Immunochromatography test for rapid diagnosis of Mycoplasma pneumoniae infection.

The sensitivity and specificity of a new rapid Mycoplasma pneumoniae antigen immunochromatography (IC) test, DK-MP-001, were determined using particle agglutination (PA) antibody response and loop-mediated isothermal amplification (LAMP) gene detection as the gold standard. Of 165 patients, 59 were diagnosed with M. pneumoniae infection based on a ≥fourfold rise of serum PA antibody during the course of the illness. Of the first visit swabs, 60 were positive for M. pneumoniae on LAMP, and 49 were positive for M. pneumoniae antigen on IC test. Compared with PA antibody and LAMP, the sensitivity/specificity of the IC test were 81.4% (48/59) and 99.1% (105/106); and 81.7% (49/60) and 100% (105/105), respectively. IC test detected antigen in pharyngeal swabs more sensitively than in nasal swabs for the same subjects (P < 0.05). The IC test performs well enough to be used with pharyngeal swabs at the first examination.

Protection from sepsis-induced acute renal failure by adenoviral-mediated gene transfer of beta2-adrenoceptor.

BACKGROUND: Sepsis is a common cause of acute renal failure (ARF) and results in a high mortality rate. The objective of the present study was to evaluate adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) as a possible therapy for subjects at high risk for developing sepsis-induced ARF. METHODS: An endotoxaemic rat model of ARF was induced by renal artery occlusion plus subcutaneous injections of Escherichia coli in 4-week-old Wistar rats. A subset of rats was given intraperitoneal injection of the adeno-beta(2)-AR gene. RESULTS: Sepsis produced a depression in glomerular filtration rate and in the renal beta(2)-AR signalling system, which were both reversed by delivery of the beta(2)-AR gene. While delivery of the adeno-beta(2)-AR gene had no effect on recovery of cytokines and C-reactive protein in the systemic circulation, it did significantly depress (P < 0.01) the expression of the renal cannabinoid-1 (CB-1) receptor, CD14, toll-like receptor 4 (TLR4) and tumour necrosis factor (TNF)-alpha protein. Gene delivery also increased nitric oxide (NO) and decreased angiotensin II (Ang II). Finally, transfer of the beta(2)-AR gene also improved the survival of the rats exposed to sepsis-induced ARF. CONCLUSIONS: A renal-specific over-expression of beta(2)-AR, resulting from gene delivery, appeared to modulate renal dysfunction and inflammation following sepsis by altering cAMP-PKA, CB-1 and CD14-TLR4-TNF-alpha pathways. In addition, gene delivery and activation of beta(2)-AR produced modulation of systemic NO and Ang II, which further protected against renal dysfunction. Administration of the Adeno-beta(2)-AR gene has potential as a therapeutic agent against ARF following the onset of sepsis.

Renal beta2-adrenoceptor blockade worsens the outcome of an induced Escherichia coli renal infection.

BACKGROUND: Renal infections elevate the risk of sepsis and are important causes of septic shock and multiple organ failure. The objective of the present study was to test the hypothesis that renal beta(2)-adrenoceptor (beta(2)-AR) blockade impairs the organ response to renal infection induced by Escherichia coli (E. coli) administration. METHODS: A rat model of renal infection was induced using an intraparenchymal injection of E. coli into the right kidney, either alone or in rats pre-treated with the beta(2)-AR antagonist, ICI 118,551 (3.14 microg/kg). RESULTS: The rat renal infection model significantly raised growth-related oncogene/keratinocyte-derived cytokine, granulocyte-macrophage colony-stimulating factor and cAMP levels in the right kidney and caused an elevation in serum cytokines and nitric oxide (NO), whereas creatinine clearance rate (Ccr) was maintained over the course of the infection. Conversely, treatment of the rat model with the beta(2)-AR antagonist resulted in a decrease of Ccr and serum NO, greater increases in serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6, associated with an elevation of the right renal TNF-alpha and cannabinoid-1 receptor, and a reduction of the right renal Gsalpha and cAMP levels. Moreover, the inhibition of beta(2)-AR activation impaired the clearance of endotoxins from the kidney and was associated with a raised mortality rate. CONCLUSIONS: The blockade of a renal beta(2)-AR signaling cascade aggravates inflammatory responses in the infected kidney, changes serum levels of cytokines, NO, and noradrenaline, and leads to renal dysfunction and a higher rate of mortality.

Factors influencing cardiovascular risk following termination of glucocorticoid therapy for nephrotic syndrome.

BACKGROUND: This study attempted to identify the cardiovascular risk factors associated with retention of excess weight following termination of glucocorticoid therapy in children with nephrotic syndrome. METHODS: We performed a retrospective study of 30 Japanese children (18 males, 12 females, aged 1-14 years) who had been treated with glucocorticoids for steroid-sensitive nephrotic syndrome and 32 control children (17 males, 15 females, aged 1-15 years). The subjects receiving glucocorticoid therapy were divided into a retention group (n = 14) or a reduction group (n = 16) on the basis of the presence or absence of a maintained body mass index (BMI) following glucocorticoid termination. BMI z-scores, age, gender, blood pressure, serum total cholesterol levels (T-cho), and the dose and duration of glucocorticoid exposure were evaluated in each group during the study period. RESULTS: The retention group had a significantly (P < 0.05) increased dose and duration of glucocorticoid exposure, and of T-cho at the time of last visit compared with the control or reduction group. Moreover, logistic regression analysis showed that the adjusted odds ratio for T-cho at the time of last visit in the retention group was significantly higher (P < 0.05) relative to the reduction group. CONCLUSION: Retention of excess weight during the period of remission from nephrotic syndrome following cessation of glucocorticoid therapy was related to the dose and duration of glucocorticoid exposure and was associated with hyperlipidemia, which might enhance cardiovascular risk.

Renal beta(2)-adrenoceptor modulates the lipopolysaccharide transport system in sepsis-induced acute renal failure.

The aim of this study was to define the contribution of renal beta(2)-adrenoceptor (beta(2)-AR) system to regulation of the lipopolysaccharide (LPS) transport system in the kidney of endotoxin-induced septic rats. Seven-week-old Wistar rats (n = 6/groups) pre-treated with the beta(2)-AR antagonist (ICI118,551: 3.14 microg/kg) or saline were injected with LPS (10 mg/kg i.p.) or saline, and then 24 hours later, renal function, beta(2)-AR signaling proteins, innate immune proteins, and cytokines were assayed. The injection of LPS depressed creatinine clearance rate (Ccr) associated with the reduction of renal Gsalpha and cAMP levels by a single dose of ICI118,551. On the other hand, renal CD14, toll-like receptor 4(TLR4), and tumour necrosis factor (TNF)-alpha protein expressions were significantly increased (P < 0.05) by the combination of LPS and ICI118,551. The reduction of Ccr by LPS plus ICI118,551 suggests a possibility that renal specific up-regulation of the CD14-TLR4-TNF-alpha signaling cascade by beta(2)-AR inhibition might be involved in sepsis-induced ARF.

Beta2-adrenoceptor activation inhibits Shiga toxin2-induced apoptosis of renal tubular epithelial cells.

Apoptosis is regulated by several pathways, such as caspases, mitogen activated protein kinase (MAPK) and cAMP/cAMP-dependent protein kinase A (PKA) cascade. This study investigated the effect of beta(2)-adrenoceptor activation on Shiga toxin (Stx)2-induced apoptosis in renal tubular cells and the contribution of these signalling pathways. Cultured human adenocarcinoma-derived tubular cells were exposed to Stx2 (64 pg/mL) for 2-24hr following the addition of the beta(2)-adrenoceptor agonist (terbutaline) to the incubation medium. Stx2-induced apoptosis and its amelioration by beta(2)-adrenoceptor activation was confirmed using DNA degradation assays and by flow cytometry for annexin V, mitochondrial membrane potential and caspase(-3 and -7) activity. Exposure of cells to Stx2 for 24hr increased the DNA fragmentation to 11.6+/-0.9%, compared to 3.3+/-0.2% in control cells (P<0.05) but was decreased to approximately 5-7% (P<0.05) in the presence of terbutaline. Furthermore, Stx2-stimulated apoptosis, detected by TUNEL, annexin V and mitochondrial potential, was inhibited by terbutaline (P<0.05) which was prevented by cAMP-PKA inhibitors and a beta(2)-adrenoceptor antagonist. However, inhibition of Stx2-mediated caspase activity by terbutaline was partially blocked by cAMP-PKA inhibitors. On the other hand, p38MAPK inhibition by terbutaline prevented Stx2-induced apoptosis and caspase activity through a cAMP-independent pathway via beta(2)-adrenoceptor. These data indicate that beta(2)-adrenoceptor activation can inhibit Stx2-induced apoptosis of the cells, which may be caused by a reduction in caspase activity through cAMP-PKA activation and the p38MAPK pathway.

Renal effects of beta2-adrenoceptor agonist and the clinical analysis in children.

The objectives of the present study were to define the contribution of beta2-adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether over-expression of renal beta2-ARs might be implicated in the pathogenesis of renal dysfunction in children as an adverse effect of beta2-AR activation. The renal functional responses to the systemic injection of the beta2-AR agonist terbutaline in Wistar rats over-expressing renal beta2-AR were compared with those of nontreated rats. Furthermore, we evaluated intrarenal beta2-AR expression in 34 children (age 2-15 y) and the changes in serum creatinine levels of 99 children (age 1-15 y) who received beta2-AR agonists. The animal study showed that the suppression of glomerular function by terbutaline was associated with a reduction in systemic blood pressure and over-expression of renal beta2-ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of terbutaline resulted in a high mortality rate after a lipopolysaccharide challenge. The clinical study showed that renal beta2-AR expression gradually increased with age and was up-regulated by steroid therapy. These findings indicate that the renal dysfunction caused by beta2-AR agonists can be explained, at least partly, by enhanced beta2-AR expression in the kidney. This may have important implications for the use of beta2-AR agonists in the treatment of sick children with, for example, steroid therapy or endotoxemia.

Renal hypouricemia in school-aged children: screening of serum uric acid level before physical training.

We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese girl who had exercise-induced acute renal failure (ARF). They experienced general fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical exercise at school. In case of the boy, abdominal pain subsided, but renal dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia before, she followed a doctor's guidance on prevention of ARF. Consequently, she was promptly diagnosed as having exercise-induced ARF associated with hypouricemia, and rapidly recovered from ARF within a week. The difference between their clinical courses suggested a possibility that previous laboratory evaluation of serum uric acid assisted in the management of exercise-induced ARF associated with hypouricemia. School-aged children, especially Japanese and Asian, may be advised to have their serum uric acid measured before starting physical training at school.

Adenoviral delivery of the beta2-adrenoceptor gene in sepsis: a subcutaneous approach in rat for kidney protection.

Successful gene therapy requires gene delivery that is efficient, has an optimal route of administration and has biosafety. The aims of the present study were to evaluate the safety and applicability of the subcutaneous delivery route for adenoviral transgenes containing the human beta(2)-adrenoceptor (adeno-beta(2)-AR) and to investigate whether this approach prevented renal dysfunction in a rat model of endotoxaemic shock induced by LPS (lipopolysaccharide). Subcutaneous administration of adeno-beta(2)-AR (a total of 10(10) viral particles) significantly increased beta-AR density in the kidney, lung and liver, but was without effect on physiological and plasma biochemical parameters. Moreover, this dose of virus did not cause any of the potential toxic responses of viral administration, such as inflammation and tissue TNF (tumour necrosis factor)-alpha expression. Although the LPS challenge caused a decrease in glomerular filtration rate, fractional excretion of sodium and renal beta-AR density in all groups, the reduction in renal function was significantly less in the rats given adeno-beta(2)-AR compared with non-treated rats. Thus, although further evaluation will be required, this initial study demonstrated that the subcutaneous injection of adeno-beta(2)-AR was efficient, comparatively non-pathogenic and potentially therapeutic to deal with acute renal failure associated with sepsis.

Suppression of endotoxin-induced renal tumor necrosis factor-alpha and interleukin-6 mRNA by renin-angiotensin system inhibitors.

The present study was designed to clarify the role of angiotensin II (Ang II) in modulating renal tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production and to investigate the effect of one dose of Ang II inhibitor on cytokines production following lipopolysaccharide (LPS) to cause endotoxemia. Two studies were performed: 1) Ang II was infused intravenously at a rate of 0.2 microg/kg per minute for 4 h in rats and then kidneys were collected to assay TNF-alpha and IL-6 mRNA levels; 2) Four-week-old Wistar rats pre-treated with angiotensin-converting enzyme inhibitor, enalapril, or type I Ang II-receptor antagonist, TCV-116, were injected with LPS (0.1, 0.5, 1.0 mg, i.p.), and then 2 or 4 h later, kidneys were collected to assay TNF-alpha, IL-6, renin and angiotensinogen mRNA levels. After a 4-h intravenous infusion of Ang II, renal TNF-alpha or IL-6 mRNA level significantly increased 1.9-fold or 2.1-fold (each P<0.05) to the control level, respectively. LPS stimulated TNF-alpha, IL-6 and angiotensinogen mRNA levels in the kidney but in rats given enalapril or TCV-116, LPS-induced IL-6 and TNF-alpha mRNA levels were completely suppressed (each P<0.05). This suggests that a single dose of renin-angiotensin system inhibitor suppressed renal IL-6 and TNF-alpha production and may prevent cytokine-induced renal damage during endotoxemia.

Role of angiotensin II-induced cAMP in mesangial TNF-alpha production.

Previous findings indicated that cAMP had an inhibitory effect of on tumour necrosis factor (TNF)-alpha production. Angiotensin II (Ang II) may activate the cAMP-protein kinase A (PKA) pathway in renal mesangial cells through synthesis of prostaglandins (PGs) and the possibility arises that inhibition of Ang II-induced cAMP formation might result in the overproduction of TNF-alpha in the cell and this hypothesis was tested in the present study. Rat mesangial cells were exposed to Ang II in the presence or absence of cyclooxygenase inhibitor (indomethacin) or cAMP-PKA inhibitor (H-89). Exposure of mesangial cell to Ang II (10(-6)M-10(-8)M) significantly increased intracellular cAMP level through type 1 Ang II receptor but had no effect on TNF-alpha protein release, transcriptional activity, or mRNA. However, following the addition of indomethacin or H-89, Ang II significantly increased TNF-alpha release, transcriptional activity, and mRNA level. These data suggested that in mesangial cells after blockade of cAMP-PKA by PG inhibition, Ang II was capable of stimulating TNF-alpha transcription which subsequently increased TNF-alpha mRNA accumulation and protein release.