Endogenous ouabain (EO) is a recently found hormone that may be secreted from adrenal cortex. As an endogenous mammalian analogue of cardiac glycosides and an inhibitor of the sodium pump, it regulates the body fluid balance, urine sodium extraction and vasoconstrictive tone, and thus plays an important role in the pathogenesis of hypertension and some other cardiovascular disorders. This articke reviews its biological features, receptor and antibody, detection, effects on diseases and relationship with endothelial cells.
Adrenal Cortex ; metabolism ; Animals ; Antibodies ; therapeutic use ; Humans ; Hypertension ; etiology ; Nephrotic Syndrome ; etiology ; Ouabain ; immunology ; pharmacology ; Sodium-Potassium-Exchanging ATPase ; immunology ; physiology

OBJECTIVETo investigate the changes in rat cardiac function and myocardium ultrastructure in response to ouabain treatment.

METHODSTwenty-four male SD rats were randomized into two equal groups to receive daily intraperitoneal injection of ouabain or saline for 4 consecutive weeks, and their systolic blood pressure (SBP) was recorded weekly. After 4 weeks of injection, echocardiography was performed and the hemodynamic parameters were measured by invasive cardiac catheterization, and the changes in myocardium ultrastructure observed using transmission electron microscopy.

RESULTSAfter 4 weeks of ouabain injection, no significant changes in the mean SBP occurred in comparison with the saline group, but echocardiographic examination showed significant increases in the left ventricular end-diastolic and end-systolic diameters, septum thickness, posterior wall thickness, left ventricular mass and isovolumetric relaxation time but significantly lowered E/A ratio, ejection fraction and fractional shortening after ouabain treatment (P<0.05). Invasive monitoring revealed significant attenuation of the left ventricular developed pressure, rate of pressure development (+dp/dt) and rate of pressure decay (-dp/dt), and increment of the left ventricular end diastolic pressure. Myofibrillar fragmentation, swelling of the cardiac myocytes, absence of the Z line, increases of the mitochondria and collagen fibers were found in ouabain group by transmission electron microscopy.

CONCLUSIONOuabain can induce left ventricular enlargement, cardiac wall thickening, myocardial ultrastructural alterations, systolic and diastolic dysfunction in rats before blood pressure elevation is detected, indicating that ouabain can directly cause cardiac damage in rats.

Animals ; Echocardiography ; Heart ; drug effects ; physiopathology ; Male ; Microscopy, Electron, Transmission ; Myocardium ; pathology ; ultrastructure ; Ouabain ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the role of renal sympathetic nerves in renal sodium transport in ouabain-hypertensive rats (OHR).

METHODSSixteen male SD rats with sham renal denervation (Sham-RDNX) and 16 with renal denervation (RDNX) were randomly into normal control group and ouabain group to receive intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 µg/kg) once a day, respectively. Systolic blood pressure (SBP), heart rate and body weight were recorded weekly. Food consumption of the rats was determined twice a week. After a 4-week treatment, blood and 24 h urine samples were collected to measure the serum and urinary concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the postproximal tubules (FDRNa) were calculated. Plasma renin activity was determined by radioimmunoassay. Norepinephrine was extracted from the renal tissue and assayed for norepinephrine content by HPLC.

RESULTSThe body weight, food intake and heart rate showed no significant difference among the 4 groups (P > 0.05). After 4 weeks, the SBP of control RDNX group (CDNX) was significantly lower than that of the control Sham-DNX group (Csham)(P < 0.05); the SBP of ouabain RDNX group (ODNX) was also significantly lower than that of ouabain Sham-DNX group (Osham) (P < 0.05); RNDX lowered SBP by about 10 mmHg in both ouabain groups and control groups. The SBP was significantly higher in Osham and ODNX groups than in the corresponding control groups (P < 0.01), also significantly higher in ODNX group than in Csham group (P < 0.01). Ccr showed no significant difference among the 4 groups(P > 0.05). FENa, FELi and FDRNa were significantly lower in ouabain groups than in the corresponding control groups (P < 0.05, P < 0.01, P < 0.05), but FENa, FELi and FDRNa of ODNX group were similar with those of Osham group (P > 0.05); FENa , FELi and FDRNa were similar between CDNX and Csham groups (P > 0.05). The plasma renin activity was comparable between the 4 groups (P > 0.05). Renal norepinephrine level was markedly reduced in RDNX group compared with that in Sham-RDNX group in both ouabain and control groups (P < 0.01).

CONCLUSIONThe increase of proximal tubule sodium reabsorption in OHR is not dependent on the renal sympathetic nerve.

Animals ; Hypertension ; chemically induced ; metabolism ; Kidney ; innervation ; Male ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; metabolism ; Sodium Channels ; metabolism ; Sympathetic Nervous System ; physiology

OBJECTIVETo investigate the changes in renal sodium transport during development of hypertension in ouabain-hypertensive rats (OHR) and further elucidate the role of ouabain in the pathogenesis of hypertension.

METHODSEighty male SD rats weighing 80-100 g were randomized equally into normal control and ouabain groups and treated with intraperitoneal injection of normal saline (1 ml/kg) and ouabain (27.8 microg/kg) once daily, respectively. Systolic blood pressure (SBP) and body weight of the rats were recorded weekly. One week before sacrifice scheduled at weeks 2, 4, 6 and 8, respectively, the rats were individually housed in metabolic cages to determine food consumption twice. Blood and 24-hour urine samples were collected to measure serum and urine concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate (Ccr), fractional excretions of sodium (FENa), fractional excretions of lithium (FELi) and fractional reabsorption of sodium in the distal tubules (FDRNa) were calculated.

RESULTSThe body weight and food intake between ouabain groups and control groups were comparable during the experiment (P>0.05). Blood pressure was also comparable in the two groups after 2 weeks (P>0.05). At week 4, however, blood pressure of ouabain group was significantly higher than that of the control group (P<0.001) and increased in a dose-dependent manner. The SBP in ouabain group appeared to reach a plateau at week 7. Ccr and plasma sodium (PNa) were similar in the 2 groups during the experiment (P>0.05). FELi was significantly lower at weeks 2, 4 and 6 in ouabain group than in the control group (P<0.01), and FELi decrement in ouabain group was accompanied by reduced sodium excretion. FENa was significantly lower at week 4 in ouabain group than in the control group (P<0.05), but this difference was not significant in weeks 2 and 6 (P>0.05). At weeks 2, 4 and 6, ouabain group showed significantly lower FDRNa than the control group (P<0.05), suggesting the compensation of the distal nephron segments. After 8 weeks, FENa, FELi and FDRNa were similar between the two groups (P>0.05).

CONCLUSIONSOuabain can increase renal proximal tubule reabsorption of sodium and consequently decrease renal sodium excretion in OHR, which can contribute to alteration of the pressure-natriuresis relationship in OHR, and play an important role in the development and maintenance of hypertension of OHR.

Animals ; Blood Pressure ; Creatinine ; blood ; Hypertension ; chemically induced ; metabolism ; physiopathology ; Ion Transport ; Kidney Tubules, Proximal ; metabolism ; Male ; Ouabain ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sodium ; blood ; metabolism

The aim of this study was to establish a diagnostic method for ABO genotyping and to investigate the distribution of ABO genotype in Beijing Han population so as to understand the distribution characteristics and regularity of ABO genotype. An ABO genotyping method was established by using multiplex-PCR-RFLP and PCR-SSP techniques, and the ABO allele frequency in Beijing Han population was investigated. The results showed that A102, O1 and B allele were more common genes in Beijing Han individuals. And A102 allele was predominant in the phenotype A group in this population. Three O2 alleles were found and no A201 allele was found while gene frequency investigation was performed. No A101A101, A101O2, A102O2, BO2 and O2O2 in this population were discovered. It is concluded that the primary regularity of ABO allele distribution in Beijing Han population is found through this study. It provides basic reference for further study of ABO types.
ABO Blood-Group System ; genetics ; Adult ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic ; Young Adult

OBJECTIVETo understand the epidemiological characteristics of essential hypertension in the northern and western areas of China.

METHODSA community-based sampling survey.

RESULTSRates of awareness, treatment and control were 78.6%, 59.7% and 5.9%, respectively. About half of the diagnosed and treated patients took antihypertensive medicine irregularly before the survey was carried out.

CONCLUSIONIt is necessary to carry out education, prevention and control on hypertension and to establish a series of standards for the management and treatment on cases of hypertension.

Adult ; Age Factors ; Aged ; Blood Pressure ; China ; epidemiology ; Drug Administration Schedule ; Female ; Health Surveys ; Humans ; Hypertension ; epidemiology ; prevention & control ; therapy ; Male ; Middle Aged ; Risk Factors ; Social Class

Limitations of polyacrylamide gel or agarose gel electrophoretic methods in genotyping research affect the interpreting of detection results. In order to develop a simple and reliable method for appraising results of ABO genotyping detection, the microfluidic chip analysis system was established by using microfluidic chip to replace the gel electrophoresis and combining with multiplex-PCR-RFLP technique. 150 blood samples were tested by this microfluidic chip analysis system with multiplex-PCR-RFLP technique to evaluate its stability and accuracy. The results showed that all the testing results were consistent with serologic ABO genotyping results and 1 blood sample with decrease of B antigen caused by CML was identified. In conclusion, the established microfluidic chip analysis system is stable and reliable technique. Application of this technique enables the ABO genotyping results to be more objective and accurate.
ABO Blood-Group System ; genetics ; Blood Grouping and Crossmatching ; methods ; DNA Primers ; genetics ; Genotype ; Humans ; Microfluidic Analytical Techniques ; Microfluidics ; Oligonucleotide Array Sequence Analysis

OBJECTIVETo investigate the effect of endothelin and its receptors on ouabain-induced hypertension in rats.

METHODSMale Sprague-Dawley (SD) rats were treated with ouabain or saline for 6 weeks and their systolic blood pressure (SBP) were recorded weekly. At the end of 2, 4 and 6 weeks, respectively, the plasma and left ventricle endothelin contents were measured by radio-immunoassay, and real-time quantitative RT-PCR was employed to determine the mRNA level of endothelin type A receptor (ETAR) and type B receptor (ETBR) in the left ventricle, and the protein expressions of ETAR and ETBR were examined by immuno-histochemistry.

RESULTSAfter 4 weeks of intraperitoneal ouabain injection, the mean SBP in ouabain group increased till reaching a level significantly higher than that in the control group after 6 weeks (P<0.001). The plasma and left ventricle endothelin contents were significantly increased after 2 weeks of ouabain injection (P<0.01), and similarly, increased ETAR mRNA was observed. After 4 weeks of treatment, ETAR mRNA was increased continuously and the protein expression of ETAR upregulated in ouabain group as compared with the control group. The transcription and protein expression of ETBR were not altered by ouabain treatment.

CONCLUSIONBefore detectable blood pressure elevation occurs, endothelin concentration and ETAR can be already upregulated in ouabain-induced hypertensive rats, suggesting that endothelin might be involved in the cardiovascular effects of ouabain via an action on ETAR.

Animals ; Endothelins ; biosynthesis ; blood ; genetics ; Hypertension ; chemically induced ; genetics ; metabolism ; Immunohistochemistry ; Male ; Myocardium ; metabolism ; Ouabain ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A ; genetics ; metabolism ; Receptor, Endothelin B ; genetics ; metabolism ; Receptors, Endothelin ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo explore the association of the expressions of human leukocyte antigen (HLA)-DR4, peptidyl arginine deiminase type4(PAD4), and signal transducer and activator of transcription 4 (STAT4) in the peripheral blood with the disease activity in patients with rheumatoid arthritis (RA).

METHODSTwenty-four RA patients in active stage (DAS28 score>or=2.6) and 14 RA patients in remission stage (DAS28 score<2.6) were enrolled in this study, with 12 healthy volunteers as the control. The QuantiGene Plex method was used to measure the expression level of HLA-DR4, PAD4, and STAT4 mRNA, and the relationship between the expressions of these genes and the DAS28 score, levels of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and rheumatoid factor (RF) was analyzed.

RESULTSThe expressions of HLA-DR4, PAD4, and STAT4 were significantly higher in RA patients than in the healthy controls (P<0.05). The level of HLA-DR4 mRNA in the two RA groups showed no significant difference, but was significantly higher than that in the healthy controls. HLA-DR4 expression was not found to correlated to DAS28 score, anti-CCP antibody level or RF in the RA patients. The expressions of PAD4 and STAT4 were significantly different between the two RA groups (P<0.05). In the RA patients, PAD4 mRNA expression was positively correlated to DAS28 and anti-CCP antibody level (P<0.05), and STAT4 expression showed positive correlations to DAS28 and RF levels (P<0.05).

CONCLUSIONHLA-DR4, PAD4 and STAT4 are overexpressed in RA patients and may be involved in the pathogenesis of RA. The expressions of PAD4 and STAT4, but not HLA-DR4, are closely related to the disease activity of RA. Detection of peripheral blood PAD4 and STAT4 expressions can be helpful for evaluating the disease activity of RA.

Adult ; Arthritis, Rheumatoid ; blood ; Female ; HLA-DR4 Antigen ; blood ; genetics ; metabolism ; Humans ; Hydrolases ; blood ; genetics ; metabolism ; Male ; Middle Aged ; Protein-Arginine Deiminases ; RNA, Messenger ; genetics ; metabolism ; STAT4 Transcription Factor ; blood ; genetics ; metabolism

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.