OBJECTIVERecent studies have shown that cytokines TNF-alpha and IL-6 play important roles in myocardial injury or dysfunction. Transcription nuclear factor (NF-kappa B) have been implicated in the regulation of a variety of cytokines in response to cellular defense. The authors observed the activity of NF-kappa B and cytokines TNF-alpha, IL-6 mRNA expression in myocardium to further investigate the mechanism of myocardial injury caused by infectious pneumonia. The therapeutic effect of exogenous adenosine was also studied by observing the influence on NF-kappa B and cytokines.

METHODSThirty rats were divided into three experimental groups at random, each group had 10 rats. The model of pneumonia was induced by the injection of Staphylococcus aureus into the trachea of rats. Adenosine-treated rats were given daily slow intravenous injection of adenosine at a dose of 150 microg/kg.min for 3 days from the second day. All rats were killed on the fifth day. Myocardial tissues were preserved in liquid nitrogen for examination. Pathological examination of myocardium was done and TNF-alpha and IL-6 mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). NF-kappa B activity was measured by electrophoretic mobility shift assay (EMSA).

RESULTS(1) The myocardium in pneumonia group showed significant pathological lesion when compared with control group (P < 0.01). The pathological lesion of myocardium in adenosine-treated group significantly decreased when compared to pneumonia group (P < 0.05). (2) Significant increase of TNF-alpha and IL-6 mRNA expression was observed in myocardium of pneumonic rats when compared with control group (2.27 +/- 0.27 vs. 1.05 +/- 0.16; 1.89 +/- 0.31 vs. 1.12 +/- 0.25: P < 0.01, respectively). NF-kappa B activity of myocardium in pneumonia group was significantly higher than that in control group (13,033 +/- 1286 vs. 383 +/- 15: P < 0.01). (3) TNF-alpha and IL-6 mRNA expression was significantly decreased in adenosine-treated group when compared with pneumonia group (1.25 +/- 0.18 vs. 2.27; 1.31 +/- 0.25 vs. 1.89 +/- 0.31, P < 0.01, respectively). Comparing to that in pneumonia group, NF-kappa B activity of myocardium in adenosine-treated group was significantly decreased (4 487 +/- 562 vs. 13033 +/- 1286, P < 0.01), but it was still significantly higher than that in control group (4487 +/- 562 vs.383 +/- 15, P < 0.01).

CONCLUSIONSIncreased activity of NF-kappa B and subsequent upregulation of TNF-alpha and IL-6 mRNA expression probably play a pivotal role in the mechanism of myocardial injury in rats with pneumonia. Exogenous adenosine can inhibit inflammatory change by lowering NF-kappa B activity and subsequent down-regulation of TNF-alpha and IL-6 expression. Our findings provide novel therapeutic evidence of adenosine in myocardial injury induced by pneumonia in clinic.

Adenosine ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Electrophoretic Mobility Shift Assay ; Female ; Gene Expression ; drug effects ; Interleukin-6 ; genetics ; metabolism ; Male ; Myocardium ; metabolism ; NF-kappa B ; genetics ; metabolism ; Pneumonia, Staphylococcal ; drug therapy ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVEWe investigate the magnitudes of waveform changes of arterial blood gas (ABG) in patients with heart failure.

METHODSFive patients with heart failure were selected, continuous collecting radial artery blood and measured PaO2, PaCO2, pHa and Sao2. We selected two typical breaths cycles of waveform changes of ABG from each patient for data analysis. Comparison of the adjacent highest and lowest values to verify the presence of a periodic waveform changes of ABG, and in addition, we used t test to analysis the range of waveform changes of ABG in patients with heart failure and patients with normal cardiac function and compared whether the difference between them.

RESULTSThe 5 patients (2 surgical and 3 ICU) with heart failure, were 4 male and 1 female, (69 ± 7)year, (169 ± 10) cm, (75 ± 19)kg, LVEF = (38 ± 3)%. The heart beat numbers for full blood into the blood sampling pipe were 17 ± 2, and all covered more than 2 breath cycles. There were significant changes of PaO2, PaCO2, [H+]a and SaO2 (P < 0.05). The magnitudes of changing PaO2, PaCO2, [H+]a and Sao2 were (7.94 ± 2.02)mmHg, (1.18 ± 0.56)mmHg, (0.54 ± 0.17)nmol/L and (0.21 ± 0.07)%, and they were (6.1 ± 1.5)%, (3.2 ± 1.5)%, (1.5 ± 0.5)% and (0.2 ± 0.1)% from their mean respectively. Even these magnitudes fo all ABG parameters were trendily lower than those of patients with normal cardiac function, but only PaO2 and [H+]a were significant (P < 0.05).

CONCLUSIONUsing this simple continuous beat-by-beat arterial blood sampling method, we obtained a clear evidence of periodic waveform of ABG parameters following by breath cycle in patients with heart failure, but the magnitude trendily be decreased.

Aged ; Blood Gas Analysis ; Cardiovascular Diseases ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; methods

Objective To assess the prevalence rates of intra-and extraeranial large-artery stenosis in the rural community population and its related risk to the development of stroke.Methods The study subjects included 1337 residents in the rural community of Beijing.Transcranial Doppler Was carried our to examine the relation between intra-and extracranial large-artery stenosis and subsequent cerebrovascular events, with a meall follow-up period of 16.7 months.Results The incidence densities of cerebral infarction and cerebral hemorrhage in persons without cerebral large-artery stenosis were 410.6 and 351.9/100-thousand person-years,respectively.In the group wlth large-artery stenosis,the incidence density of cerebral infarction was 3303.7/100-thousand person-years.Data from The Fisher's Exact test showed a significant difference in the two groups (P=0.004).Cerebral large-artery stenosis(OR=6.593,95%CI:1.712-25.390)and smoking (OR=8.437,95% CI:2.327-30.598)appeared to be independent risk factors to cerebral infarction.Conclusion Cerebral large-artery stenosis and smoking were independent risk factors to cerebral infarction.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Humans ; Melphalan ; Multiple Myeloma

Adolescent ; Androgen-Insensitivity Syndrome/genetics* ; Cytosine ; Female ; Guanine ; Humans ; Male ; Mutation ; RNA Splice Sites/genetics* ; Receptors, Androgen/genetics*

Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel (c.2112 C>G[p.S704R], c.2290T>A[p.Y764N], c.2626C>T[p.Q876X], c.933dupC[p.K313Qfs*28], and c.1067delC[p.A356Efs*123]); the other five were previously reported (c.1789G>A[p.A597T], c.2566C>T[p.R856C], c.2668G>A[p.V890M], c.2679C>T[p.P893L], and c.1605C>G[p.Y535X]). Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% (3/10) of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.
Adolescent ; Adult ; Androgen-Insensitivity Syndrome/genetics* ; Child ; Child, Preschool ; DNA Mutational Analysis ; Genetic Association Studies ; Humans ; Male ; Mutation, Missense ; Phenotype ; Receptors, Androgen/genetics* ; Symptom Assessment ; Young Adult

Chronic kidney disease (CKD) is a progressive disease with many complications (eg, cardiovascular disease and acidosis and anemia) and high morbidity and mortality occurs in the population. There is no cure for this disease, current treatments including renin-angiotensin-aldosterone pathway inhibitors and sodium-glucose co-transporter 2 inhibitors can only delay the progression to end-stage renal disease. With the identification of more key factors and mechanisms in CKD development, new potential therapeutic approaches for CKD can be developed. This review summarizes the mainstays of therapy and strategies for CKD and related comorbidities to support the development of novel treatments.