Search

Interventional radiology procedures often involve lengthy exposure to fluoroscopy-derived radiation. We therefore devised a videofluoroscopic swallowing study (VFSS) procedure using a human phantom that proved to protect the patient and physician by reducing the radiation dose. We evaluated a new lead-shielding device and separately attached additional filters (1.0-, 2.0-, and 3.0-mm Al filters and a 0.5-mm Cu filter) during VFSS to reduce the patient's entrance skin dose (ESD). A monitor attached to the human phantom's neck measured the ESD. We also developed another lead shield (VFSS Shielding Box, 1.0-mm Pb equivalent) and tested its efficacy using the human phantom and an ionization chamber radiation survey meter with and without protection from scattered radiation at the physician's position on the phantom. We then measured the scattered radiation (at 90 and 150 cm above the floor) after combining the filters with the VFSS Shielding Box. With the additional filters, the ESD was reduced by 15.4-55.1%. With the VFSS Shielding Box alone, the scattered radiation was reduced by about 10% compared with the dose without additional shielding. With the VFSS Shielding Box and filters combined, the scattered radiation dose was reduced by a maximum of about 44% at the physician's position. Thus, the additional lead-shielding device effectively provided protection from scattered radiation during fluoroscopy. These results indicate that the combined VFSS Shielding Box and filters can effectively reduce the physician's and patient's radiation doses. [ABSTRACT FROM AUTHOR]

The present study compared renal ischemia-reperfusion (IR) injury in Dahl salt-sensitive (SS) rats that have a deficiency in the renal formation of 20-HETE versus CYP4A1 transgenic SS (SS.4A1) rats in which the renal production of 20-HETE is restored. The concentrations of free 20-HETE in the renal cortex and outer medulla were significantly greater in SS.4A1 than in SS rats. Renal 20-HETE levels rose to a greater extent in SS.4A1 than in SS rats following renal IR. Plasma creatinine level rose to 3.7 ± 0.1 in SS versus 1.8 ± 0.3 mg/dl in SS.4A1 rats (respectively, n=6) following 30 min of ischemia and 24 h reperfusion. The % of necrotic tubules and apoptotic cells were 4-fold higher in SS than in SS.4A1 rats. Administration of the 20-HETE synthesis inhibitor (HET0016, 10 mg/kg) abolished the resistance of SS.4A1 rats to renal IR injury and plasma creatinine level rose to 3.8 ± 0.1 mg/dl (n=6). Cortical blood flow in SS, SS.4A1 and HET0016 treated SS.4A1 rats immediately returned to control following IR. However, medullary blood flow in SS and HET0016 treated SS.4A1 rats fell to 30 % of control 3 h after IR (n=5), and it remained depressed for 24 h. In contrast, medullary blood flow did not decline following IR in SS.4A1 rats. Proximal intratubular pressure rose from 13 to approximately 40 mmHg, 2 h after IR in both SS and SS.4A1 rats. Proximal intratubular pressure remained much higher in SS than in SS.4A1 rats 24 h after IR (32 vs 19 mmHg). These data indicate that normalization of renal CYP4A activity and 20-HETE production opposes renal IR injury by preventing secondary fall in medullary blood flow and the prolonged renal medullary ischemia. [ABSTRACT FROM AUTHOR]

Exercise training (Ex) slows the progression of hypertension and renal failure in some animal models. We and other groups have reported that Ex ameliorated hypertension and renal dysfunction in spontaneously hypertensive rats. Since little has been reported on the effects of Ex on renal disorder in salt-sensitive hypertension, we investigated the effects of Ex on blood pressure and renal function in Dahl salt-sensitive (DS) rats. Six-week-old male DS rats were divided into three groups: 1) Normal salt (0.5% NaCl) diet (NS) (NS group, n=10), 2) High salt (8% NaCl) diet (HS) (HS group, n=11), 3) HS plus moderate Ex with treadmill running (HE group, n=11). After 8 weeks, HS induced severe hypertension, and Ex did not affect systolic blood pressure (114±3, 209±6 and 205±8 mmHg in the NS, HS and HE groups, respectively). Plasma creatinine was significantly higher in the HS and HE groups than in the NS group, but not different between the HS and HE groups (0.22±0.01, 0.44±0.03 and 0.40±0.03 mg/dl). Urinary protein and albumin significantly increased in the HS and HE groups, but these were significantly lower in the HE group compared with the HS group (Protein: 15.9±1.6, 432.8±36.8 and 327.2±22.3 mg/day. Albumin: 3.9±0.8, 195.2±15.2 and 154.2±11.1mg/day). Urinary TBARS, an index of oxidative stress, significantly increased in the HS and HE groups, but this was significantly lower in the HE group compared with the HS group (0.30±0.02, 0.75±0.06 and 0.53±0.03 mg/day); there was no significant difference in plasma TBARS among all groups. CYP4A1 and CYP4A2 protein expressions in the outer medulla were significantly lowered by 37% and 48% in the HS group compared with the NS group, and were significantly elevated by 40% and 150% in the HE group compared with the HS group. There was no significant difference in cortical CYP4A1 protein expression among all groups. Although there was no difference in cortical CYP4A2 between the NS and HS groups, it was significantly increased by 35% in the HE group compared with the HS group. These results suggest that Ex attenuated HS-induced proteinuria independently of blood pressure or plasma creatinine level in DS rats. The improvement of oxidative stress and CYP4A expression in the kidneys may contribute to the renoprotective effects of Ex in DS rats. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that inhibitors of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) protect against ischemia reperfusion injury (IRI) in the brain and heart. However, the role of endogenous 20-HETE in renal IRI has not been well characterized. The present study compared the susceptibility to IRI in Dahl salt-sensitive (S) rats in which the renal formation of 20-HETE is impaired versus that seen in normal Sprague-Dawley (SD) rats and in SS.5LEW 4A+ (4A+) congenic and SS.BN5 (BN5) consomic strains in which the CYP4A region of chromosome 5 was transferred from the Lewis or Brown Norway rats into the S genetic background. S, 4A+ and BN5 rats were fed a low salt diet and SD rats were fed a standard diet. IRI was induced by bilateral renal ischemia for 30 minutes followed by reperfusion. The 20-HETE production was measured using liquid chromatography-mass spectrometry (LC/MS). The renal production level of 20-HETE was significantly greater in SD, 4A+ and BN5 rats as compared to S rats and renal 20-HETE levels rose to a greater extent in these strains than in S rats following renal ischemia reperfusion. Plasma creatinine concentration rose to 3.7 ± 0.1 (n=6), 2.0 ± 0.4 (n=6), 1.9 ± 0.3 (n=6) and 2.2 ± 0.3 (n=6) mg/dl 24 hours following renal ischemia in S, 4A+, BN5 and SD rats, respectively. The kidney of S rats following IRI exhibited renal tubular necrosis and protein casts. The % of necrotic tubules in the corticomedullary regions of S rats (42.5 ± 3.5 %) was significantly higher than that seen in 4A+ (10.8 ± 3.8 %) or BN5 (10.2 ± 1.5 %) rats. The number of apoptotic tubular cells in the corticomedullary regions of S rats (125.3 ± 8.2 cells/field) was significantly higher than that seen in BN5 rats (46.8 ± 5.1 cells/field). Administration of the 20-HETE antagonist (6, 15-20-hydroxyeicosadecanoic acid) or the 20-HETE synthesis inhibitor (HET0016) abolished the resistance of 4A+ and BN5 rats to renal IRI and plasma creatinine levels rose to 4.0 ± 0.4 (n=4) and 3.8 ± 0.1 (n=4) mg/dl, respectively. The % of necrotic tubules respectively increased to 33.6 ± 6.9 % and 38.5 ± 5.5 % in 4A+ and BN5 rats and the number of apoptotic tubular cells increased to 119.2 ± 10.7 cells/field in BN5 rats. These data indicate that endogenously released 20-HETE plays a protective role in renal IRI. [ABSTRACT FROM AUTHOR]

Abnormal lipid metabolism is common in patients with hypertension and chronic renal failure. Angiotensin II (Ang II) treatment causes high blood pressure and lipid accumulation in the kidney of rats. However, the mechanism of the Ang II-induced lipid accumulation in the kidney is not fully clarified. The present study was designed to examine changes of fatty acid metabolism in the kidney of Ang II-treated rats. Male Sprague-Dawley rats were treated with vehicle or Ang II (400ng/kg/min) by using osmotic mini-pumps for 7 days. The protein expression of enzymes associated with fatty acid metabolism in the kidney was analyzed by using immunoblot ananlysis. After 7 days, Ang II treatment significantly increased the systolic blood pressure (112.0±2.8mmHg versus 134.6±3.4mmHg; P<0.01) and urinary albumin excretion (21.1±0.9 versus 473.8±143.7μg/mg creatinine; P<0.05), but did not affect plasma creatinine. Ang II treatment significantly decreased the medium-chain acyl-CoA dehydrogenase (MCAD), very long-chain acyl-CoA dehydrogenase (VLCAD) (mitochondrial β-oxidation enzymes), cytochrome P-450 (CYP)4A1, and CYP4A2 (microsomal ω-oxidation enzymes) expressions by 20%, 19%, 31% and 17% (P<0.01) in the cortex. It also significantly decreased the MCAD, CYP4A1, CYP4A2 by 38%, 55%, 54% (P<0.01) in the outer medulla, but did not affect the VLCAD expression. In addition, Ang II treatment decreased the peroxisome proliferator-activated receptor (PPAR-α; a nuclear receptor regulating fatty acid oxidation) expression by 30% (P<0.05) in the outer medulla. It did not affect the PPAR-α expression in the cortex and the PPAR-γ coactivator-1α (PGC-1α; a regulator of mitochondrial function) expression both in the cortex and medulla. These data indicate that Ang II down-regulates the MCAD, VLCAD, CYP4A and PPAR-α expressions in the kidney. The suppressed fatty acid oxidation by Ang II may probably cause the renal lipid accumulation, associated with the development of hypertensive kidney damage. [ABSTRACT FROM AUTHOR]

Alubuminuria is an aggravating factor for chronic kidney disease. Fatty acids bound to albumin are overloaded to the proximal tubules in alubuminuria and contribute to tubulointerstitial damage. It is known not only the β-oxidation ability but the ability of cytochrome P450 (CYP) metabolism of arachidonic acid (AA) is high in the kidney. Epoxyeicosatrienoic acids synthesized primarily by CYP2C and 20-hydroxyeicosatetraenoic acid synthesized by CYP4A affect tubular function and renal circulation. However, it isn’t clear CYP metabolism of AA would change in alubuminuria. The study tested changes of CYP metabolism of AA in the kidney of nephrotic rats. Sprague-Dawley rat (SD) and Nagase Analbuminemic rat (NAR) with inherited hypoalbuminemia were used and nephrotic syndrome was induced by Puromycin Aminonucleoside (PAN; 100 mg/kg, iv). Rats were randomly divided into four groups; (1) SD group; (2) SD treated with PAN group (PAN group); (3) NAR group; (4)NAR treated with PAN group (NAR+PAN group). Rats were killed on the 14th day and urinary 8OHdG, a marker of oxidative stress in the kidney, and urinary NAG, a marker of proximal tubular cell damage, were measured. The protein level of enzymes in the kidney was analyzed by Western blot and immunohistochemistry. Compared with the SD group, albuminuria, 8OHdG and NAG increased respectively to 847%, 154% and 903% in the PAN group, and Western blot showed the protein levels of CYP2C23 and CYP4A decreased to 45% and 49% without change of the protein level of PPARα, a nuclear receptor regulating fatty acid metabolism, in the PAN group. Immunohistochemistry showed the localization of CYP2C23 and CYP4A in the proximal tubule and confirmed the results by Western blot. Otherwise, we could find no difference in albuminuria, tubulointerstitial damage and the protein level of CYP2C23 between the NAR group and the NAR+PAN group. Compared with the NAR group, the protein level of CYP4A decreased to 68% in the NAR+PAN group. Alubuminuria caused tubulointerstitial damage and decreased the expressions of CYP2C23 and CYP4A in the nephrotic kidney. This study suggested the disorder of CYP metabolism of AA would affect renal circulation in alubuminuria and CYP4A would be affected by anything except alubuminuria in PAN rats. [ABSTRACT FROM AUTHOR]

It has been recently reported that the exercise training (Ex) increases nitric oxide (NO) production and NO synthase (NOS) expression not only in vasculatures but also in the kidney of spontaneously hypertensive rats (SHR) with the reduction of systemic blood pressure. To clarify the mechanism of the Ex-increased NOS expression, the impacts of inhibitors of NADPH oxidase and xanthine oxidase on the Ex-increased NOS activity and expression were examined in SHRs and Wistar-Kyoto rats (WKY). Five week-old, male SHR or WKY were trained with treadmill running. Apocynin (2 mmol/L in drinking water), an inhibitor of NADPH oxidase or allopurinol (1.5 mmol/L in drinking water), an inhibitor of xanthine oxidase was given for drug treatments. After 8 weeks, H2O2 and NO2/NO3 (NOx) in plasma and urine were measured. The NOS activity and expression were examined in the kidney cortex, the outer medulla, the inner medulla and thoracic aorta. In both SHR and WKY, the Ex significantly increased H2O2 and NOx in plasma and urine, NOS activity and endothelial and neuronal NOS (eNOS and nNOS) expressions in the kidney cortex, the outer medulla, the inner medulla and thoracic aorta (p<0.01 in each). Apocynin significantly decreased basal levels of H2O2 and NOx in plasma and urine, NOS activity and eNOS and nNOS expressions (p<0.01 in each) in the kidney sections and aorta of SHR, but did not affect all parameters in those of WKY. Apocynin blocked the Ex-induced changes of H2O2 and NOx levels and renal and aortic NOS activity and expression in WKY and aortic NOS activity and expression in SHR, but it did not block the Ex-induced changes of H2O2 and NOx levels or renal NOS activity and expression in SHR. In contrast to apocynin, allopurinol did not affect basal levels of all these parameters in SHR or WKY. Allopurinol blocked the Ex-induced changes of H2O2 and NOx levels and renal NOS expression in SHR but did not block the Ex- induced changes of aortic NOS expression in SHR or all parameters in WKY. These results indicate that the Ex-increased NOS activity and expression in aorta were mediated through NADPH oxidase in both SHR and WKY. The Ex-induced NOS activity and expression in the kidney were mediated through NADPH oxidase in WKY but through xanthine oxidase in SHR. [ABSTRACT FROM AUTHOR]

The incidence and severity of acute kidney injury is increased in patients with diabetes and with aging. However, the mechanisms involved have not been clearly established. The present study examined the effects of aging and diabetes on the severity of renal ischemia-reperfusion (IR) injury in Sprague-Dawley (SD) and type 2 diabetic (T2DN) rats. T2DN rats develop diabetes at 3 mo of age and progressive proteinuria and diabetic nephropathy as they age from 6 to 18 mo. Plasma creatinine levels after bilateral IR were significantly higher (3.4 ± 0.1 mg/dl) in 18-mo-old elderly T2DN rats than in middle-aged (12 mo) T2DN rats with less severe diabetic nephropathy or young (3 mo) and elderly (18 mo) control SD rats (1.5 ± 0.2, 1.8 ± 0.1, and 1.7 ± 0.1 mg/dl, respectively). Elderly T2DN rats exhibited a greater fall in medullary blood flow 2 h following renal IR and a more severe and prolonged decline in glomerular filtration rate than middle-aged T2DN and young or elderly SD rats. The basal expression of the adhesion molecules ICAM-1 and E-selectin and the number of infiltrating immune cells was higher in the kidney of elderly T2DN than age-matched SD rats or young and middle-aged T2DN rats before renal IR. These results indicate that elderly T2DN rats with diabetic nephropathy are more susceptible to renal IR injury than diabetic animals with mild injury or age-matched control animals. This is associated with increased expression of ICAM-1, E-selectin and immune cell infiltration, renal medullary vasocongestion, and more prolonged renal medullary ischemia.

Exit-site infection poses a risk for peritonitis and can shorten peritoneal dialysis (PD) vintage. A loose fit of the skin around the catheter at the exit site can push bacteria surrounding the catheter into the subcutaneous tunnel. Negative-pressure wound therapy (NPWT) has been used to hasten healing of the wound after an operation or to treat pressure ulcers. We hypothesized that NPWT could speed the healing of the exit site and tighten the fit of the skin around the catheter. Using a V.A.C. Therapy system [vacuum-assisted closure (KCI, San Antonio, TX, U.S.A.)], NPWT was therefore applied in 9 patients for 1 - 2 weeks after the PD catheter insertion operation. Results in those patients were compared with results in patients who did not receive NPWT.The healed exit site was classified as either tightly fitted (when the skin was tightly connected around the PD catheter) or loosely fitted (when the skin was not tightly connected around the catheter). The relevant data were retrieved from the medical record and analyzed retrospectively.Patients who received NPWT had a tight exit site after 1 - 2 weeks. Those who did not receive NPWT did not have a tight exit site after 1 - 2 weeks. No bleeding was observed in patients receiving NPWT. Bleeding from the exit site after the catheter insertion operation was observed in 3 patients not receiving NPWT.Because we use a fine trocar to make the subcutaneous catheter tunnel, bleeding from the vasculature can often be observed. That bleeding could be minimized with the application of NPWT. Negative pressure could also hasten wound healing and result in a tight fit of the skin around the catheter within in 1 - 2 weeks compared with the 1 month typically required with the use of conventional film dressings.Negative-pressure wound therapy is beneficial for creating a tight fit of the skin to the catheter within 1 - 2 weeks and might reduce the number of exit-site and tunnel infections, which could result in a reduction in the peritonitis rate.