Experimental evidence of heparanase, Hsp70 and NF-κB gene expression on the response of anti-inflammatory drugs in TNBS-induced colonic inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Linfoma de Hodgkin: características anátomo-clínicas e análise de novo biomarcador (IMP3)

Pós-graduação em Patologia - FMB

O consumo de laticínios está associado à redução de triglicerídios e alterações na composição corporal de mulheres com sobrepeso e obesidade: um estudo de intervenção de 12 semanas

Pós-graduação em Saúde Coletiva - FMB

Can hydrogen peroxide and quercetin improve production of Eucalyptus grandis x Eucalyptus urophylla?

Vegetative propagation is considered the best choice for the rapid multiplication of plant species, however, rooting may still present difficulties. Substances, such as auxins, phenolic compounds and hydrogen peroxide, are recognized as able to improve this process. The aim of the present work was to determine if hydrogen peroxide in combination with quercetin or indole butyric acid, can modify some characteristics related to rooting and development in cuttings of Eucalyptus grandis x Eucalyptus urophylla. Cuttings were periodically evaluated at 30, 60 and 90 days according to the following criteria: height, diameter and survival percentage. After planting (90 days), a destructive evaluation was performed to determine rooting percentage, average size and number of roots. Polyamines content and polyamine oxidase activity, as biochemical markers of plant development, were determined. No statistically significant differences in height, diameter, survival and rooting percentage, root length and number of roots per cuttings were found. Treatments induced a decrease in putrescine levels and polyamine oxidase activity in roots. For absence of positive responses, the use of these substances as a treatment to improve cutting production is economically unviable.

Avaliação da prática de exercício físico (natação) de intensidade moderada no estresse oxidativo, hormônios sexuais e proliferação pancreática de ratas diabéticas prenhes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Oral Contraceptive Containing Chlormadinone Acetate and Ethinylestradiol Reduces Plasma Concentrations of Matrix Metalloproteinase-2 in Women with Polycystic Ovary Syndrome

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 mu g ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

Migrant labor and wear-out in manual sugarcane harvesting in Sao Paulo, Brazil

The scope of this paper is to describe the work of manual sugarcane harvesters, assessing the nutritional behavior and body composition between the beginning and the end of the harvest. A descriptive longitudinal study was made of harvesters in Piracicaba, Sao Paulo, Brazil, who answered a socio-demographic questionnaire and authorized measurement of Body Mass Index, Body Fat Percentage and Arm Muscle Circumference at three stages. Creatine kinase on the skeletal isoform, C-reactive protein and plasma urea were measured at the end of the harvest. Thirty male migrant harvesters with ages ranging from 18 to 44 from the Northeast (Ceara) were assessed over a nine-month period. The workers suffered significant body fat and weight loss in the first half of the harvest. Eighteen workers had abnormal levels of creatine kinase and four - out of 24 who had donated blood - had altered urea levels. Sugarcane harvesting work causes weight and body fat loss and gains in the lean body mass index, which suffers wear-out when working on consecutive harvests. It can also cause changes in biochemical markers of chronic systemic inflammation. Further studies will make it possible to comprehend the relationships between stress, wear-out, labor longevity and health in sugarcane harvesting.

Validation of a FFQ for estimating omega-3, omega-6 and trans fatty acid intake during pregnancy using mature breast milk and food recalls

BACKGROUND/OBJECTIVES: To assess the performance of a food frequency questionnaire (FFQ) for estimating omega-3, omega-6 and trans fatty acid intake during pregnancy. Moreover, we determined whether the fatty acid composition of mature breast milk represents a valuable biomarker for fatty acid intake during pregnancy. SUBJECTS/METHODS: A prospective study in 41 pregnant women, aged 18-35 years, was conducted. Food intake during pregnancy was evaluated by three 24-h recalls (24 hR), and 2 FFQ. The fatty acid composition of mature breast milk was determined by gas chromatography. The method of triads and joint classification between quartiles of intake were applied. RESULTS: The FFQ was accurate for estimating docosahexanoic (DHA), linoleic and total omega-6 fatty acids according to validity coefficients. Higher agreements (>70%) into the same or adjacent quartiles between the dietary methods were found for alpha-linolenic, total omega-3, linoleic and trans fatty acid intake. High validity coefficients for eicosapentanoic (EPA) and DHA acids of human milk were found (0.61 and 0.73, respectively), and the method was adequate for categorizing the intake of alpha-linolenic, total omega-3 and trans fatty acids compared with FFQ estimates, and for arachidonic acid and trans fatty acids compared with food recall estimates, during pregnancy. CONCLUSIONS: The FFQ was an accurate tool for categorizing alpha-linolenic, total omega-3 and trans fatty acid intake. According to the validity coefficients observed, the FFQ accurately estimated DHA, linoleic and total omega-6 fatty acids and the composition of mature breast milk was shown to be a suitable biomarker for EPA and DHA fatty acid intake during pregnancy.

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

Migrant labor and wear-out in manual sugarcane harvesting in São Paulo, Brazil

The scope of this paper is to describe the work of manual sugarcane harvesters, assessing the nutritional behavior and body composition between the beginning and the end of the harvest. A descriptive longitudinal study was made of harvesters in Piracicaba, São Paulo, Brazil, who answered a socio-demographic questionnaire and authorized measurement of Body Mass Index, Body Fat Percentage and Arm Muscle Circumference at three stages. Creatine kinase on the skeletal isoform, C-reactive protein and plasma urea were measured at the end of the harvest. Thirty male migrant harvesters with ages ranging from 18 to 44 from the Northeast (Ceará) were assessed over a nine-month period. The workers suffered significant body fat and weight loss in the first half of the harvest. Eighteen workers had abnormal levels of creatine kinase and four - out of 24 who had donated blood - had altered urea levels. Sugarcane harvesting work causes weight and body fat loss and gains in the lean body mass index, which suffers wear-out when working on consecutive harvests. It can also cause changes in biochemical markers of chronic systemic inflammation. Further studies will make it possible to comprehend the relationships between stress, wear-out, labor longevity and health in sugarcane harvesting.

Sindrome di Down e fattori di rischio nel declino neurocognitivo

Down syndrome (DS) or Trisomy 21, occurring in 1/700 and 1/1000 livebirths, is the most common genetic disorder, characterized by a third copy of the human chromosome 21 (Hsa21). DS is associated with various defects, including congenital heart diseases, craniofacial abnormalities, immune system dysfunction, mental retardation (MR), learning and memory deficiency. The phenotypic features in DS are a direct consequence of overexpression of genes located within the triplicated region on Hsa21. In addition to developmental brain abnormalities and disabilities, people with DS by the age of 30-40 have a greatly increased risk of early-onset of Alzheimer’s disease (AD) and an apparent tendency toward premature aging. Many of the immunological anomalies in DS can be enclosed in the spectrum of multiple signs of early senescence. People with DS have an increased vulnerability to oxidative damage and many factors, including amyloid beta protein (Abeta), genotype ApoE4, oxidative stress, mutations in mitochondrial DNA (mtDNA), impairment of antioxidant enzymes, accelerated neuronal cell apoptosis, are related to neuronal degeneration and early aging in DS. SUBJECTS and METHODS: Since 2007 a population of 50 adolescents and adults with DS, 26 males and 24 females (sex-ratio: M/F = 1.08), has been evaluated for the presence of neurological features, biomarkers and genetic factors correlated with neuronal degeneration and premature aging. The control group was determined by the mother and the siblings of the patients. A neuropsychiatric evaluation was obtained from all patients. The levels of thyroid antibodies (antiTg and antiTPO) and of some biochemical markers of oxidative stress, including homocysteine (tHcy), uric acid, cobalamin, folate were measured. All patients, the mother and the siblings were genotyped for ApoE gene. RESULTS: 40% of patients, with a mild prevalence of females aged between 19 and 30 years, showed increased levels of antiTg and antiTPO. The levels of tHcy were normal in 52% patients and mildly increased in 40%; hyperomocysteinemia was associated with normal levels of thyroid antibodies in 75% of patients (p<0.005). The levels of uric acid were elevated in 26%. Our study showed a prevalence of severe MR in patients aged between 1-18 years and over 30 years. Only 3 patients, 2 females and one male, over 30 years of age, showed dementia. According to the literature, the rate of Down left-handers was high (25%) compared to the rest of population and the laterality was associated with increased levels of thyroid antibodies (70%). 21.5% of patients were ApoE4 positive (ApoE4+) with a mean/severe MR. CONCLUSIONS: Until now no biochemical evidence of oxidative damage and no deficiency or alteration of antioxidant function in our patients with DS were found. mtDNA sequencing could show some mutations age-related and associated with oxidative damage and neurocognitive decline in the early aging of DS. The final aim is found predictive markers of early-onset dementia and a target strategy for the prevention and the treatment of diseases caused by oxidative stress. REFERENCES: 1) Rachidi M, Lopes C: “Mental retardation and associated neurological dysfunctions in Down syndrome: a consequence of dysregulation in critical chromosome 21 genes and associated molecular pathways.” - Eur J Paediatr Neurol. May;12(3):168-82 (2008). 2) Lott IT, Head E: “Down syndrome and Alzheimer's disease: a link between development and aging.” - Ment Retard Dev Disabil Res Rev, 7(3):172-8 (2001). 3) Lee HC, Wei YH: “Oxidative Stress, Mitochondrial DNA Mutation, and Apoptosis in Aging.” - Exp Biol Med (Maywood), May;232(5):592-606 (2007).

Valutazione dei disturbi cognitivi nei pazienti sottoposti a Rivascolarizzazione Carotidea (Endoarterectomia vs Stenting) mediante dosaggio di marker di danno neuronale, Mini Mental State Examination e Risonanza Magnetica

Scopo del nostro studio è quello di valutare i disturbi cognitivi in relazione al tasso di microembolia cerebrale in due gruppi di pazienti trattati per lesione carotidea asintomatica con endoarterectomia (CEA) o stenting (CAS). Comparando le due metodiche mediante l’utilizzo di risonanza magnetica in diffusione (DW-MRI), neuromarkers (NSE e S100β) e test neuropsicometrici. MATERIALE E METODI: 60 pazienti sono stati sottoposti a rivascolarizzazione carotidea (CEA n=32 e CAS n=28). Sono stati tutti valutati con DW-MRI e Mini-Mental State Examination (MMSE) test nel preoperatorio, a 24 ore, a 6 ed a 12 mesi dall’intervento. In tutti sono stati dosati i livelli sierici di NSE e S100β mediante 5 prelievi seriati nel tempo, quello basale nel preoperatorio, l’ultimo a 24 ore. L’ananlisi statistica è stata effettuata con test t di Student per confronti multipli per valori continui e con test χ2 quadro e Fisher per le variabili categoriche. Significatività P <0,05. RISULTATI: Non vi è stato alcun decesso. Un paziente del gruppo CAS ha presentato un ictus ischemico. In 6 pazienti CAS ed in 1 paziente CEA si sono osservate nuove lesioni subcliniche alla RMN-DWI post-operatoria (21,4% vs 3% p=0,03). Nel gruppo CAS le nuove lesioni presenti alla RMN sono risultate significativamente associate ad un declino del punteggio del MMSE (p=0,001). L’analisi dei livelli di NSE e S100β ha mostrato un significativo aumento a 24 ore nei pazienti CAS (P = .02). A 12 mesi i pazienti che avevano presentato nuove lesioni ischemiche nel post-operatorio hanno mostrato minor punteggio al MMSE, non statisticamente significativo. CONCLUSIONI: I neuromarkers in combinazione con MMSE e RMN-DWI possono essere utilizzati nella valutazione del declino cognitivo correlato a lesioni silenti nell’immediato postoperatorio di rivascolarizzazione carotidea. Quest’ultime dovrebbero essere valutate quindi non solo rispetto al tasso di mortalità e ictus, ma anche rispetto al tasso di microembolia.

The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.

Prevalence of vitamin B12 depletion and deficiency in Liechtenstein

OBJECTIVE: Data about vitamin B12 (B12) deficiency in the general population are scarce. The present study was performed to determine the prevalence of B12 deficiency in the general population of the Principality of Liechtenstein, as well as to identify sub-populations potentially at high risk. DESIGN: Retrospective study. SETTING: Ambulatory setting, population of the Principality of Liechtenstein. SUBJECTS: Seven thousand four hundred and twenty-four patients seeking medical attention whose serum samples were referred for routine work-up in an ambulatory setting were consecutively enrolled. Serum total B12 was determined in all patients in this cohort. In addition, for a subgroup of 1328 patients, serum holotranscobalamin was also measured. Prevalence of B12 deficiency was calculated. Further, multivariate logistical regression models were applied to identify covariates independently associated with B12 deficiency and depletion. RESULTS: Nearly 8 % of the general population was suffering from either B12 depletion or deficiency. The ratio between B12 depletion and deficiency was 2:1 for all age ranges. Pathological changes were detected predominantly in older people. Female gender was a significant predictor of B12 depletion. In the cohort, nearly 40 % exhibited either depletion or deficiency of B12. CONCLUSIONS: B12 depletion and deficiency are common in Liechtenstein, a Central European country. The measurement of biochemical markers represents a cost-efficient and valid assessment of the B12 state. When a deficiency of B12 is diagnosed at an early stage, many cases can be treated or prevented, with beneficial effects on individual outcomes and subsequent potential reductions in health-care costs.

Anti-Müllerian hormone levels in girls and adolescents with Turner syndrome are related to karyotype, pubertal development and growth hormone treatment

In girls and adolescents with Turner syndrome (TS), is there a correlation between serum AMH levels and karyotype, spontaneous puberty and other biochemical markers of ovarian function, or growth hormone (GH) therapy? SUMMARY ANSWER: Serum anti-Müllerian hormone (AMH) correlates with karyotype, pubertal development, LH, FSH and are measurable in a higher percentage of TS patients under GH therapy. WHAT IS KNOWN ALREADY: Most girls with TS suffer from incomplete sexual development, premature ovarian failure and infertility due to abnormal ovarian folliculogenesis. Serum AMH levels reflect the ovarian reserve in females, even in childhood. STUDY DESIGN, SIZE, DURATION: Cross-sectional study investigating 270 karyotype proven TS patients aged 0-20 years between 2009 and 2010. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Studies were conducted at three University Children's hospitals in Europe. Main outcome measures were clinical data concerning pubertal development as well as laboratory data including karyotype, serum AMH, LH, FSH, estradiol (E2), inhibin B and IGF. RESULTS AND THE ROLE OF CHANCE: Serum AMH was detectable in 21.9% of all TS girls and correlated strongly with karyotypes. A measurable serum AMH was found in 77% of TS girls with karyotype 45,X/46,XX, in 25% with 'other' karyotypes and in only 10% of 45,X TS girls. A strong relationship was also observed for measurable serum AMH and signs of spontaneous puberty such as breast development [adjusted odds ratio (OR) 19.3; 95% CI 2.1-175.6; P = 0.009] and menarche (crude OR 47.6; 95% CI 4.8-472.9; P = 0.001). Serum AMH correlated negatively with FSH and LH, but did not correlate with E2 and inhibin B. GH therapy increased the odds of having measurable AMH in TS (adjusted OR 4.1; 95% CI 1.9-8.8; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The cross-sectional design of the study does not allow longitudinal interpretation of the data; for that further studies are needed. High percentage of non-measurable AMH levels in the cohort of TS require categorized analysis. WIDER IMPLICATIONS OF THE FINDINGS: Serum AMH levels are a useful marker of the follicle pool and thus ovarian function in pediatric patients with TS. These findings are in line with the published literature. The finding that GH therapy may affect AMH levels is novel, but must be confirmed by future longitudinal studies.