Effect of particle size on the surface properties and morphology of ground flax

Flax fibers were ground with a ball-mill and four fractions with different size ranges were collected by sieving. These were tested for water sorption, degree of polymerization (DP), copper number, hydroxyl number and analyzed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and inverse gas chromatography (IGC). Significant differences were found between the properties of the flax fiber and those of the ground versions, including fragmentation of fibers, increase of water sorption, copper number, hydroxyl number and surface O/C ratio, and decrease of DP, crystallite size and dispersive component of surface energy (gammasd). Some parameters depended on the particle size: O/C ratio and hydroxyl number had local maxima at 315-630 μm, while gammasd increased steadily with the decrease of particle size. These relationships were explained by fiber disintegration, destruction of waxy surface layer, exposure of cellulosic components, increase of surface area and crystalline imperfections

A salsolinol dopaminerg transzmisszióban betöltött fiziológiás szerepének vizsgálata = Examination of the physiological role of salsolinol in dopaminergic neurotransmission

Korábban kimutattuk, hogy a hipofízis közti-hátsó lebenyének (NIL) prolaktin (PRL) ürítő hatásért a salsolinol (SAL) felelős. A PRL-szint emelkedéssel párhuzamosan a SAL az eminentia medianaban (ME) csökkenti, míg az elülső lebenyben (AL) növeli cAMP szintet. A SAL-nak egy szerkezeti analógja, az 1MeDIQ képes gátolni a szopási ingerre és a stresszre bekövetkező PRL szint emelkedést. Mindezek alátámasztják korábbi feltevésünket, hogy a SAL az a régóta keresett élettanilag is jelentős prolaktoliberin. Az 1MeDIQ az amfetamin (AMPH)-hoz hasonló psziho-stimuláns hatással is rendelkezik, növeli a plazma katecholamin-szinteket. A perifériás szimpatikus beidegzések műtéti vagy farmakológiás (chlorisondamine) lézióját követően fellépő változások a SAL hatásában világosan jelzik, hogy az 1MeDIQ hatásában a norepinefrin (NE)-erg rendszer kulcsszerepet játszik. A PRL felszabadító hatása mellett a SAL csökkenti a stressz és az 1MeDIQ kiváltotta plazma NE és epinefrin (E) emelkedést. Hasonló kölcsönhatást találtunk az AMPH és a SAL prolaktin elválasztásra gyakorolt hatásában is. A szimpatikus idegelemek által beidegzett szervekben, mint a pitvarban, lépben, májban, vagy az ovariumban, a SAL szelektíven csökkenti a dopamin (DA) koncentrációját. SAL-nak ez a hatása a kivédhető AMPH-előkezeléssel. Összefoglalva, a SAL és az AMPH között kölcsönhatás állapítható meg az elülső lebenyi PRL-ürítés és a szimpatikus végződésekben zajló katecholamin-metabolizmus vonatkozásában egyaránt. | We have previously shown that salsolinol (SAL) is responsible for the prolactin (PRL) releasing activity detected in the neurointermediate lobe (NIL) of the pituitary gland. SAL can induce a decrease of cAMP level in the median eminence (ME) and an increase in the anterior lobe (AL). A structural analogue of SAL, 1MeDIQ, can inhibit the elevation of plasma PRL induced by physiological stimuli like suckling or stress. All these data support our assumption that SAL may be the physiologically relevant prolactoliberin. 1MeDIQ has a psycho-stimulant action as well, which is similar to the effect of amphetamine (AMPH) i.e. induces an increase in plasma catecholamine concentrations. Surgical or pharmacological (chlorisondamine) lesions of peripheral sympathetic innervations clearly indicate that norepinephrin (NE)-erg system has pivotal role in the action of 1MeDIQ. SAL, besides its PRL releasing activity, can significantly decrease stress and 1MeDIQ induced increase in plasma NE and epinephrine (E) levels. There is an interaction between AMPH and SAL on pituitary PRL release too. SAL treatment results in a selective decrease in DA content of sympathetically innervated organs like atrium, spleen, liver, ovaries, and salivary gland. This effect of SAL is prevented by AMPH pretreatment. It is clear that there is a mutual interaction between SAL and AMPH not only on PRL release, but their interaction is obvious on the catecholamine ?metabolism? of nerve terminals as well

Safety and Efficacy of Weekly 30,000 IU Vitamin D Supplementation as a Slower Loading Dose Administration Compared to a Daily Maintenance Schedule in Deficient Patients: a Randomized, Controlled Clinical Trial

L

Exercise Effects on Multiple Sclerosis Quality of Life and Clinical-Motor Symptoms

Introduction Different therapies can improve clinical and motor symptoms of multiple sclerosis (MS) similarly, but studies comparing the effects of different exercise therapies on clinical and motor outcomes are scant. We compared the effects of exergaming (EXE), balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group (CON) on clinical and motor symptoms and quality of life (QoL) in people with MS (PwMS). Methods PwMS (n = 68, 90% female; age, 47.0 yr; Expanded Disability Status Scale score 5-6) were randomized into five groups. Before and after the interventions (five times a week for 5 wk), PwMS were tested for MS-related clinical and motor symptoms (Multiple Sclerosis Impact Scale-29 (MSIS-29), primary outcome), QoL (EuroQol Five Dimensions Questionnaire), symptoms of depression, gait and balance ability (Tinetti Assessment Tool), static and dynamic balance and fall risk (Berg Balance Scale), walking capacity (6-min walk test), and standing posturography on a force platform. Results EXE, BAL, and CYC improved the MSIS-29 scores similarly. EXE and CYC improved QoL and walking capacity similarly but more than BAL. Only EXE improved gait and balance scores (Tinetti Assessment Tool). EXE and BAL improved fall risk and standing balance similarly but more than CYC. PNF and CON revealed no changes. The EuroQol Five Dimensions Questionnaire moderated the exercise effects on the MSIS-29 scores only in EXE. Changes in QoL and changes in the MSIS-29 scores correlated (R2 = 0.73) only in EXE. Conclusion In conclusion, BAL and CYC but EXE in particular, but not PNF, can improve clinical and motor symptoms and QoL in PwMS (Expanded Disability Status Scale score 5 to 6), expanding the evidence-based exercise options to reduce mobility limitations in PwMS

High Frequency and Intensity Rehabilitation in 641 Subacute Ischemic Stroke Patients

Objectives: To determine the effects of exergaming on quality of life (QoL), motor, and clinical symptoms in subacute stroke patients. Design: A pseudorandomized controlled trial, using a before-after test design. Setting: University hospital. Participants: Subacute, ischemic stroke outpatients (N=3857), 680 of whom were randomized and 641 completed the study. Interventions: We determined the effects of 5 times a week twice daily (EX2; 50 sessions; n=286) and once daily (EX1; 25 sessions; n=272) exergaming and low-intensity standard care (control [CON]; 25 sessions; n=83) on clinical, mobility, blood pressure (BP), and QoL outcomes. Main Outcome Measures: The primary outcome was Modified Rankin Scale. Secondary outcomes were activities of daily living, 5 aspects of health-related QoL, Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), and static balance (center of pressure). Results: During exercise, the peak heart rate was 134, 134, and 126 beats per minute in the EX2, EX1, and CON groups, respectively. mRS improved similarly in the EX2 (–1.8; effect size, d=–4.0) and EX1 (–1.4; d=–2.6) groups, but more than in the CON group (–0.7; d=–0.6). QoL, Barthel Index, BBS, 6MWT, and standing posturography improved more in the EX2 group and the same in the EX1 and CON groups. Systolic and diastolic resting BP decreased more in the EX2 and EX1 groups than in the CON group. The intervention effects did not differ between men (n=349) and women (n=292). Conclusions: Twice daily compared with once daily high-intensity exergaming or once daily lower intensity standard care produced superior effects on clinical and motor symptoms, BP, and QoL in male and female subacute ischemic stroke participants

Angiotensin Receptor Neprilysin Inhibition Compared With Enalapril on the Risk of Clinical Progression in Surviving Patients With Heart Failure

BACKGROUND: -Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: -We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensinconverting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-Btype natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: -Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255

Risk Related to Pre-Diabetes Mellitus and Diabetes Mellitus in Heart Failure With Reduced Ejection Fraction: Insights From Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial

BACKGROUND: The prevalence of pre-diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: /=6.5% [>/=48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52; P6.5%) and known diabetes mellitus compared with those with HbA1c<6.0% was 1.39 (1.17-1.64); P<0.001 and 1.64 (1.43-1.87); P<0.001, respectively. Patients with pre-diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10-1.47]; P<0.001) compared with those with HbA1c<6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. CONCLUSIONS: In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre-diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c <6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255

Detection of methylated septin 9 in tissue and plasma of colorectal patients with neoplasia and the relationship to the amount of circulating cell-free DNA

BACKGROUND: Determination of methylated Septin 9 (mSEPT9) in plasma has been shown to be a sensitive and specific biomarker for colorectal cancer (CRC). However, the relationship between methylated DNA in plasma and colon tissue of the same subjects has not been reported. METHODS: Plasma and matching biopsy samples were collected from 24 patients with no evidence of disease (NED), 26 patients with adenoma and 34 patients with CRC. Following bisulfite conversion of DNA a commercial RT-PCR assay was used to determine the total amount of DNA in each sample and the fraction of mSEPT9 DNA. The Septin-9 protein was assessed using immunohistochemistry. RESULTS: The percent of methylated reference (PMR) values for SEPT9 above a PMR threshold of 1% were detected in 4.2% (1/24) of NED, 100% (26/26) of adenoma and 97.1% (33/34) of CRC tissues. PMR differences between NED vs. adenoma and NED vs. CRC comparisons were significant (p<0.001). In matching plasma samples using a PMR cut-off level of 0.01%, SEPT9 methylation was 8.3% (2/24) of NED, 30.8% (8/26) of adenoma and 88.2% (30/34) of CRC. Significant PMR differences were observed between NED vs. CRC (p<0.01) and adenoma vs. CRC (p<0.01). Significant differences (p<0.01) were found in the amount of cfDNA (circulating cell-free DNA) between NED and CRC, and a modest correlation was observed between mSEPT9 concentration and cfDNA of cancer (R2 = 0.48). The level of Septin-9 protein in tissues was inversely correlated to mSEPT9 levels with abundant expression in normals, and diminished expression in adenomas and tumors. CONCLUSIONS: Methylated SEPT9 was detected in all tissue samples. In plasma samples, elevated mSEPT9 values were detected in CRC, but not in adenomas. Tissue levels of mSEPT9 alone are not sufficient to predict mSEPT9 levels in plasma. Additional parameters including the amount of cfDNA in plasma appear to also play a role

Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory

SHMT1 1420 and MTHFR 677 variants are associated with rectal but not colon cancer

<p>Abstract</p> <p>Background</p> <p>Association between rectal or colon cancer risk and serine hydroxymethyltransferase 1 (<it>SHMT1</it>) C1420T or methylenetetrahydrofolate reductase (<it>MTHFR</it>) C677T polymorphisms was assessed. The serum total homocysteine (HCY), marker of folate metabolism was also investigated.</p> <p>Methods</p> <p>The <it>SHMT1 </it>and <it>MTHFR </it>genotypes were determined by real-time PCR and PCR-RFLP, respectively in 476 patients with rectal, 479 patients with colon cancer and in 461 and 478, respective controls matched for age and sex. Homocysteine levels were determined by HPLC kit. The association between polymorphisms and cancer risk was evaluated by logistic regression analysis adjusted for age, sex and body mass index. The population stratification bias was also estimated.</p> <p>Results</p> <p>There was no association of genotypes or diplotypes with colon cancer. The rectal cancer risk was significantly lower for <it>SHMT1 </it>TT (OR = 0.57, 95% confidence interval (CI) 0.36-0.89) and higher for <it>MTHFR </it>CT genotypes (OR = 1.4, 95%CI 1.06-1.84). A gene-dosage effect was observed for <it>SHMT1 </it>with progressively decreasing risk with increasing number of T allele (p = 0.014). The stratified analysis according to age and sex revealed that the association is mainly present in the younger (< 60 years) or male subgroup. As expected from genotype analysis, the <it>SHMT1 </it>T allele/<it>MTHFR </it>CC diplotype was associated with reduced rectal cancer risk (OR 0.56, 95%CI 0.42-0.77 vs all other diplotypes together). The above results are unlikely to suffer from population stratification bias. In controls HCY was influenced by <it>SHMT1 </it>polymorphism, while in patients it was affected only by Dukes' stage. In patients with Dukes' stage C or D HCY can be considered as a tumor marker only in case of <it>SHMT1 </it>1420CC genotypes.</p> <p>Conclusions</p> <p>A protective effect of <it>SHMT1 </it>1420T allele or <it>SHMT1 </it>1420 T allele/<it>MTHFR </it>677 CC diplotype against rectal but not colon cancer risk was demonstrated. The presence of <it>SHMT1 </it>1420 T allele significantly increases the HCY levels in controls but not in patients. Homocysteine could be considered as a tumor marker in <it>SHMT1 </it>1420 wild-type (CC) CRC patients in Dukes' stage C and D. Further studies need to clarify why <it>SHMT1 </it>and <it>MTHFR </it>polymorphisms are associated only with rectal and not colon cancer risk.</p