Low serum sodium concentration is an independent predictor of mortality in patients with cirrhosis, but its prevalence and clinical significance is unclear. To evaluate prospectively the prevalence ...of low serum sodium concentration and the association between serum sodium levels and severity of ascites and complications of cirrhosis, prospective data were collected on 997 consecutive patients from 28 centers in Europe, North and South America, and Asia for a period of 28 days. The prevalence of low serum sodium concentration as defined by a serum sodium concentration ≤135 mmol/L, ≤130 mmol/L, ≤125 mmol/L, and ≤120 mmol/L was 49.4%, 21.6%, 5.7%, and 1.2%, respectively. The prevalence of low serum sodium levels (<135 mmol/L) was high in both inpatients and outpatients (57% and 40%, respectively). The existence of serum sodium <135 mmol/L was associated with severe ascites, as indicated by high prevalence of refractory ascites, large fluid accumulation rate, frequent use of large‐volume paracentesis, and impaired renal function, compared with normal serum sodium levels. Moreover, low serum sodium levels were also associated with greater frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome, but not gastrointestinal bleeding. Patients with serum sodium <130 mmol/L had the greatest frequency of these complications, but the frequency was also increased in patients with mild reduction in serum sodium levels (131‐135 mmol/L). In conclusion, low serum sodium levels in cirrhosis are associated with severe ascites and high frequency of hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome. (HEPATOLOGY 2006;44:1535–1542.)
A mechanism of anesthesia has recently been proposed which predicts that coreleased neurotransmitters may modulate neurotransmitter receptors for which they are not the native agonist in a manner ...similar to anesthetics.
We tested this prediction by applying acetylcholine to a NR1/NR2A N-methyl-d-aspartate receptor, glycine to a wild-type alpha(1)beta(2) and anesthetic-resistant alpha(1)(S270I)beta(2) gamma-amino-butyric acid (GABA) type A receptor, and GABA to a homomeric alpha(1) wild type and anesthetic-resistant alpha(1) S267I glycine receptor. Receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping.
We found inhibition of N-methyl-d-aspartate receptor function by acetylcholine, enhancement of glycine receptor function by GABA, and enhancement of GABA type A receptor function by glycine. As expected of compounds with anesthetic activity, GABA showed far less potentiation (enhancement) of the function of the anesthetic-resistant S267I glycine receptor than that of the wild-type receptor. Glycine potentiated the function of wild-type GABA type A receptors but inhibited the function of the anesthetic-resistant S270I GABA type A receptor.
These results show that neurotransmitters that are coreleased onto anesthetic-sensitive receptors may modulate the function of receptors for which they are not the native agonist via an anesthetic-like mechanism. These findings lend support to a recent theory of anesthetic action.
Abstract We correct an overestimation of the production rate of $$^{137}$$ 137 Xe in the DARWIN detector operated at LNGS. This formerly dominant intrinsic background source is now at a level similar ...to the irreducible background from solar $$^8$$ 8 B neutrinos, thus unproblematic at the LNGS depth. The projected half-life sensitivity for the neutrinoless double beta decay ( $$0\nu \beta \beta $$ 0 ν β β ) of $$^{136}$$ 136 Xe improves by $$22\%$$ 22 % compared to the previously reported number and is now $$T^{0\nu }_{1/2}= {3.0\times 10^{27}} \hbox { yr}$$ T 1 / 2 0 ν = 3.0 × 10 27 yr (90% C.L.) after 10 years of DARWIN operation.
Objective. To investigate the construct validity and reliability of US DAS compared with 28-joint DAS (DAS-28) in assessing joint inflammation and in prediction of structural damage in patients with ...RA.
Methods. Ninety patients with active RA were prospectively recruited and followed up during the 6 months of treatment. The patients underwent clinical, laboratory and X-ray assessment, along with blinded power Doppler US (PDUS) and grey-scale (GS) US (GSUS) examination at baseline and 6 months. A subgroup of 25/90 randomly assigned patients underwent MRI examination of their hands at baseline. A PDUS examination of 22 joints and GSUS examination for effusion/hypertrophy (E/H) of 28 joints were performed by two independent examiners, blinded to clinical findings. E/H was qualitatively assessed as absent or present, and PD signal was semi-quantitatively graded from 0 to 3. PDUS score for synovitis in 22 joints and GS score for E/H in 28 joints were included in US DAS calculation. Clinical scoring, PDUS and GSUS inter-observer reliability were evaluated.
Results. Strong correlation was found between US DAS and standard assessment of disease activity such as the DAS-28, ESR and CRP levels. Correlation between US DAS and patients' and physicians' visual analogue scale of activity was moderate, whereas correlations of US DAS with Health Assessment Questionnaire - Disability Index (HAQ-DI) and Short Form 36 Health Survey (SF-36) were weak to moderate. US DAS correlated with X-ray, MRI and US parameters and rates of joint damage.
Conclusion. US DAS better anticipated future joint damage than standard DAS-28.
To investigate the contribution of central vasopressin receptors to blood pressure (BP) and heart rate (HR) response to stress we injected non-peptide selective V
1a (SR49059), V
1b (SSR149415), V
2 ...(SR121463) receptor antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious freely moving rats stressed by blowing air on their heads for 2
min. Cardiovascular effects of stress were evaluated by analyzing maximum increase of BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR curve (∫), duration of their recovery and spectral parameters of BP and HR indicative of increased sympathetic outflow (LF
BP and LF/HF
HR). Moreover, the increase of serum corticosterone was measured. Exposure to air-jet stress induced simultaneous increase in BP and HR followed by gradual decline during recovery while LF
BP oscillation remained increased as well as serum corticosterone level. Rats pre-treated with vasopressin receptor antagonists were not sedated while diazepam induced sedation that persisted during exposure to stress. V
1a, V
1b and V
2 receptor antagonists applied separately did not modify basal values of cardiovascular parameters but prevented the increase in ∫
BP. In addition, V
1b and V
2 receptor antagonists reduced BP
MAX whereas V
1a, V
1b antagonist and diazepam reduced HR
MAX induced by exposure to air-jet stress. All drugs shortened the recovery period, prevented the increase of LF
BP without affecting the increase in serum corticosterone levels. Results indicate that vasopressin receptors located within the central nervous system mediate, in part, the cardiovascular response to air-jet stress without affecting either the neuroendocrine component or inducing sedation. They support the view that the V
1b receptor antagonist may be of potential therapeutic value in reducing arterial pressure induced by stress-related disorders.
The DNA methylation pattern is an important component of the epigenome that regulates and maintains gene expression programs. In this paper, we test the hypothesis that vertebrate cells possess ...mechanisms protecting them from epigenomic stress similar to DNA damage checkpoints. We show that knockdown of DNMT1 (DNA methyltransferase 1) by an antisense oligonucleotide triggers an intra-S-phase arrest of DNA replication that is not observed with control oligonucleotide. The cells are arrested at different positions throughout the S-phase of the cell cycle, suggesting that this response is not specific to distinct classes of origins of replication. The intra-S-phase arrest of DNA replication is proposed to protect the genome from extensive DNA demethylation that could come about by replication in the absence of DNMT1. This protective mechanism is not induced by 5-aza-2'-deoxycytidine, a nucleoside analog that inhibits DNA methylation by trapping DNMT1 in the progressing replication fork, but does not reduce de novo synthesis of DNMT1. Our data therefore suggest that the intra-S-phase arrest is triggered by a reduction in DNMT1 and not by demethylation of DNA. DNMT1 knockdown also leads to an induction of a set of genes that are implicated in genotoxic stress response such as NF-kappaB, JunB, ATF-3, and GADD45beta (growth arrest DNA damage 45beta gene). Based on these data, we suggest that this stress response mechanism evolved to guard against buildup of DNA methylation errors and to coordinate inheritance of genomic and epigenomic information.
The use of family planning methods reduces maternal mortality, prevents unwanted and high-risk pregnancies, the need for (un)safe abortion and protects from sexually transmitted diseases. The ...objective of the study was to assess the use of family planning methods by women in the municipality of Nis. We applied an observational cohort study that included 1,584 women age 15-49 who lived in the municipality of Nis. Data was collected through the opinion poll examination, which took place in the municipality of Nis from February to September 2002. We found 81.9% of interviewees having sexual relations protect themselves from unwanted pregnancy permanently or occasionally; 18.1% do not. Of interviewees who do not use protection and have sexual relations, 28.1% think it harms health and 27.7% think it is unsafe. Among women who use contraceptive protection, 57.9% use traditional (unsafe) methods while 42.1% use modern methods. Interviewees who use contraception mostly choose a particular method of their own accord without consultation (52.9%); 58.2% estimate their method of contraception as partly safe, 6.8% as unsafe and 35% as completely safe. As to the reason for contraception use, 40.4% state they already have their preferred number of children, 22.4% use contraception for health reasons, 17% because they are not married, 7.6% because of poor economic condition, and other reasons are present in significantly lesser percentages. Of the interviewees, 29.3% had intentionally interrupted pregnancies. The use of family planning methods is unsatisfactory. Therefore, it is necessary to promptly begin promoting protection of reproductive health and the use of modern family planning methods as a part of the nurturing of healthy lifestyles.PUBLICATION ABSTRACT
Intravenous (IV) fluid bags made of polyvinyl chloride (PVC) often contain the plasticizer di(2-ethylhexyl) phthalate (DEHP) to make the PVC flexible. Phthalate esters have been reported to inhibit ...neuronal nicotinic acetylcholine receptors, which are sensitive to many inhaled anesthetics. This raises the possibility that DEHP might modulate the function of other cys-loop receptors, such as gamma-amino butyric acid type A (GABA(A)) and glycine receptors, and that DEHP-plasticized PVC might interfere with electrophysiologic studies of anesthetic mechanisms on those receptors.
alpha(1)beta(2) GABA(A) and alpha(1) glycine receptors were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. We then measured the effect of buffers from IV bags containing DEHP-plasticized PVC, and of buffers saturated with DEHP, on agonist-induced currents.
Agonist-induced currents from glycine receptors were enhanced by buffers from IV bags containing DEHP-plasticized PVC by 291.9% +/- 84.5% (mean +/- se) and from saturated solutions of DEHP by 70.8% +/- 16.7%. Agonist-induced currents from alpha(1)beta(2) GABA(A) receptors were inhibited by buffers from IV bags containing DEHP-plasticized PVC by 19.3% +/- 3.2% and by 31.7% +/- 7.0% from buffers saturated with DEHP.
The plasticizer DEHP modulates the function of both GABA(A) and glycine receptors. DEHP contamination can confound the results of electrophysiologic studies of anesthetic mechanisms on these receptors if DEHP-plasticized PVC is present in the experimental apparatus.
DNA methyltransferase 1 (DNMT1) catalyzes the post-replication methylation of DNA and is responsible for maintaining the DNA
methylation pattern during cell division. A long list of data supports a ...role for DNMT1 in cellular transformation and inhibitors
of DNMT1 were shown to have antitumorigenic effects. It was long believed that DNMT1 promoted tumorigenesis by maintaining
the hypermethylated and silenced state of tumor suppressor genes. We have previously shown that DNMT1 knock down by either
antisense oligonucleotides directed at DNMT1 or expressed antisense activates a number of genes involved in stress response
and cell cycle arrest by a DNA methylation-independent mechanism. In this report we demonstrate that antisense knock down
of DNMT1 in human lung carcinoma A549 and embryonal kidney HEK293 cells induces gene expression by a mechanism that does not
involve either of the known epigenomic mechanisms, DNA methylation, histone acetylation, or histone methylation. The mechanism
of activation of the cell cycle inhibitor p21 and apoptosis inducer BIK by DNMT1 inhibition is independent of the mechanism
of activation of the same genes by histone deacetylase inhibition. We determine whether DNMT1 knock down activates one of
the nodal transcription activation pathways in the cell and demonstrate that DNMT1 activates Sp1 response elements. This activation
of Sp1 response does not involve an increase in either Sp1 or Sp3 protein levels in the cell or the occupancy of the Sp1 elements
with these proteins. The methylation-independent regulation of Sp1 elements by DNMT1 unravels a novel function for DNMT1 in
gene regulation. DNA methylation was believed to be a mechanism for suppression of CG-rich Sp1-bearing promoters. Our data
suggest a fundamentally different and surprising role for DNMT1 regulation of CG-rich genes by a mechanism independent of
DNA methylation and histone acetylation. The implications of our data on the biological roles of DNMT1 and the therapeutic
potential of DNMT1 inhibitors as anticancer agents are discussed.
The application of industrial robots for machining is currently limited to tasks with low precision demands due to the low stiffness of industrial robots as compared to machine tools. This paper ...analytically describes an experiment-based compliance identification and analysis method for a 5- axis vertical articulated machining robot. An expansion of the conventional method for the calculation of the robot’s Cartesian space compliance that takes into consideration joint compliances and the Jacobian matrix is used. The analytical analysis considers the effects of the individual joint compliances on the resulting Cartesian space compliance. Experimentally, the Cartesian space compliance is obtained by direct measurement of the absolute displacements induced by static forces along 3-Cartesian directions at the tool tip from which the joint compliances are identified.
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