Renal nitrate clearance in chronic kidney disease.

BACKGROUND: Nitric oxide (NO) is rapidly oxidised in humans to nitrite and nitrate, with nitrate being present in much greater abundance. These oxidation products can be recycled back into nitric oxide via a complex entero-salivary pathway, thus preserving NO activity. Approximately 65% of circulating nitrate is excreted in the urine in 48 h, with the excretory pathway of the remainder unknown. The effect of declining renal function on nitrate clearance is unknown METHODS: Forty five subjects, 21 M, 24F, median age 69 (range 27-75 years) with renal function assessed by CKD-EPI eGFR between 9 and 89 ml/min/1.73 m2 completed the study. Following a 24 h low nitrate diet a microplate spectrophotometric method was employed to measure plasma nitrate concentration and 24 h urinary nitrate excretion were measured to determine renal nitrate clearance. RESULTS: There was a strong positive correlation between urinary nitrate clearance and eGFR, (Spearman R = 0.7665, p < 0.0001) with a moderate negative correlation between plasma nitrate concentration and CKD-EPI eGFR, (Spearman's R = -0.37, p = 0.012). There was a trend between fractional excretion of nitrate and CKD-EPI eGFR (ml/min/1.73 m2) Spearman's R 0.27, p = 0.07 though this did not reach statistical significance. Plasma nitrate concentration and serum creatinine concentration were positively correlated, Spearman's R = 0.39, p = 0.008. CONCLUSIONS: We have observed a strong positive association between renal nitrate clearance and renal function such that plasma nitrate rises as renal function falls. Fractional excretion of nitrate appears to decline as renal function falls. As such, urinary nitrate excretion is unlikely to be a reliable marker of endogenous NO synthesis in settings where renal function is altered.

The establishment of an anaesthetist-managed intraoperative neurophysiological monitoring service and initial outcome data.

Neurophysiological monitoring has been recommended to reduce the risk of neurological damage during a wide variety of surgeries. While the concept of an anaesthesia-led intraoperative neurophysiological monitoring (IONM) service is not new, the quality of this service provision has not been studied. In this article, we present our experience with the establishment of this service, and the results of our audit of 302 cases monitored over the initial four years. Our results identified that an anaesthesia-led IONM service was able to achieve a reliable signal in 95.4% of cases and capture significant alerts in 15.6% of these cases with sensitivity, specificity, false positive and negative rates consistent with published data. Our results indicate an anaesthesia-led IONM service is effective in identifying patients at an increased risk of an adverse outcome.

Forward and reverse mapping for milling process using artificial neural networks.

The data set presented is related to the milling process of AA6061-4.5%Cu-5%SiCp composite. The data primarily concentrates on predicting values of some machining responses, such as cutting force, surface finish and power utilization utilizing using forward back propagation neural network based approach, i.e. ANN based on three process parameters, such as spindle speed, feed rate and depth of cut.The comparing reverse model is likewise created to prescribe the ideal settings of processing parameters for accomplishing the desired responses as indicated by the necessities of the end clients. These modelling approaches are very proficient to foresee the benefits of machining responses and also process parameter settings in light of the experimental technique.

Fault tolerant mobile sensor node traversal schemes based on hexagonal coverage.

Mobile sensor nodes (MSNs) are equipped with locomotive can move around after having been deployed. They are equipped with limited energy. A large portion of energy is drained during the traversal. In order to extend the life time of a MSN, the traveling distance must be minimized. Region of interest (ROI) is covered with multiple MSNs using coverage based pattern movement. When a group of MSNs are deployed to cover a given ROI, all the deployed MSNs should travel an approximately equal distance. Otherwise, the MSN which travels longer distance depletes more energy compared to the MSN which travels a shorter distance. In this work we show that, ROI partition plays great role in hole free coverage and makes the MSNs have optimized movement cost with fault tolerant support.

Renal vasculitis: increasingly a disease of the elderly?

BACKGROUND/AIMS: The majority of patients presenting to our district general hospital with renal vasculitis are elderly. Older patients respond less well to treatment and have a poorer prognosis. We investigated the relationship between age and outcome of renal vasculitis in our centre and examined the evidence regarding treatment of elderly patients with this condition. METHODS: Patients presenting over a 2-year period with renal vasculitis were identified by clinical and histological features and by antineutrophil cytoplasmic autoantibody positivity. They were followed for a mean of 15 months and outcomes were recorded. Results were compared with published studies. RESULTS: The mean age at presentation of 21 patients was 69 years. Forty-eight percent required dialysis and there was a 33% overall mortality. The mean age of patients in previous treatment studies has been between 50 and 55 years. CONCLUSIONS: The greater severity of disease at presentation and poorer outcome than previously described is likely to be due to the high proportion of elderly patients. The incidence of vasculitis is increasing in the elderly but as this group has been poorly represented in clinical trials in renal vasculitis, applying the findings of these trials to their treatment may be hazardous. Future research should determine which treatments are safe and effective in the elderly.

Poly(DL-lactide-co-glycolide) microporous microsphere-based depot formulation of a peptide-like antineoplastic agent.

In the present investigation, a poly(DL-co-glycolide) (PLGA)-based, microspheric depot system for bleomycin (BLM) has been formulated, and the same has been evaluated in-vivo in C57BL/6J mice bearing transplantable melanoma B16F1 murine solid tumour. The microparticulate delivery systems were formulated employing a water-in-oil-in-water (W/O/W) emulsion-solvent evaporation technique and characterized in-vitro. The microspheres were injected subcutaneously to form a drug depot at the site of injection in mice bearing experimental tumours and the drug was continuously infused into the systemic circulation with progressive biodegradation. The drug-loaded microspheres exhibited improved pharmacodynamic efficacy, as evidenced by retarded tumour growth kinetics. Preliminary pharmacokinetic studies illustrated controlled release of the drug into the systemic circulation over the study period to exert an anti-neoplastic action. These studies demonstrated the feasibility of employing a PLGA-based microparticulate system as an effective biodegradable, injectable, depot-forming therapeutic system for long-term administration of anti-neoplastic agents.

Modifying influence of enalaprilat on mesangial cell DNA synthesis induced by hydrogen peroxide.

This study examined the effect of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induced by H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5-100 mumol/l) alone and together with combinations of H2O2 (3 daily pulses of 10(-6) mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [3H]thymidine (3H-TdR) incorporation. Enalaprilat alone had no effect on MC DNA synthesis. Stimulation of MC by H2O2, PDGF and IL-6 alone resulted in increases in 3H-TdR of 4936.6 +/- 1147.5, 5640.5 +/- 1537.6 and 4413.5 +/- 998.4 cpm, respectively (P < 0.05 above control). Only 2.5 mumol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H2O2 + PDGF or H2O2 + IL-6 resulted in increases of 3H-TdR of 6471.9 +/- 1785.1 and 5507.2 +/- 1270 cpm, respectively (P < 0.05 above control). Addition of enalaprilat with either H2O2 + PDGF or H2O2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5-100 mumol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.

Mesangial cell DNA synthesis induced by hydrogen peroxide, interleukin-6, and platelet-derived growth factor: effects of indomethacin and dazmegrel.

This study indirectly examined the role of prostanoids (PG) in mediating rat mesangial cell (MC) DNA synthesis induced by hydrogen peroxide (H2O2), interleukin 6 (IL-6), and platelet-derived growth factor (PDGF). MC were exposed to three daily pulses of 10(-6) mol/l H2O2 alone or in combination with IL-6 (5 ng/ml) or PDGF (10 ng/ml). In order to examine (indirectly) the role of PG in mediating changes in MC DNA synthesis, indomethacin (1.5 x 10(-5) mol/l) or the thromboxane A2 synthetase inhibitor Dazmegrel (10(-5) mol/l) was added to the medium and DNA synthesis assessed after 72 h using 3H-thymidine incorporation (3H-TdR). Stimulation of MC by H2O2 alone resulted in an increase in 3H-TdR of 34.7 +/- 5.5% (p < 0.01). H2O2 enhanced the mitogenic effects of IL-6 and PDGF, 3H-TdR increasing by 52 +/- 12.1% (p < 0.01) and 100 +/- 21% (p < 0.001), respectively. Indomethacin suppressed the DNA synthesis induced by H2O2 alone, 3H-TdR decreasing by 33 +/- 12% (p < 0.05). Indomethacin also reduced the mitogenic response to H2O2 plus IL-6 and H2O2 plus PDGF by 91 +/- 17 and 97 +/- 12%, respectively (p < 0.05). Dazmegrel reduced 3H-TdR when MC were exposed to H2O2 alone by 31.8 +/- 16% (p < 0.05) and when combined with IL-6 or PDGF by 80 +/- 26 and 120 +/- 13%, respectively (p < 0.05). These data suggest that the pathways through which H2O2-induced growth of MC is mediated appear, at least in part, to involve PG, particularly thromboxane A2.

Interactions of hydrogen peroxide with interleukin-6 and platelet-derived growth factor in determining mesangial cell growth: effect of repeated oxidant stress.

1. This study examined the influence of H2O2, interleukin-6 and platelet-derived growth factor on the proliferation of rat mesangial cells. Mesangial cells were exposed to either a single pulse or three daily pulses of H2O2 (10(-8)-10(-4) mol/l), alone or in combination with interleukin-6 (5 ng/ml) and/or platelet-derived growth factor (10 ng/ml). Proliferation was assessed after 24 h and 72 h of incubation using [3H]thymidine incorporation and cell counts. 2. Although one pulse of H2O2 had no significant effect on mesangial cell proliferation, three daily pulses of 10(-6) mol/l H2O2 resulted in a significant increase in [3H]thymidine incorporation of 31 (52.6, 10.3)% (median and 75th-25th interquartile range) (P < 0.001). Both interleukin-6 and platelet-derived growth factor were also mitogenic to mesangial cells, [3H]thymidine incorporation increasing by 19 (36.7, -6.7)% (P < 0.05) and 53.5 (107, 21.9)% (P < 0.001), respectively. The mitogenic effect of interleukin-6 was enhanced by 10(-6) mol/l H2O2 [49.9 (77.7, 12.3)%] (P < 0.01), whereas the addition of 10(-6) mol/l H2O2 to platelet-derived growth factor resulted in a summated increase in [3H]thymidine incorporation of 82.7 (113, 57.4)% (P < 0.001). Incubation with all three substances simultaneously resulted in down-regulation of growth compared with H2O2 plus platelet-derived growth factor by 55.4 (77.7, 10.3)% (P < 0.05). 3. These findings suggest that reactive oxygen species may play a major role in determining the mesangial cell proliferation that occurs in certain forms of glomerulonephritis, acting either alone or in combination with other growth factors.

Oxidant stress and glomerular prostanoid production: influence of angiotensin converting enzyme inhibition.

1. The effect of H2O2 (4.7 x 10(-9) -4.7 x 10(-3) M) on prostanoid production by isolated glomeruli from normotensive (WKY) and, spontaneously hypertensive rats (SHR) has been studied. 2. Oxidant stress significantly increased synthesis of prostaglandin E2 (PGE2), I2 (PGI2) and thromboxane A2 (TxA2) by glomeruli from both strains whereas the ratio (PGE2 + PGI2)/TxA2 increased in only SHR. 3. Pre-incubation of glomeruli with the angiotensin converting enzyme inhibitors captopril or lisinopril, had virtually no effect on H2O2-induced synthesis of individual prostanoids nor on the ratio (PGE2 + PGI2)/TxA2 by glomeruli from either WKY or SHR. 4. The findings suggest that H2O2-induced changes in glomerular function may be mediated, in part, by PGs but fail to support the suggestion that the ability of ACEI to protect glomeruli from H2O2-induced damage is determined by PGs.