Sodium and Potassium Intake of Urban Dwellers: Nothing Changed in Yazd,Iran

To assess the daily salt intake of people aged 20-74 years based on the 24-hour urinary sodium excretion in urban population of Yazd, a population-based cross-sectional study was conducted. This is a substudy of Yazd Healthy Heart Project in Iran. From 2004 to 2005, two thousand people of the urban population of Yazd city, aged 20-74 years, were enrolled in the main study. Overall, 219 volunteer participants of 20-70 years were enrolled in this substudy. Sample frame was the household numbers according to the database of Yazd City Health Services. Calcium, phosphorus, sodium, potassium, and creatinine were measured in the urine samples collected from the participants over a 24-hour period. Sodium content in urine over 24 hours was 171.7±82.9 mmol/day in males and 127.8±56.1 mmol/day in females (p<0.0001) while potassium content was 49.4±23.2 mmol/day in males and 41.5±25.1 mmol/day in females (p=0.2). Estimated average daily salt (NaCl) intake was 10.0±4.8 g/day in males and 7.5±3.3 g/day in females (p<0.0001). Only one participant had the ideal Na/K ratio of less than one. Na/K ratios greater than one and less than two were seen in 11.3% (n=24), and a ratio equal to or greater than 2 was observed in 82.3% (n=118) of the participants. The average Na/K ratio was 3.69±1.58. Unlike many developed countries where sodium intake declined over the past few decades, the daily sodium intake in Yazd is high, and daily potassium intake is low. This is similar to what was observed four decades ago in an area not far from Yazd. Efforts must be directed towards health promotion interventions to increase public awareness to reduce sodium intake and increase potassium intake.Key words: 24-hour urine, Blood pressure, Cardiovascular disease, Hypertension, Policy, Potassium, Prevention, Salt, Sodium, Iran     

Atherogenic consequence of antiepileptic drugs: a study of intima-media thickness

We intended to evaluate the carotid intima-media thickness (CA-IMT) as a surrogate factor for atherogenesis in epileptic patients on enzyme inducer (EI) antiepileptic drugs (AEDs) or valproate (VA). The study included 71 patients with epilepsy (37 females) aged 27.7 ± 8.1 and 71 age- and sex-matched non-epileptic subjects. Patients with history of at least 2 years antiepileptic treatment were enrolled. Subjects with known history of cardiovascular risk factors were not included. Thirty-eight patients (21 females) were treated with EI medications and 33 (16 females) with VA. CA-IMTs were measured by a single sonography system in all participants. CA-IMT values were compared between patients with epilepsy and the controls and within the patients with epilepsy on VA or EI medications. Duration of epilepsy was 10.1 ± 7.1 years. Patients were treated with their current AED for 6.9 ± 4.8 years. The CA-IMT of patients with epilepsy was higher than non-epileptic control subjects on either left (0.502 ± 0.079 vs. 0.470 ± 0.073 mm; p = 0.012) or right side (0.524 ± 0.078 vs. 0.458 ± 0.068 mm; p < 0.001). Patients on VA were younger than those receiving EI medications (25.8 ± 7.1 vs. 29.4 ± 8.7 years). Age adjusted CA-IMT values of patients on VA did not differ from the values of patients receiving EI medications. Duration of drug administration did not correlate with CA-IMT values. Patients with epilepsy on AEDs are at higher risk for atherogenesis. In the population of this study the increased risk of atherogenesis was not attributable to the administered AED or duration of treatment.     

Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms

Amyotrophic lateral sclerosis (ALS) is predominantly sporadic, but associated with heritable genetic mutations in 5–10% of cases, including those in Cu/Zn superoxide dismutase (SOD1). We previously showed that misfolding of SOD1 can be transmitted to endogenous human wild-type SOD1 (HuWtSOD1) in an intracellular compartment. Using NSC-34 motor neuron-like cells, we now demonstrate that misfolded mutant and HuWtSOD1 can traverse between cells via two nonexclusive mechanisms: protein aggregates released from dying cells and taken up by macropinocytosis, and exosomes secreted from living cells. Furthermore, once HuWtSOD1 propagation has been established, misfolding of HuWtSOD1 can be efficiently and repeatedly propagated between HEK293 cell cultures via conditioned media over multiple passages, and to cultured mouse primary spinal cord cells transgenically expressing HuWtSOD1, but not to cells derived from nontransgenic littermates. Conditioned media transmission of HuWtSOD1 misfolding in HEK293 cells is blocked by HuWtSOD1 siRNA knockdown, consistent with human SOD1 being a substrate for conversion, and attenuated by ultracentrifugation or incubation with SOD1 misfolding-specific antibodies, indicating a relatively massive transmission particle which possesses antibody-accessible SOD1. Finally, misfolded and protease-sensitive HuWtSOD1 comprises up to 4% of total SOD1 in spinal cords of patients with sporadic ALS (SALS). Propagation of HuWtSOD1 misfolding, and its subsequent cell-to-cell transmission, is thus a candidate process for the molecular pathogenesis of SALS, which may provide novel treatment and biomarker targets for this devastating disease.Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular condition that afflicts as many as 1 of 350 males and 420 females over the age of 18 (1). In ALS, degeneration of upper and lower motor neurons causes progressive muscle paralysis and spasticity, affecting mobility, speech, swallowing, and respiration (2). Half of affected individuals die within 3 y, and less than 20% survive for more than 5 y (3); 90–95% of ALS cases are sporadic (SALS) in which some apparently facilitating gene mutations, such as repeat expansions in the gene that encodes ataxin-2 (4), have been identified. The remaining 5–10% of ALS cases are familial (FALS) and predominantly associated with Mendelian-inherited mutations in the genes encoding Cu/Zn superoxide dismutase (SOD1), TAR-DNA–binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), C9ORF72, and other genes (reviewed in ref. 3).Despite the profusion of functionally diverse genes implicated in FALS and SALS, clinical and pathological similarities between all forms of ALS suggest the existence of a common pathogenic pathway that could be united by a single gene/protein (5). One of the mechanisms by which a mutant or wild-type (WT) protein can dominate pathogenesis of phenotypically diverse diseases is by propagated protein misfolding, such as that underpinning the prion diseases, which has been increasingly implicated in other neurodegenerative and systemic disorders (6, 7). A role for propagated protein misfolding in ALS is supported by the prion-like spatiotemporal progression of disease through the neuroaxis (8, 9). However, given the disparity in protein inclusion pathology between subtypes of ALS, a single unifying prion-like protein that could explain such a progression remains obscure.Whereas it is generally accepted SOD1 is not found in large perikaryal cytoplasmic inclusions outside of SOD1 FALS cases, misfolded SOD1 has been increasingly identified in SALS and non-SOD1 FALS (5, 10, 11). Indeed, we have reported that misfolded human wild-type SOD1 (HuWtSOD1) can be detected by spinal cord immunohistochemistry (IHC) in FALS secondary to FUS mutation, and in SALS patients with cytosolic WT TDP-43 accumulation (11). Moreover, in cell models, overexpression of WTTDP-43, or expression of mutant FUS or TDP-43, is associated with HuWtSOD1 misfolding (11). Collectively, these data are consistent with SOD1 being a molecular common denominator for all types of ALS. Furthermore, prion-like activity has been described for the cell-to-cell transmission of misfolding of mutant SOD1 (12), and we have reported that mutant SOD1 can confer its misfold on HuWtSOD1 (13). However, mutant SOD1 cannot explain propagation in SALS.To test if HuWtSOD1 participates in cell-to-cell transmission of protein misfolding, we make use of previously developed mouse mAb probes for misfolded/oxidized SOD1, recognizing either full-length human mutant or WT SOD1, generated against regions that are antibody-inaccessible in natively folded SOD1 (13–15). Misfolded SOD1 mAbs used in this work are 10E11C11 and 3H1, directed against an unstructured electrostatic loop [disease-specific epitope-2 (DSE2)], and 10C12, directed against a C-terminal dimer interface peptide in which the cysteine at position 146 is substituted by a cysteic acid residue to mimic oxidation of this residue (DSE1a) (13). The use of such antibody probes have enabled us to unambiguously determine the role of misfolded mutant G127X in the induced misfolding of HuWtSOD1, which upon misfolding acquires a marked increase in sensitivity to protease digestion, consistent with global loosening of structure (13). The finding that misfolded endogenous HuWtSOD1 was observed long after transfected G127X-SOD1 was degraded suggested that HuWtSOD1, once misfolded, is capable of triggering an intracellular propagated misfolding reaction (13). We now report for the first time that misfolded HuWtSOD1 can transit cell to cell both via exosomes, and release of protein aggregates and subsequent uptake in neuronal cells. In addition, misfolded HuWtSOD1 can sustain intercellular propagated misfolding in vitro and is detectable in the spinal cord of all ALS patients tested, regardless of the genetic etiology of the disease. Collectively, these data indicate that HuWtSOD1 is competent to participate in propagated misfolding, suggesting a common pathogenic mechanism linking FALS and SALS.     

Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a

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Antioxidant effects of oleuropein versus oxidative stress induced by ethanol in the rat intestine

Purified oleuropein from olive leaf extract indicated antioxidant properties in our previous reports. The recent study demonstrated that the lesions of absolute ethanol could be attributed to the increasing reactive oxygen species, subsequently lipid peroxidation and gastric ulcers. Therefore, the antioxidant effects of oleuropein as a natural antioxidant agent on intestine mucosal damages induced by absolute ethanol were investigated in the present study. The 42 adult male rats were divided into four (control, oleuropein, ethanol, and oleuropein plus ethanol) groups. Oleuropein at a dosage of 12 mg/kg was used for 10 consecutive days in oleuropein and oleuropein plus ethanol groups, thereafter absolute ethanol (once, 1 ml/rat) was administrated orally in ethanol and oleuropein plus ethanol groups at fasting state by gavage. The duodena of rats were removed for histopathology and antioxidant assay. Histological evidence of severe mucosal damages were confirmed by histopathology findings in ethanol group and prevented in oleuropein plus ethanol group. In this setting, glutathione peroxidase and catalase activities were significantly higher in oleuropein and oleuropein plus ethanol groups than the ethanol-treated rats. In contrast, thiobarbituric acid reactive substances concentration (as a lipid peroxidation marker) significantly increased in ethanol-treated rats when compared to the other groups. Our results suggest that olive leaf extract (containing oleuropein) exerts a potent antioxidant agent against oxidative stress. These findings allow us to exploit the advantages of oleuropein treatment in various diseases induced by oxidative stress in humans.     

Influence of Apical Periodontitis on the Accuracy of 3 Electronic Root Canal Length Measurement Devices: An In Vivo Study

Introduction

The aim of this in vivo study was to evaluate the influence of apical periodontitis (AP) on the accuracy of Dentaport ZX (J Morita, Kyoto, Japan), Raypex 5 (VDW, Munich, Germany), and i-Root (S-Denti, Seoul, Korea) electronic root canal length measurement devices (ERCLMDs).

Methods

Thirty-two single-rooted teeth scheduled for extraction, consisting of 16 teeth with AP and 16 teeth with normal periapex (NP), were selected. The access cavity was prepared, and the coronal portion of the canal was flared. The electronic working length (EWL) was determined by each ERCLMD according to each manufacturer's instructions. Each tooth was extracted, and the actual working length (AWL) was determined by inserting a size 15 K-file until the tip could be seen at a position tangential to the major foramen and then 0.5 mm was subtracted from the measurement. The distance from the file tip (EWL) to the point 0.5 mm coronal to the major foramen (AWL) was calculated. Data were analyzed using the nonparametric Fisher exact test and the chi-square test. Statistical significance was set at P < .05.

Results

The accuracies of Dentaport ZX, Raypex 5, and i-Root within ±0.5 mm in the AP group were 93.8%, 81.3%, and 75.0%; they were 93.3%, 86.7%, and 73.3% in the NP group, respectively. There were no significant differences between the accuracy of each device in the 2 groups (P > .05). Considering the 2 groups of AP and NP, there were no statistically significant differences in the accuracy of the ERCLMDs (P > .05).

Conclusions

The presence of AP did not influence the accuracy of ERCLMDs.     

Identification of novel variants in Iranian consanguineous pedigrees with nonsyndromic hearing loss by next-generation sequencing

BackgroundThe extremely high genetic heterogeneity of hearing loss due to diverse group of genes encoding proteins required for development, function, and maintenance of the complex auditory system makes the genetic diagnosis of this disease challenging. Up to now, 121 different genes have been identified for nonsyndromic hearing loss (NSHL), of which 76 genes are responsible for the most common forms of NSHL, autosomal recessive nonsyndromic hearing loss (ARNSHL).MethodsAfter excluding mutations in the most common ARNSHL gene, GJB2, by Sanger sequencing, genetic screening for a panel of genes responsible for hereditary hearing impairment performed in 9 individuals with ARNSHL from unrelated Iranian consanguineous pedigrees.ResultsOne compound heterozygote and eight homozygote variants, of which five are novel, were identified: CDH23:p.(Glu1970Lys), and p.(Ala1072Asp), GIPC3:p.(Asn82Ser), and (p.Thr41Lys), MYO7A:p.[Phe456Phe]; p.[Met708Val], and p.(Gly163Arg), TECTA:p.(Leu17Leufs*19), OTOF:c.1392+1G>A, and TRIOBP:p.(Arg1068*). Sanger sequencing confirmed the segregation of the variants with the disease in each family.ConclusionFinding more variants and expanding the spectrum of hearing impairment mutations can increase the diagnostic value of molecular testing in the screening of patients and can improve counseling to minimize the risk of having affected children for at risk couples.     

Preparation and optimization of activated nano-carbon production using physical activation by water steam from agricultural wastes

Production of activated nano-carbon from agricultural wastes was studied in this work. To obtain the optimum production conditions by a physical activation method, influence of temperature (850, 900, 950 and 1000 °C), activation residence time (30, 60 and 90 min), and mill rotation (200, 300 and 400 rpm) were investigated using three different raw materials including walnut, almond and pistachio shells. To prepare activated nano-carbon, all the samples were heated up to the final activation temperature under a continuous steam flow of 130 cm³ min⁻¹, and at a heating rate of 3 °C min⁻¹, and were held at the different activation temperatures for 30, 60 and 90 minutes. BET surface area of the obtained activated carbons was measured from nitrogen adsorption data in the relative pressure range between 0 to 1. Activated nano-carbon standard indexes were evaluated according to the ASTM standard and the samples were compared. First, the cellulose raw material was heated in the carbonization furnace at 600 °C and then activated in the advanced activation furnace at a temperature between 850 to 1000 °C for 30, 60 and 90 minutes with water vapor. Ash percentage, iodine content, moisture content, specific area, elemental analysis, and FESEM were used for product characterization. The results of the analysis showed that by using the water vapor physical activation method and optimizing the parameters of this process including time and rotation of the mill up to 10 min and 400 rpm, resulted in a significant increase in specific surface area, cavity volume and the iodine number of the final product.

Production of activated nano-carbon from agricultural wastes was studied in this work.