Recent studies indicate disruptions to the circadian system in brain injury and neurodegeneration. The results, however, are often not consistent and limited by measurement of only one circadian ...marker and by infrequent sampling rates. In this study, we examined diurnal rhythmicity in different stages of Huntington (HD) disease and in patients with acute moderate ischemic stroke (AIS) outside the retinohypothalamic pathway by evaluating serum concentrations of melatonin and cortisol at twelve timepoints. All study participants were subjected to the same study protocol of 12-hour light/dark cycle and controlled room conditions. Using cosinor analysis of data and comparing the results with the controls we found melatonin phase delay with lowered amplitude and mesor in stage III HD patients. These changes coexisted with phase advanced rhythm and elevated values of mesor and amplitude for cortisol. Early and mid-stages of HD showed only a phase advance in cortisol secretion. In AIS the circadian rhythm of serum melatonin was sustained without any phase shift and exhibited more flattened profile (lowered mesor and amplitude values), while advanced rhythm with higher mesor for cortisol was present. In conclusion, 1) abnormal pattern of melatonin release in the late stages of HD and in moderate AIS occurs in conjunction with phase-advanced rhythm of cortisol; 2) changes observed in late stages of HD are similar to those that occur with ageing; 3) brain regions other than the presumptive retinopineal neural pathway may play an important role in the pineal production of melatonin in humans; 4) lesion in extrahypothalamic region is related to the strong adrenal stimulation in response to AIS.
Spirulina maxima consumption is known to be associated with enhanced cardiovascular and metabolic health. Human studies on this topic have recently been described in a few papers; however, potential ...protective cardiovascular properties of Spirulina in obese patients receiving standard pharmacological antihypertensive treatment remain to be elucidated. Putative beneficial cardiovascular effects of Spirulina supplementation in well treated, obesity-related hypertension were studied in a double-blind placebo-controlled trial.
Total 50 obese subjects with treated hypertension, each randomized to receive 2 g of Spirulina or a placebo daily, for three months. At baseline and after treatment anthropometric parameters, plasma lipid levels, inflammation, and oxidative stress biomarkers along with insulin sensitivity estimated by euglycemic clamp were assessed.
After three months of Spirulina supplementation significant decrease in body mass (p < 0.001), body mass index (BMI; p < 0.001) and waist circumference (WC; p = 0.002) were observed in Spirulina group. Spirulina had also significant, lowering effect on low-density lipoprotein cholesterol (LDL-C; p < 0.001) and interleukin-6 (IL-6) concentration (p = 0.002) in supplemented patients compared to placebo group. Spirulina supplementation considerably improved total antioxidant status (TAS; p = 0.001) and insulin sensitivity ratio (M; p < 0.001) in Spirulina group compared to placebo-treated individuals.
The favorable influence of Spirulina supplementation on insulin sensitivity, plasma lipid levels along with inflammation and oxidative stress biomarkers reported in this study creates the promise for new therapeutic approaches in obese patients with well-treated hypertension.
To meet energy demands for lactogenesis and to sustain homeostatic conditions post-partum, the organism of breastfeeding mother undergoes combined endocrine and metabolic regulation. The main ...objective of this study was to determine basal serum concentrations of hormones involved in the maintenance and defense of energy balance in breastfeeding (BF) and formula feeding (FF) mothers. Twenty healthy exclusively breastfeeding mothers at 3
month of lactation (EBF3), 17 healthy partially breastfeeding at 6
month of lactation (PB6) and 17 healthy FF mothers participated in this study. Fasting serum prolactin (PRL), acylated ghrelin (aGhr), total ghrelin (tGhr), leptin, adiponectin, insulin, and cortisol were determined for all study participants and correlations between studied parameters were calculated for BF women. We found significantly lower basal insulin (p = 0.0048) and cortisol (p = 0.0002) and significantly elevated basal prolactin (p = 0.0020) and leptin (p = 0.0416) in BF when compared with FF women. The differences were not associated with the duration of lactation (3 vs. 6 months), except for PRL, which was highest in EBF3. Levels of Ghr and adiponectin did not differ between study groups. In the BF group, the negative correlations were found between: aGhr and insulin, aGhr and adiponectin, leptin and cortisol, leptin and adiponectin, insulin and adiponectin, cortisol and adiponectin. Positive associations were noted between: insulin and leptin, leptin and aGhr, PRL and leptin, PRL and aGhr. Leptin and insulin correlated positively, whereas adiponectin negatively with BMI. These data may suggest that EBF3 and PB6 as compared with FF mothers, exhibit hormonal regulation which tends to be more advantageous for their metabolic profile and is not related to the duration of breastfeeding within the first 6 months of lactation.
We examined an association between ghrelin, including its major isoforms, interleukin-6 (IL-6), body mass index (BMI), and mean arterial pressure (MAP) in male overweight patients with essential ...hypertension. Twenty hypertensive male patients with newly diagnosed essential hypertension (EH) before starting drug treatment and 22 age-matched healthy controls were enrolled in the study. Fasting total plasma ghrelin (TGhr), acyl ghrelin (AGhr), des-acyl ghrelin (DGhr) and IL-6 were determined and correlations between studied parameters were calculated. We found significantly lower total plasma ghrelin and higher plasma IL-6 in hypertensives when compared with the control. In patients with hypertension the negative correlations were found: between TGhr and BMI, DGhr and BMI, TGhr and MAP, and between DGhr and MAP. IL-6 positively correlated with BMI and MAP in hypertensive subjects. No correlations between all forms of ghrelin and IL-6 were noted. The changes in plasma ghrelin and IL-6 contribute independently to the elevated blood pressure in essential hypertension. Negative correlation of DGhr and MAP may suggest its hemodynamic involvement in regulation of blood pressure.
It has been proposed that regular cold swimming is associated with health benefits. However, the effect of cold adaptation on particular cardiovascular risk factors, within a single swimming season, ...remains unknown. Our aim was to evaluate the impact of cold water swimming on the seasonal changes in lipid profile and on apolipoprotein and homocysteine concentration in 34 cold water swimmers (CWS) aged 48 - 68 years. Blood samples were collected at the beginning (October), the middle (January), and the end (April) of the swimming season. Body mass (BM), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), ApoB/ApoA-I ratio, and homocysteine concentrations were evaluated. In October, female CWS showed lower BM (P = 0.01), TG concentrations (P = 0.03), and ApoB/ApoA-I ratios (P = 0.008), and higher HDL (P = 0.01) than in men. Similar trends in BM (P = 0.002), HDL (P = 0.0006), and ApoB/ApoA-I ratio (P = 0.01) were seen in January, and for BM (P = 0.002), TG (P = 0.005), HDL (P = 0.003), and ApoB/ApoA-I (P = 0.01) in April. A decrease in TG concentration between January and April (P = 0.05), lower homocysteine concentration between October and January (P = 0.01), and between October and April (P = 0.001) were documented in CWS. A strong drop in homocysteine concentration was observed in female versus male CWS (P = 0.001 versus P = 0.032), particularly between October and April in women (P = 0.001) and October and January in men (P = 0.05). The ApoB/ApoA-I ratio in female CWS decreased over the season (P = 0.02), particularly between October and January (P = 0.05), and a trend toward the TG concentration to reduce over the swimming season was also observed in female CWS. No beneficial changes were noticed in the control group over the season. Our results suggest that the favorable effect of cold swimming on the cardiovascular risk factors may be gender-dependent; further studies are thus needed to draw a precise conclusion.
AbstractBackgroundChediak–Higashi syndrome (CHS) is a rare and potentially fatal autosomal recessive disease characterized by frequent bacterial infections, bleeding tendency, oculocutaneous ...albinism, photosensitivity and progressive neurologic dysfunction. Owing to the rarity of this condition, the objective of this study was to describe patients with CHS. MethodsRetrospective evaluation of patients followed in a paediatric tertiary centre of Allergy and Immunology of São Paulo, Brazil, between 1986 and 2018 with a confirmed diagnosis of CHS. Data were obtained from medical records. Demographic aspects, family history, clinical findings, laboratory data, diagnosis, treatment and outcome were described. ResultsA total of 14 patients (five male) were included. Clinical manifestations were first recognized at a median age of two months (at birth-20 months). Median age at diagnosis was 1.7 years (0–5 years). All patients had recurrent infections. Albinism was present in 13 patients and silvery or light hair was present in 14. Seven patients developed hemophagocytic lymphohistiocytosis (HLH); the median age at the diagnosis of HLH was 5.7 years (2.6–6.7 years) and the median interval between the diagnosis of CHS and HLH was 3.3 years (0–5 years). Four of the most recently diagnosed patients underwent bone marrow transplantation (BMT). Nine patients are deceased, and one was lost to follow-up. The median age of death was 6.7 years (3.8–22 years). Five patients died of HLH, one of lymphoma, and three of infection. All the patients who had HLH before the year of 2000 died of HLH. The two most recently diagnosed patients with HLH were able to cure the HLH, although they died of other causes. Four patients are alive, three of them after successful BMT. ConclusionThirty years of follow up showed an improvement in the prognosis in patients with CHS. The better understanding of the underlying biological mechanisms of HLH allowed the standardization of management protocols, resulting in survival improvement. BMT is the only treatment that can change CHS prognosis, which emphasizes the need for early identification of the disease.
Abstract Background Determining whether patients with cow's milk allergy (CMA) can tolerate foods produced with baked milk could provide a better quality of life, a better prognosis, and an option ...for desensitization. Objectives The aim of this study was to identify which patients over four years of age with persistent CMA could tolerate baked milk, to compare the clinical and laboratory characteristics of reactive and non-reactive groups and to describe their clinical evolution. Materials and methods A cross-sectional study was conducted (January/13 to November/14) that included all the patients followed at a food allergy center who met the inclusion criteria. The patients underwent an oral food challenge (OFC) with a muffin (2.8 g of cow's milk protein). To exclude cow's milk (CM) tolerance, the patients were subsequently challenged with unheated CM. Results Thirty patients met all the inclusion criteria. Fourteen patients (46.7%) were considered non-reactive to baked milk and reactive to unheated CM. When the groups that were reactive and non-reactive to baked milk were compared, no statistically significant differences in clinical features were found. The prick test for α-lactalbumin ( p = 0.01) and casein ( p = 0.004) and the serum specific IgE for casein ( p = 0.05) presented statistical differences. After one year, none of the patients who were reactive to baked milk were ingesting CM, while 28% of the tolerant patients were consuming fresh CM ( p = 0.037). Conclusions Baked milk can be tolerated by patients with CMA, especially those with lower levels of casein and α-lactalbumin. This option can improve quality of life and accelerate tolerance.
Background
Ulcerative colitis (UC) is often associated with nutritional deficiency, which appears to contribute to the progression of UC severity. The present study aimed to evaluate nutritional ...status and dietary intake in UC remission patients.
Methods
The present study comprised a cross‐sectional study in which variables such as extent of disease (distal colitis, left‐sided colitis, pancolitis), remission period, sex and age were recorded. Extent of disease was assessed by the results of a colonoscopy and dietary intake was evaluated by using 3‐day, 24‐h recalls. A Kruskall–Wallis test was used to compare the intake of macro‐ and micronutrients among the three study groups. The analysis was complemented by the Mann–Whitney test. A logistic regression analysis was performed to identify predictive factors of extent of disease (pancolitis versus left‐sided colitis versus distal colitis).
Results
The median (range) age of the 59 patients was 49.0 (37.0–63.0) years and 53.3% were female. Twenty‐six (44.1%) patients had distal colitis, 11 (18.6%) patients had left‐sided colitis and 22 (37.3%) patients had pancolitis. A high probability of an inadequate intake of fibre (100%), fat soluble vitamins (>40% for vitamin A and >95% for vitamin E), vitamin C (>34%), calcium (>90%) and magnesium (>50%) was identified in the study group. Vitamin D intake (odds ratio = 0.60; 95% confidence interval = 0.39–0.94; P < 0.05) was significantly associated with increased intestinal damage.
Conclusions
A large number of individuals showed an inadequate intake of nutrients. In addition, the consumption of vitamin D was significantly associated with extent of disease.
Adeno Associated virus serotype 8 (AAV8) is of particular interest as a vector for pre-clinical and clinical trial for Duchenne Muscular Dystrophy (DMD). In several cell lines, this vector has been ...shown to enter cells through clathrin-mediated endocytosis followed by a trafficking through the microtubule network in various endosomal compartments toward the nucleus. To efficiently transduce cells, AAV must undergo multiple levels of regulation in these cellular compartments. In DMD, dystrophin deficiency results in disturbed balance of cellular events i.e., fiber centronucleation, disorganized cytoskeleton, presence of fibrosis. We have recently described a loss of virion genomes from both dogs and mice models of DMD treated with therapeutic molecules vectorized in AAV. Indeed, the pathophysiological state of DMD muscle should impact on virions fate and subsequently affect crucial steps for AAV effectiveness as viral uncoating, viral genome maintenance and consequently, the transduction efficiency of AAV. Our project aims to characterize cellular uptake and intracellular transport of AAV8 in DMD muscular cells, with the goal of optimizing AAV vector use to get the best transduction efficiency with the lowest AAV dose. Our first data showed that AAV8-GFP was less efficient to transduce DMD and control primary muscular cells compared to HeLa cells. Moreover, AAV8 traffics through same endosomal compartment in DMD and control myoblasts, but at different rates during early time points of the transduction. These results suggest that in muscle cells, AAV8 uses different entry and trafficking pathways from those previously described in HeLa cells and that dystrophic cellular status could affect subcellular processing of the vector particles. We will specify the relationship between AAV8 vector entry, trafficking, uncoating, and transduction efficiency in vitro in primary myoblasts/myotubes of DMD patients and controls.
Background
Chronic hepatitis C causes chronic hepatic inflammation, which can lead to cirrhosis, terminal liver failure, and hepatocellular carcinoma. The treatment aims to achieve viral clearance, ...but the usage of pegylated interferon and ribavirin is linked to side effects such as severe weight loss, which can lead to complications and treatment discontinuation. The aim of this study was to investigate which anthropometric measures were more affected in patients with chronic hepatitis C during 24 weeks of treatment with pegylated interferon and ribavirin. Then, the influence of age, sex, hepatic fibrosis stage, and ribavirin doses on each measure was also evaluated.
Methods
Seventy-six patients were included and their weight, triceps skin fold thickness, arm circumference, middle-arm muscle circumference, and corrected arm muscle area were measured before and after 24 weeks of treatment. Epidemiological data and liver biopsy findings were obtained from patients’ records. The sample was divided into two groups: one with advanced hepatic fibrosis and another group with mild to moderate fibrosis. Comparisons into each group were made using Wilcoxon or paired
t
tests. After that, a linear regression model was applied to estimate the anthropometric changes during the treatment according to age, sex, hepatic fibrosis stage, and ribavirin doses.
Results
The subjects suffered reductions of important anthropometric measures, mainly related to fat mass (
p
< 0.001). Some decrease of fat-free mass was also observed in subjects with advanced fibrosis. The statistic model showed that age and sex were more associated with the anthropometric changes observed.
Conclusions
In conclusion, the antiviral treatment caused loss of relevant anthropometric measures, and the model proposed was able to estimate some of them.
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