[Biomechanical study of anterior occipital condyle screw plate system].

Objective: To analyze the feasibility of anterior occipitocervical fusion biomechanical characteristic of craniovertebral reconstruction by anterior occipital condyle screw plate system. Methods: Six cervical vertebra specimens including 4 males and 2 females were enrolled, whose mean age of death was (49.3±7.5) years. The normal models were established by soft tissue dissection, and the instability models were established by destroy bone and ligament structure including, anterior arch of the atlas, part of the lateral mass of the atlas, the odontoid process, the odontoid apical ligament, the pterygoid ligament, the transverse ligament of the atlas the joint capsule. The clivus screw fixation models were established by anterior clivus screw fixation, and then those models were performed by anterior occipital condyle screw fixation. All four groups were loaded with a 1.5 N·m continuous pure force in flexion-extension, lateral bending, and axial rotation. Then measured the range of motion of specimen C0-C1 and C0-C2. And the pull-out force test was conducted to compare the effects of unicortical and bicortical fixation on the pull-out force of screws. Results: In the C0-C1 segment, the range of motion in flexion-extension (forward and posterior), lateral bending and axial rotation in the clivus group was 6.46°±0.85°, 5.14°±0.76°, 2.73°±0.36°, 1.12°±0.41°, respectively; and it was 5.92°±0.90°, 4.16°±1.06°, 2.86°±0.50°, 1.05°±0.27°, respectively in the occipital condyle group. As for C0-C2 segment, the range of motion in the clivus group was 9.55°±1.99°, 10.46°±2.03°, 6.90°±1.29°, 13.51°±1.37°, respectively; and it was 8.14°±1.38°, 9.53°±1.55°, 4.75°±1.06°, 7.90°±1.68°, respectively, in the occipital condyle group. The ranges of motion in the occipital condyle group were significantly lower than clivus group (all P<0.05). The maximum pull out force by bicortical fixation was significantly better than unicortical fixation ((439±33) N vs (408±28) N, P<0.05). Conclusion: The anterior occipital condyle screw plate system provides better stability especially in anti-bending and anti-rotation than the anterior clival screw fixation.

Association of serum uric acid change with mortality, renal function and diuretic dose administered in treatment of acute heart failure.

BACKGROUND AND AIMS: Hyperuricemia is reportedly associated with poor outcome in acute heart failure (AHF). The association between changes in Uric acid (UA) levels with renal function change, diuretic doses, and mortality in patients with AHF were studied. METHODS AND RESULTS: Consecutive patients hospitalized with AHF were reviewed (n = 535). UA levels were measured at admission and either at discharge or on approximately the seventh day of admission. Patients with an UA change in the top tertile were defined as having an increase (UA-increase) and were compared to those outside the top tertile (non-UA-increase). The endpoint was all-cause mortality, with a mean follow-up duration of 22.2 months. Patients in the UA-increase group presented with greater creatine increase (P < 0.001), and were administered a higher average daily dose of loop diuretic (P = 0.016) compared with the non-UA-increase group. In-hospital UA-increase was associated with higher risk of mortality even after adjusting for confounding variables including creatine change and diuretic dosage [harzard ratio (HR) 1.53, 95% confidence interval (CI) 1.02-2.30, P = 0.042]. In patients with hyperuricemia on admission, UA-increase was associated with increased mortality (adjusted HR 2.21, 95% CI 1.38-3.52, P = 0.001). Whereas, in those without admission hyperuricemia, UA-increase had no significant association with mortality. CONCLUSIONS: An increase in UA during in-hospital treatment is associated with an increase in creatine levels and daily diuretic dose. Mortality associated with increased UA is restricted to patients who already have hyperuricemia at admission. A combination of UA levels at admission and UA changes on serial assessment during hospitalization may be additional value in the risk stratification of AHF patients.

[Prognostic value of N-terminal B-type natriuretic peptide on all-cause mortality in heart failure patients with preserved ejection fraction].

Objective: To investigate the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) on all-cause mortality in heart failure patients with preserved ejection fraction (HFpEF) at real world scenarios. Methods: Patients who met the diagnostic criteria of HFpEF in the China National Heart Failure Registration Study (CN-HF) were divided into death and survival groups. The demographic data, physical examination, results of the first echocardiography, laboratory results at admission, complications, drug use and clinical outcomes were obtained from CN-HF. The univariate Cox proportional hazard model was used to screen the variates that might predict prognosis, and then the covariates with statistical significance were included in the multivariate Cox regression model to analyze the predictive value of baseline NT-proBNP on all-cause death. Spearman correlation analysis was used to evaluate the relationship between NT-proBNP and estimated glomerular filtration rate (eGFR), so as to further explore the predictive value of the interaction between renal dysfunction and NT-proBNP on death. Since NT-proBNP did not obey the binary normal distribution, it was expressed by the natural logarithm of NT-proBNP (LnNT-proBNP). Results: A total of 1 846 HFpEF patients were enrolled in this study, with an average age of 71.5 years, 1 017 males(55.1%), median NT-proBNP 860 ng/L, and median eGFR 73.9 ml·min-1·1.73m-2. After a median follow-up of 34 months, 213 (11.5%) patients died. Patients in the death group were older, with higher NYHA classification Ⅲ-Ⅳ ratio, longer hospital stay, higher serum potassium and NT-proBNP level, prevalence of complications of diabetes mellitus, arrhythmia and atrial fibrillation, use of angiotensin receptor antagonist(ARB), mineralocorticoid receptor antagonists (MRA), diuretic and digoxin was significantly higher in death group than in survival group. Body mass index (BMI), diastolic blood pressure, left ventricular ejection fraction (LVEF), hemoglobin, serum cholesterol(TC), serum triglycerides (TG) and eGFR, and use of angiotensin converting enzyme inhibitors (ACEI), statins and aspirin were lower in death group than in survival group. Univariate Cox regression analysis showed that NT-proBNP was a predictor of all-cause death in HFpEF patients (HR=2.522, 95%CI 2.040-3.119, P<0.001). Multivariate Cox regression analysis showed that the elevated NT-proBNP remains as the independent predictor of all-cause death in patients with HFpEF (HR=1.230, 95%CI 1.049-1.442, P=0.011) after adjusting for age, BMI, diastolic blood pressure, LVEF, hemoglobin, serum potassium, serum sodium, TC, serum high-density lipoprotein cholesterol (HDL-C), TG, eGFR, atrial fibrillation, as well as the treatment of ACEI/ARB, MRA, diuretics and digoxin. Spearman correlation analysis showed that LnNT-proBNP was negatively correlated with eGFR (r=-0.361, P<0.001), but there was no interaction between NT-proBNP and renal dysfunction in predicting death in HFpEF patients (P>0.05). Conclusion: The elevated level of NT-proBNP at admission is an independent predictor of all-cause mortality in HFpEF patients.

[Feasibility of screw placement on posterior occipital condyle assisted by occipital tangent angulation].

Objective: To investigate the practicability of occipital tangent angle in assisting posterior occipital condylar screw placement and to verify the safety and accuracy of self-made screw placement device for auxiliary screw. Methods: Occipito-cervical region specimens of 12 adult corpses were selected and scanned by thin-cut CT examination.The three-dimensional reconstruction of occipital and atlas was simulated for each specimen, and 3-matic software was used to measure the setting parameters, including occipital tangent angle, head obliquity, internal inclination angle, length of the screw and the distance from the inferior margin of hypoglossal canal to the screw axis.Using the self-designed occipital condylar screw placement device, combined with occipital tangent angle, internal inclination angle and insertion point, the posterior occipital condylar screw specimen was inserted with nails with assisting tool.The occipito-cervical region was reconstructed and scanned by thin-cut CT examination again after the operation to measuring the parameters of screw placement after actual screwing.The paired t test was used to compare the parameters of screw placement before and after operation. Results: Pre-operative three dimensional reconstruction of occipital condyle screw showed that the head obliquity was 5.3°±0.9°, the tangent angle was 14.9°±3.7°, the internal inclination angle was 28.1°±5.9°, and the length of screw insertion was (21.4±1.7) mm respectively; the distance from the inferior margin of hypoglossal canal to the screw axis was (4.74±0.36) mm.There was no significant difference in the parameters of analogue nailing between the left and right occipital condyles before the operation (t=-1.32, -0.48, 0.10, 0.23, 0.09, all P>0.05). The occipital condylar screw was safely implanted with screw placement device.The screw was located in the ideal nail insertion channel after operation by CT scan evaluation, without any injury to the hypoglossal canal, the atlanto-occipital articular surface and other structure.After the operation, the actual nailing parameters were measured: the head inclination angle was 5.2°±0.7°, the tangent angle was 15.1°±3.2°, the internal inclination angle was 28.2°±4.2°, the length of screw insertion was (21.5±1.7) mm, the distance from the inferior margin of hypoglossal canal to the screw axis was (4.54±0.29) mm.There was no significant difference between the left and right side in the actual screw placement parameters (t=-0.77, 0.82, 0.56, 0.22, 0.21, all P>0.05). It was found that there was no significant differences in the head obliquity, the occipital tangent angle, the internal inclination angle, length of screw entry, and the distance from the inferior margin of hypoglossal canal to the screw axis before and after the operation (t=0.56, -0.47, -0.18, -0.70, 1.89, all P>0.05). Conclusion: The occipital tangent angle can be measured directly in the process of posterior occipital condyle screw insertion to guide occipital condylar screw insertion, and the self-made occipital condylar screw placement device can effectively combine the three parameters: occipital tangent angle, head inclination angle and insertion point, which can improve the safety of posterior occipital condylar screw insertion.

[A retrospective analysis of clinical characteristics and outcomes of heart failure patients with different left ventricular ejection fractions].

Objective: To compare the clinical characteristics, and outcomes of patients with heart failure with different left ventricular ejection fractions (LVEF). Methods: A total of 1 182 hospitalized patients with heart failure (HF) were enrolled and retrospectively studied in the present study. The patients were stratified by LVEF as reduced (HFrEF, LVEF<40%, n=313), mid-range (HFmrEF, 40% ≤LVEF <50%, n=287) and preserved (HFpEF, LVEF≥50%, n=582) ejection fraction groups. Among the 1 182 cases, 941 of them (81.3%, 84.9%, and 84.0% inHFrEF, HFmrEF and HFpEF groups, respectively) were followed up for an median duration of 27.3 months. Results: (1) Among the study patients, 26.5% were in HFrEF, 24.3% in HFmrEF, and 49.2% in HFpEF groups. (2) Ischemic heart disease with HFmrEF was more frequent than that in patients with HFrEF. The average age, percentage of female subjects, systolic blood pressure, uric acid, N terminal B-type natriuretic peptide precursor (NT-proBNP), hemoglobin, and the incidence of hypertensive heart disease, anemia, atrial fibrillation in patients with HFmrEF were higher than those in patients with HFrEF, but lower than those in patients with HFpEF (all P<0.01). (3) The all-cause cumulative mortality was 10.8% at 1 year, 20.6% at 2 years and 35.9% at 5 years. No difference was observed in the all-cause cumulative mortality at 1 year, 2 years, 5 years among the three groups (all P>0.05). Conclusions: The HFmrEF patients, as a new and distinct group, were with many intermediate characteristics compared with HFrEF and HFpEF subjects. However, the all-cause mortality was not significantly different among HF patients with different LVEF.

Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

Stability and chaotification of vibration isolation floating raft systems with time-delayed feedback control.

This paper presents a systematic study on the stability of a two-dimensional vibration isolation floating raft system with a time-delayed feedback control. Based on the generalized Sturm criterion, the critical control gain for the delay-independent stability region and critical time delays for the stability switches are derived. The critical conditions can provide a theoretical guidance of chaotification design for line spectra reduction. Numerical simulations verify the correctness of the approach. Bifurcation analyses reveal that chaotification is more likely to occur in unstable region defined by these critical conditions, and the stiffness of the floating raft and mass ratio are the sensitive parameters to reduce critical control gain.

Androgen receptor inhibition alleviated inflammation in experimental autoimmune myocarditis by increasing autophagy in macrophages.

OBJECTIVE: Experimental autoimmune myocarditis (EAM) is characterized by pronounced macrophage infiltration, cardiac necrosis, and cardiac fibrosis. Our previous studies have demonstrated that suppressed androgen receptor (AR) enables anti-inflammation to promote tissue repair by decreasing M1 macrophages and increasing M2 macrophages in an EAM model. Given that autophagy mediates inflammatory response in macrophages, we investigated whether AR inhibition executes its protective role in inflammation through the autophagy pathway in EAM. MATERIALS AND METHODS: To determine whether AR inhibition can perform its anti-inflammatory effects by upregulating autophagy, we pre-treated mice with 3-methyl adenine (3-MA), a pharmacological inhibitor of autophagy. Immunofluorescence assay and Western blot were used to detect autophagy levels and autophagy activity in five different groups. Immunofluorescence marked F4/80 and LC3 to illustrate the autophagy level in macrophages. TUNEL assays were used to detect the apoptosis level in heart tissue of five different groups. RESULTS: We demonstrated that AR inhibition resolves injury with sustained inhibition of inflammatory cytokines associated with enhanced autophagy, especially in macrophages. Increased LC3II/I expression corroborated complete autolysosome formation detected by electron microscopy and correlated with degradation of SQSTM1/p62 in the AR inhibition group by Western blot. These effects could be reversed within 3-MA, a pharmacological inhibitor of autophagy. Specifically, pharmacological inhibition of autophagy increased apoptosis and inflammation, which could be attenuated by AR inhibition. CONCLUSIONS: AR inhibition alleviates the inflammatory response and tissue apoptosis by enhancing autophagy, especially in macrophages.

Complete nucleotide sequence and taxonomy of Sugarcane streak mosaic virus, member of a novel genus in the family Potyviridae.

The complete genomic sequence of a Pakistani isolate of Sugarcane streak mosaic virus (SCSMV-PAK) is determined to be 9782 nucleotides in length, excluding the 3' poly(A) tail, and it comprises a large open reading frame encoding a polyprotein of 3130 amino acid residues. The deduced polyprotein is likely to be cleaved at nine putative protease sites by three viral proteases to ten mature proteins. Conserved motifs of orthologous proteins of other potyviruses are identified in corresponding positions of SCSMV-PAK. The genomic organization is virtually identical to the genera Ipomovirus, Potyvirus, Rymovirus, and Tritimovirus in the family Potyviridae. Sequence analyses indicate that the SCSMV-PAK genomic sequence is different from those of Sugarcane mosaic virus and Sorghum mosaic virus, two viruses with very similar symptoms and host range to SCSMV-PAK. SCSMV-PAK shares 52.7% identity with Triticum mosaic virus (TriMV) and 26.4-31.5% identities with species of the existing genera and unassigned viruses in the Potyviridae at the polyprotein sequence level. Phylogenetic analyses of the polyprotein and deduced mature protein amino acid sequences reveal that SCSMV, together with TriMV, forms a distinct group in the family at the genus level. Therefore, SCSMV should represent a new genus, Susmovirus, in the Potyviridae.

Influences of low level of dietary calcium on bone characters in laying hens.

Cage layer fatigue (CLF), which is commonly caused by calcium deficiency in the feed, leads to loss of structural bone and increase of bone fragility. In order to investigate the influence of low-calcium diets on bone quality and strength, histopathology, and egg quality, 72 laying hens were randomly allocated to 2 groups at 22 wk of age and received low calcium and control calcium until 34 wk, respectively. Egg production, feed consumption, BW, and egg quality were measured throughout. Bone mineral density, bone biomechanical properties, and histomorphology of femurs and tibias were assessed after birds were sacrificed in 26, 30, and 34 wk. The results showed that low-calcium (1.5%) diets decreased BW, feed consumption, and egg production. The broken eggs rate increased, and the eggshell strength and thickness were lower in treated birds than those in control birds at 30 wk and 34 wk. Femoral and tibial bone index and bone mineral density were lower, cortical thicknesses were thinner, and bone length were shorter over time when birds are in a low-calcium diet than those in control birds. In biomechanical properties, the values of stiffness, Young's modulus, and breaking strength were lower in both femurs and tibias in low-calcium hens at 30 wk and 34 wk than those in bones of control hens. In histomorphology of bone, the cortex turned thinner and there were more cavities in cortex and cancellous bone; the trabecular bone network was fewer, thinner, less cohesive, and generally fragmented; and trabeculae were less well-connected in low-calcium birds. Some cell nuclei in cancellous bone disappeared, and vacuolation was observed in bone cells. There appeared osteoid in cortex bone and cancellous bone in tibias. It was concluded that low-calcium diets could facilitate the development of osteoporosis characterized by an increase of osteoid and loss of structural bone and decrease the values of bone quality and strength, accompanied with a decrease in egg production and egg qualities, which may elucidate the developing mechanism of CLF.

[Screening and bioinformatic analysis of trehalase in Thelazia callipaeda].

OBJECTIVE: To characterize the trehalase gene in Thelazia callipaeda through screening the annotated data of the T. callipaeda genome, and to investigate the biological characteristics of the trehalase gene-coding protein. METHODS: The trehalase gene was screened from the T. callipaeda genome and subjected to validation by using a PCR assay. The structural features of the coding protein were analyzed with bioinformatics tools, including hydrophobicity, transmembrane region, signal peptides, conserved domains, as well as the secondary and tertiary structures and the antigen epitope. Homology analysis of the amino acid sequences was performed, and the phylogenetic tree was built by the MEGA X software. In addition, the protein-protein interaction network was deduced from the STRING database. RESULTS: The sequence of the trehalase gene with the complete CDS region was obtained from T. callipaeda genome, which had a length of 1 638 bp and encoded 545 amino acids. The encoded protein was predicted to have a molecular weight of 63 478.48 ku and be a secretory protein. The 5' domain of the encoded protein contained a signal peptide without transmembrane regions, and was predicted to contain 7 antigen epitopes. Based on the protein-protein interaction network of nematodes in the STRING database, the protein-protein interaction network of the trehalase gene of T. callipaeda was deduced, and 27 interactions covering 10 genes were identified. CONCLUSIONS: A trehalase gene is successfully identified in T. callipaeda genome and its coding protein receives a bioinformatics analysis, which provides insights into the research on the biological functions of the protein and the screening of vaccine candidates for thelaziasis callipaeda.

[Association between puberty with thyroid morphology and function in women].

Objective: To explore the effects of different puberty development stages on thyroid morphology and function in women. Methods: From October to November 2017, a multi-stage cluster sampling method was used to select one junior high school in Minhang district of Shanghai, Haimen city of Jiangsu province, Yuhuan city of Zhejiang province and Deqing county of Zhejiang province respectively. A total of 491 girls in the first grade in 4 schools were included in the study. The subjects were examined with thyroid B-ultrasound and physical examination, and their morning random urine samples and fasting blood samples were collected to detect urinary iodine and thyroid function indexes. Puberty Development Self-rating Scale (PDS) was used to evaluate the stages of puberty; multiple linear regression models and logistic regression models were used to investigate the effects of different puberty stages on thyroid morphology and function. Results: There were differences in thyroid status among women at different stages of puberty. Thyroid volume, the rate of nodules and the level of FT4 were lowest in prepubertal period, followed by pubertal period and postpubertal period (P<0.05). TT3 and FT3 levels were highest in prepubertal period, followed by pubertal period and postpubertal period (P<0.001), and there was an opposite trend on the abnormal rate. TSH and TT4 levels were not affected by the stage of puberty (P>0.05). Multiple linear regression analysis and multivariate logistic regression analysis showed consistent results. There was a negative correlation between puberty development and TT3 and FT3 levels. For each 1 point increase in PDS, TT3 and FT3 levels decreased by 0.067 nmol/L and 0.170 nmol/L in Model 1, respectively, and decreased by 0.065 nmol/L and 0.162 nmol/L in Model 2, respectively. Compared with the prepubertal period, the TT3 and FT3 levels were lower in postpubertal period (Model 1: OR=0.337, 95%CI: 0.173-0.658; OR=0.283, 95%CI: 0.144-0.557; Model 2: OR=0.306, 95%CI: 0.155-0.605; OR=0.263, 95%CI: 0.132-0.524). Conclusions: The process of puberty is related to the thyroid status in women. The better matured during the puberty, the larger volume the thyroid was, more likely the thyroid nodules appeared, and the levels of TT3 and FT3 was much lower.

A methodology to model causal relationships on offshore safety assessment focusing on human and organizational factors.

INTRODUCTION: Focusing on people and organizations, this paper aims to contribute to offshore safety assessment by proposing a methodology to model causal relationships. METHOD: The methodology is proposed in a general sense that it will be capable of accommodating modeling of multiple risk factors considered in offshore operations and will have the ability to deal with different types of data that may come from different resources. Reason's "Swiss cheese" model is used to form a generic offshore safety assessment framework, and Bayesian Network (BN) is tailored to fit into the framework to construct a causal relationship model. The proposed framework uses a five-level-structure model to address latent failures within the causal sequence of events. The five levels include Root causes level, Trigger events level, Incidents level, Accidents level, and Consequences level. To analyze and model a specified offshore installation safety, a BN model was established following the guideline of the proposed five-level framework. A range of events was specified, and the related prior and conditional probabilities regarding the BN model were assigned based on the inherent characteristics of each event. RESULTS: This paper shows that Reason's "Swiss cheese" model and BN can be jointly used in offshore safety assessment. On the one hand, the five-level conceptual model is enhanced by BNs that are capable of providing graphical demonstration of inter-relationships as well as calculating numerical values of occurrence likelihood for each failure event. Bayesian inference mechanism also makes it possible to monitor how a safety situation changes when information flow travel forwards and backwards within the networks. On the other hand, BN modeling relies heavily on experts' personal experiences and is therefore highly domain specific. IMPACT ON INDUSTRY: "Swiss cheese" model is such a theoretic framework that it is based on solid behavioral theory and therefore can be used to provide industry with a roadmap for BN modeling and implications. A case study of the collision risk between a Floating Production, Storage and Offloading (FPSO) unit and authorized vessels caused by human and organizational factors (HOFs) during operations is used to illustrate an industrial application of the proposed methodology.

[Identification and drug susceptibility testing of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis].

Objective: To understand the etiological characteristics and drug susceptibility of Mycobacterium thermoresistibile and Mycobacterium elephantis isolated from a cow with mastitis and provide evidence for the prevention and control of infectious mastitis in cows. Methods: The milk sample was collected from a cow with mastitis, which was pretreated with 4% NaOH and inoculated with L-J medium for Mycobacterium isolation. The positive cultures were initially identified by acid-fast staining and multi-loci PCR, then Mycobacterium species was identified by the multiple loci sequence analysis (MLSA) with 16S rRNA, hsp65, ITS and SodA genes. The drug sensitivity of the isolates to 27 antibiotics was tested by alamar blue assay. Results: Two anti-acid stain positive strains were isolated from the milk of a cow with mastitis, which were identified as non-tuberculosis mycobacterium by multi-loci PCR, and multi-loci nucleic acid sequence analysis indicated that one strain was Mycobacterium thermoresistibile and another one was Mycobacterium elephantis. The results of the drug susceptibility test showed that the two strains were resistant to most antibiotics, including rifampicin and isoniazid, but they were sensitive to amikacin, moxifloxacin, levofloxacin, ethambutol, streptomycin, tobramycin, ciprofloxacin and linezolid. Conclusions:Mycobacterium thermoresistibile and Mycobacterium elephantis were isolated in a cow with mastitis and the drug susceptibility spectrum of the pathogens were unique. The results of the study can be used as reference for the prevention and control the infection in cows.

Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.

Upregulation of aquaporin-2 water channel expression in chronic heart failure rat.

Aquaporin-2 (AQP2) mediates vasopressin-regulated collecting duct water permeability. Chronic heart failure (CHF) is characterized by abnormal renal water retention. We hypothetized that upregulation of aquaporin-2 water channel could account for the water retention in CHF. Male rats underwent either a left coronary artery ligation, a model of CHF, or were sham operated. 31-33 d after surgery, mean arterial pressure (MAP) and cardiac output were measured in conscious animals, and the animals were killed 24 h later. Cardiac output (CO) and plasma osmolality were significantly decreased and plasma vasopressin increased in the CHF as compared to the sham-operated rats. Both mRNA and protein AQP2 were significantly increased in the kidneys of the CHF rats. The effect of oral administration of a nonpeptide V2 vasopressin receptor antagonist, OPC 31260, was therefore investigated. OPC 31260 induced a significant increase in diuresis, decrease in urinary osmolality, and rise in plasma osmolality in the OPC 31260-treated CHF rats as compared to untreated CHF rats. The mRNA and protein AQP2 were significantly diminished in both cortex and inner medulla of the treated CHF rats. In conclusion, an early upregulation of AQP2 is present in CHF rats and this upregulation is inhibited by the administration of a V2 receptor antagonist. The results indicate a major role for vasopressin in the upregulation of AQP2 water channels and water retention in experimental CHF in the rat.

Upregulation of aquaporin 2 water channel expression in pregnant rats.

Water retention is characteristic of pregnancy but the mechanism(s) of the altered water metabolism has yet to be elucidated. The collecting duct water channel, aquaporin 2 (AQP2), plays a pivotal role in the renal water regulation, and we hypothesized that AQP2 expression could be modified during pregnancy. Sprague-Dawley female rats were studied on days 7 (P7), 14 (P14), and 20 (P20) of pregnancy, and expression of AQP2 in papillae was examined. Nonpregnant (NP) littermates were used as controls. Plasma osmolalities were significantly lower in pregnant rats by day 7 of gestation (P7 283.8+/-1.82, P14 284.3+/-1.64, P < 0.001, P20 282. 4+/-1.32, P < 0.0001, vs. NP 291.8+/-1.06 mosmol/kgH2O). However, plasma vasopressin concentrations in pregnant rats were not significantly different than in nonpregnant rats (NP 1.03+/-0.14, P7 1.11+/-0.21, P14 1.15+/-0.21, P20 1.36+/-0.24 pg/ml, NS). The mRNA of AQP2 was increased early during pregnancy: AQP2/beta actin: P7 196+/-17.9, P14 200+/-6.8, and P20 208+/-15.5%, P < 0.005 vs. NP (100+/-11.1%). AQP2 protein was also increased during pregnancy: AQP2 protein: P7 269+/-10.0, P14 251+/-12.0, P < 0.0001, and P20 250+/-13.6%, P < 0.001 vs. NP (100+/-12.5%). The effect of V2 vasopressin receptor antagonist, OPC-31260, was then investigated. AQP2 mRNA was suppressed significantly by OPC-31260 administration to P14 rats (AQP2/beta actin: P14 with OPC-31260 39.6+/-1.7%, P < 0.001 vs. P14 with vehicle) and was decreased to the same level of expression as NP rats receiving OPC-31260. Similar findings were found with the analysis of AQP2 protein. The decreased plasma osmolality of P14 rats was not modified by OPC-31260. The results of the study indicate that upregulation of AQP2 contributes to the water retention in pregnancy through a V2 receptor-mediated effect. In addition to vasopressin, other factors may be involved in this upregulation.