling among components of the glial neurovascular unit. The concurrent increases in the VEGF/Flt-1/Flk-1 system in the cerebellar neuron cells and the BBBb following PNV exposure might imply a cytokine modulation of neuronal excitability consequent to homeostatic perturbations induced by ion channels-acting PNV neuropeptides. Whether such modulation represents neuroprotection needs further investigation.

Micronutrient And Physiologic Parameters Before And 6 Months After Rygb.

Bariatric surgery is considered an effective method for sustained weight loss, but may cause various nutritional complications. The aim of this study was to evaluate the nutritional status of minerals and vitamins, food consumption, and to monitor physiologic parameters in patients with obesity before and 6 months after Roux-en-Y gastric bypass surgery (RYGB). Thirty-six patients who had undergone RYGB were prospectively evaluated before and 6 months after surgery. At each phase their weight, height, body mass index (BMI), Electro Sensor Complex (ES Complex) data, food consumption, and total protein serum levels, albumin, prealbumin, parathyroid hormone (PTH), zinc (Zn), B12 vitamin (VitB12), iron (Fe), ferritin, copper (Cu), ionic calcium (CaI), magnesium (Mg), and folic acid were assessed. The mean weight loss from baseline to 6 months after surgery was 35.34±4.82%. Markers of autonomic nervous system balance (P<.01), stiffness index (P<.01), standard deviation of normal-to-normal R-R intervals (SDNN) (P<.01), and insulin resistance (P<.001) were also improved. With regard to the micronutrients measured, 34 patients demonstrated some kind of deficiency. There was a high percentage of Zn deficiency in both pre- (55.55%) and postoperative (61.11%) patients, and 33.33% of the patients were deficient in prealbumin postoperatively. The protein intake after 6 months of surgery was below the recommended intake (<70 g/d) for 88.88% of the patients. Laboratory analyses demonstrated an average decrease in total protein (P<.05), prealbumin (P = .002), and PTH (P = .008) between pre- and postsurgery, and a decrease in the percentage of deficiencies for Mg (P<.05), CaI (P<.05), and Fe (P = .021). Despite improvements in the autonomic nervous system balance, stiffness index markers and insulin resistance, we found a high prevalence of hypozincemia at 6 months post-RYGB. Furthermore, protein supplements were needed to maintain an adequate protein intake up to 6 months postsurgery.

Evaluation Of Red Cell And Reticulocyte Parameters As Indicative Of Iron Deficiency In Patients With Anemia Of Chronic Disease.

The purpose of this study was to evaluate the effectiveness of mature red cell and reticulocyte parameters under three conditions: iron deficiency anemia, anemia of chronic disease, and anemia of chronic disease associated with absolute iron deficiency. Peripheral blood cells from 117 adult patients with anemia were classified according to iron status, and inflammatory activity, and the results of a hemoglobinopathy investigation as: iron deficiency anemia (n=42), anemia of chronic disease (n=28), anemia of chronic disease associated with iron deficiency anemia (n=22), and heterozygous β thalassemia (n=25). The percentage of microcytic red cells, hypochromic red cells, and levels of hemoglobin content in both reticulocytes and mature red cells were determined. Receiver operating characteristic analysis was used to evaluate the accuracy of the parameters in differentiating between the different types of anemia. There was no significant difference between the iron deficient group and anemia of chronic disease associated with absolute iron deficiency in respect to any parameter. The percentage of hypochromic red cells was the best parameter to discriminate anemia of chronic disease with and without absolute iron deficiency (area under curve=0.785; 95% confidence interval: 0.661-0.909, with sensitivity of 72.7%, and specificity of 70.4%; cut-off value 1.8%). The formula microcytic red cells minus hypochromic red cells was very accurate in differentiating iron deficiency anemia and heterozygous β thalassemia (area under curve=0.977; 95% confidence interval: 0.950-1.005; with sensitivity of 96.2%, and specificity of 92.7%; cut-off value 13.8). The indices related to red cells and reticulocytes have a moderate performance in identifying absolute iron deficiency in patients with anemia of chronic disease.

Frequency Of The Allelic Variant C.1150t > C In Exon 10 Of The Fibroblast Growth Factor Receptor 3 (fgfr3) Gene Is Not Increased In Patients With Pathogenic Mutations And Related Chondrodysplasia Phenotypes.

Mutations in the FGFR3 gene cause the phenotypic spectrum of FGFR3 chondrodysplasias ranging from lethal forms to the milder phenotype seen in hypochondroplasia (Hch). The p.N540K mutation in the FGFR3 gene occurs in ∼70% of individuals with Hch, and nearly 30% of individuals with the Hch phenotype have no mutations in the FGFR3, which suggests genetic heterogeneity. The identification of a severe case of Hch associated with the typical mutation c.1620C > A and the occurrence of a c.1150T > C change that resulted in a p.F384L in exon 10, together with the suspicion that this second change could be a modulator of the phenotype, prompted us to investigate this hypothesis in a cohort of patients. An analysis of 48 patients with FGFR3 chondrodysplasia phenotypes and 330 healthy (control) individuals revealed no significant difference in the frequency of the C allele at the c.1150 position (p = 0.34). One patient carrying the combination `pathogenic mutation plus the allelic variant c.1150T > C' had a typical achondroplasia (Ach) phenotype. In addition, three other patients with atypical phenotypes showed no association with the allelic variant. Together, these results do not support the hypothesis of a modulatory role for the c.1150T > C change in the FGFR3 gene.

Long-term Follow-up Of Patients With 46,xy Partial Gonadal Dysgenesis Reared As Males.

Background/Aims. Studies on 46,XY partial gonadal dysgenesis (PGD) have focused on molecular, gonadal, genital, and hormone features; little is known about follow-up. Our aim was to analyze long-term outcomes of PGD. Methods. Retrospective longitudinal study conducted at a reference service in Brazil. Ten patients were first evaluated in the 1990s and followed up until the 2010s; follow-up ranged from 13.5 to 19.7 years. All were reared as males and had at least one scrotal testis; two bore NR5A1 mutations. Main outcomes were: associated conditions, pubertal development, and growth. Results. All patients had normal motor development but three presented cognitive impairment; five had various associated conditions. At the end of the prepubertal period, FSH was high or high-normal in 3/6 patients; LH was normal in all. At the last evaluation, FSH was high or high-normal in 8/10; LH was high or high-normal in 5/10; testosterone was decreased in one. Final height in nine cases ranged from -1.57 to 0.80 SDS. All had spontaneous puberty; only one needed androgen therapy. Conclusions. There is good prognosis for growth and spontaneous pubertal development but not for fertility. Though additional studies are required, screening for learning disabilities is advisable.

Correlation Between Vascular Endothelial Growth Factor Expression And Presence Of Lymph Node Metastasis In Advanced Squamous Cell Carcinoma Of The Larynx.

Squamous cell carcinoma is the most common neoplasm of the larynx, and its evolution depends on tumor staging. Vascular endothelial growth factor is a marker of angiogenesis, and its expression may be related to increased tumor aggressiveness, as evidenced by the presence of cervical lymphatic metastases. To evaluate the expression of the vascular endothelial growth factor marker in non-glottic advanced squamous cell carcinoma of the larynx (T3/T4) and correlate it with the presence of cervical lymph node metastases. Retrospective clinical study and immunohistochemical analysis of vascular endothelial growth factor through the German scale of immunoreactivity in products of non-glottic squamous cell carcinomas. This study analyzed 15 cases of advanced non-glottic laryngeal tumors (T3/T4), four of which exhibited cervical lymphatic metastases. There was no correlation between vascular endothelial growth factor expression and the presence of cervical metastases. Although vascular endothelial growth factor was expressed in a few cases, there was no correlation with the spread of cervical lymph metastases.

Vaginal Epithelium And Microflora Characteristics In Women With Premature Ovarian Failure Under Hormone Therapy Compared To Healthy Women.

To evaluate some microbiological aspects of the vaginal flora and the vaginal trophism of women with premature ovarian failure (POF) in use of oral hormone therapy. A cross-sectional study with 36 women with POF under the age of 40 years using oral hormonal therapy. They were age matched with 36 women with normal gonadal function (control group). The characteristics of the vaginal epithelium were assessed through the hormonal vaginal cytology, vaginal pH measurement and vaginal health index to identify vaginal disturbances. Vaginal microflora was evaluated by the amine test, bacterioscopy (Nugent score) and culture for fungi to identify vaginal abnormal microflora and fungi infections. Despite the fact that there were no statistical significant differences related to the cytological aspects and pH measurements, it was found that the vaginal health index was highly superior in the control group than in the POF group (23.4 ± 1.8 vs 20.8 ± 3.5), p < 0.0001 despite both groups had trophic scores. There were no statistical significance differences regarding to vaginal microflora types and fungi infection. Oral hormone therapy for young women with POF seems to be good enough to reestablish the epithelium cells, vaginal pH and microflora.

Semi-determinate Growth Habit Adjusts The Vegetative-to-reproductive Balance And Increases Productivity And Water-use Efficiency In Tomato (solanum Lycopersicum).

Tomato (Solanum lycopersicum) shows three growth habits: determinate, indeterminate and semi-determinate. These are controlled mainly by allelic variation in the SELF-PRUNING (SP) gene family, which also includes the florigen gene SINGLE FLOWER TRUSS (SFT). Determinate cultivars have synchronized flower and fruit production, which allows mechanical harvesting in the tomato processing industry, whereas indeterminate ones have more vegetative growth with continuous flower and fruit formation, being thus preferred for fresh market tomato production. The semi-determinate growth habit is poorly understood, although there are indications that it combines advantages of determinate and indeterminate growth. Here, we used near-isogenic lines (NILs) in the cultivar Micro-Tom (MT) with different growth habit to characterize semi-determinate growth and to determine its impact on developmental and productivity traits. We show that semi-determinate genotypes are equivalent to determinate ones with extended vegetative growth, which in turn impacts shoot height, number of leaves and either stem diameter or internode length. Semi-determinate plants also tend to increase the highly relevant agronomic parameter Brix×ripe yield (BRY). Water-use efficiency (WUE), evaluated either directly as dry mass produced per amount of water transpired or indirectly through C isotope discrimination, was higher in semi-determinate genotypes. We also provide evidence that the increases in BRY in semi-determinate genotypes are a consequence of an improved balance between vegetative and reproductive growth, a mechanism analogous to the conversion of the overly vegetative tall cereal varieties into well-balanced semi-dwarf ones used in the Green Revolution.