PURPOSE: iNOS expression in vascular smooth muscle cells (VSMC) causes the development of septic shock, and multiple organ dysfunction syndrome (MODS). For the inhibition of iNOS expression, glucocorticoids are known to inhibit iNOS expression but immunosuppression decreases its clinical availability. Recently, aspirin was reported to inhibit iNOS expression, but the mechanism and effectiveness are still unclear. In this investigation, on aspirin, several non steroidal antiinflammatory drugs (NSAIDs) were applied to clarify the inhibitory mechanism of iNOS expression and NO production in lipopolysaccharide (LPS) treated VSMCs. METHOD: VSMCs were primarily cultured from rat aorta and confirmed by immunocytochemistry of anti-smooth muscle myosin antibody. LPS, an inducer of iNOS, and NSAIDs, such as aspirin, indomethacin, ketoprofen sodium salicylate and acetaminophen were used. The concentrations of nitrite in culture media following the addition of LPS with a 1-hour pretreatment of NSAIDs were measured by spectrophotometry with griess reaction. Western blot and RT-PCR for iNOS protein and iNOS mRNA, respectively, were performed. RESULT: Acetaminophen had no effect on the inhibition of nitrite production. NSAIDs, especially ketoprofen and sodium salicylate, showed a significant inhibitory effect on nitrite production. In their mechanism, all the NSAIDs in present study inhibited iNOS mRNA and protein expression. CONCLUSION: These results suggest that the inhibitory mechanism on iNOS expression of NSAIDs is due to the inhibition of iNOS mRNA expression and subsequent inhibition of iNOS protein expression.
Acetaminophen* ; Animals ; Anti-Inflammatory Agents, Non-Steroidal* ; Aorta ; Aspirin ; Blotting, Western ; Culture Media ; Glucocorticoids ; Immunohistochemistry ; Immunosuppression ; Indomethacin ; Ketoprofen ; Multiple Organ Failure ; Muscle, Smooth, Vascular* ; Myosins ; Rats ; RNA, Messenger ; Shock, Septic ; Sodium Salicylate ; Spectrophotometry

In order to investigate the expression patterns of the transforming growth factor (TGF)beta isoforms in the internal ear, an immunohistochemical study of rat embryos was performed. Rat embryos were taken on the 13th, 15th, 17th, and 19th day after conception and their internal ears were immunohistochemically stained against TGF beta1, beta2, and beta3. As a result, the 13-day-old embryo showed a very weak positivity to TGF beta1. After the 15th day of pregnancy, no reactivity to TGF beta1 was defected. Immunoreactivity to TGF beta2 was observed from the 15th day of pregnancy throughout the rest of the period. The ampulla of the semicircular canal and the cochlear duct showed a notably strong immunohistochemical reaction. A strong reaction to TGF beta3 was observed on the 15th day of pregnancy. However, no positive reactions were observed thereafter. A strong immunoreactivity was observed especially on the apical cytoplasms, the surfaces of the epithelial cells, and basement membranes of the cochlear duct, as well as the semicircular canals of the developing internal ear of rat embryo.
Animals ; Ear, Inner/embryology/*metabolism ; Embryo/embryology/*metabolism ; Female ; Immunohistochemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Transforming Growth Factor beta/*biosynthesis

STUDY DESIGN: A retrospective study OBJECTIVES: To compare the radiological and clinical outcomes of three surgical methods SUMMARY OF LITERATURE REVIEW: There were many proposed surgical treatments for lumbar degenerative kyphosis but the best treatment is still controversial. MATERIALS AND METHODS: Thirty three patients (all female) had undergone surgery. The mean age at surgery was 61.2. The average follow-up period was 34.7 months. The patients were divided into three groups. Group A included 7 cases with a correction by a posterior osteotomy, Group B included 15 with a posterior correction without an osteotomy, and Group C included 11 with combined anterior-posterior surgery. The radiographic measurements of lumbar lordosis, upper lumbar lordosis, lower lumbar lordosis, and pelvic tilt were performed before surgery, after surgery, and at the final follow-up visit. The loss of correction, complication rates and the clinical results were also compared. RESULTS: Postoperative correction of the lumbar and lower lumbar lordosis were significantly higher in group A and C than group B. The correction of upper lumbar lordosis was significantly higher in group A than group C. On the final follow-up, there was no significant difference in the loss of correction and clinical results between the three groups. The number of cases with complications in groups A, B and C was 4 (57%), 2 (13.3%) and 2 (18.2%), respectively. Two patients in group A required additional surgery. CONCLUSIONS: Groups A and C were more effective than posterior-only correction. There was no significant difference in the clinical results between the three groups but complication rate was higher in Group A than the other groups. Combined anterior and posterior surgery can be a safe and effective method for correction.
Animals ; Follow-Up Studies ; Humans ; Kyphosis ; Lordosis ; Osteotomy ; Retrospective Studies

BACKGROUND: It was previously known that anuric acute kidney injury (AKI) is uncommon and its occurrence suggests complete ureteral obstruction, shock, or a major vascular event. As the epidemiology of AKI has significantly changed over the past decade, it is possible that the incidence, etiology, or clinical characteristics of anuric AKI have also changed. METHODS: A prospective cohort study was conducted that included all patients undergoing renal replacement therapy (RRT) for AKI during a 2-year period in a tertiary hospital. Patients were classified as having anuric, oliguric, or nonoliguric AKI based on their volume of urine when RRT started using the modified Acute Kidney Injury Network criteria. RESULTS: Of the 203 patients included in the study, 21.2% met the criteria for anuric AKI. Septic and postoperative AKI were the main causes of anuric AKI, with 60.5% of incidences occurring in hospital. Anuric AKI was associated with a younger age, a lower prevalence of pre-morbid chronic kidney disease and diabetes, more frequent continuous RRT requirement, and multi-organ dysfunction. In addition, patients with anuric AKI had a higher rate of in-hospital mortality and long-term dependence on RRT than patients with nonanuric AKI. CONCLUSION: Anuric AKI is common, with sepsis as the main etiological insult, and is associated with adverse outcomes among patients with AKI who require RRT.
Acute Kidney Injury* ; Anuria* ; Cohort Studies ; Epidemiology ; Hospital Mortality ; Humans ; Incidence ; Oliguria ; Prevalence ; Prospective Studies ; Renal Insufficiency, Chronic ; Renal Replacement Therapy ; Sepsis ; Shock ; Tertiary Care Centers ; Ureteral Obstruction

PURPOSE: Cardiovascular diseases are a common cause of mortality in patients with end stage renal disease and are associated with vascular calcification (VC) and arterial stiffness. In addition to high turnover bone disease, there is substantial evidence that low levels of serum intact PTH (iPTH) are associated with vascular calcium deposition. The objective was to evaluate the association of iPTH levels with VC, arterial stiffness, and to identify risk factors contributing to VCs and arterial stiffness. METHODS: One hundred five hemodialysis (HD) patients were divided into three groups according to iPTH levels: A, <150 pg/mL; B, 150< or =and< or =400 pg/mL; and C, >400 pg/mL. The simple vascular calcification score (SVCS) was obtained by X-ray; the brachial ankle-pulse wave velocity (ba-PWV) and the serum fetuin-A level was mesured. RESULTS: Patients in group A were older and had a higher SVCS, a prevalence of diabetes, and an increased arterial stiffness. Severe VCs (SVCS> or =3) were associated with the low iPTH group (iPTH<150)/a higher CRP/a lower diastolic blood pressure (DBP)/diabetes/ increased arterial stiffness/older age and a lower serum fetuin-A level. The log [ba-PWV] had a positive correlation with age, systolic blood pressure (SBP)/DBP/PP/CRP/presence of diabetes and low iPTH and a negative correlation with serum albumin. Based on multivariate analysis, the low iPTH group and diabetes were identified as independent risk factors of severe VC and age/SBP/CRP and diabetes were risk factors for arterial stiffness. CONCLUSION: Low iPTH levels and/or diabetes had a greater risk of developing VCs and age/SBP/CRP/diabetes were associated with increased arterial stiffness in HD patients.
alpha-2-HS-Glycoprotein ; Blood Pressure ; Blood Vessels ; Bone Diseases ; Calcium ; Cardiovascular Diseases ; Humans ; Kidney Failure, Chronic ; Multivariate Analysis ; Parathyroid Hormone ; Prevalence ; Renal Dialysis ; Risk Factors ; Serum Albumin ; Vascular Calcification ; Vascular Stiffness

PURPOSE: In this study, the etiology and the change of clinical characteristics of hyponatremia, in relation to the increased used of thiazide diuretics, have been assessed. METHODS: To perform a retrospective cohort study, a total sum of 322 patients who have been admitted in a single tertiary referral hospital between 2004 and 2009, were included. RESULTS: The most common cause of hyponatremia was due to thiazide diuretics (37.6%). Among the 121 patients who suffered from thiazide induced hyponatremia, 60 (48.0%) patients took combination thiazide. The incidence of hyponatremia has shown a tendency to increase from 2004 to 2009 (trend test, p<0.001). The incidence of hyponatremia due to the use of combination types has also increased (trend test, p<0.001). Thiazide induced hyponatremia showed no difference when compared to hyponatremia due the other causes, except the fact that the portion of female patients was higher (73.6% vs 64.6%, p<0.001), mean age was older (74.7 vs 69.9 years-old, p<0.001), and incidence of cerebrovascular accident was also higher (19.8% vs 6.5%, p<0.001). CONCLUSION: The use of thiazide is increasing and hence thiazide-induced hyponatremia is also increasing. This is thought to be particularly related to the increase of thiazide-combined drugs. Thiazideinduced hyponatremia shows a higher incidence in old age, female sex and those who have a history of a cerebrovascular event. Hence more caution is needed when using thiazide diuretics as antihypertensives, and plasma sodium levels should be monitored carefully.
Antihypertensive Agents ; Cohort Studies ; Diuretics ; Female ; Humans ; Hyponatremia ; Incidence ; Plasma ; Retrospective Studies ; Sodium ; Sodium Chloride Symporter Inhibitors ; Stroke ; Tertiary Care Centers

BACKGROUND: A decreased level of serum arginine vasopressin(AVP) and an increased sensitivity to an exogenous AVP is expected in patients with septic shock who often require a high infusion rate of catecholamines. The goal of the study was to determine whether an exogenous AVP infusion to the patients with septic shock would achieve a significant decrement in infusion rate of catecholamine vasopressors while maintaining hemodynamic stability and adequate urine output. METHODS: Eight patients with septic shock who require a high infusion rate of norepinephrine had received a trial of 4-hour AVP infusion with simultaneous titration of norepinephrine. Hemodynamic parameters and urine output were monitored during the AVP infusion and the monitoring continued up to 4 hours after the AVP infusion had stopped. RESULTS: Mean arterial pressure showed no significant changes during the study period(p=0.197). Norepinephrine infusion rate significantly decreased with concurrent AVP administration(p=0.001). However, beneficial effects had disappeared after the AVP infusion was stopped. In addition, hourly urine output showed no significant changes throughout the trials(p=0.093). CONCLUSION: Concurrent AVP infusion achieved the catecholamine vasopressor sparing effect in the septic shock patients, but there was no evidence of the improvement of renal function. Further study may be indicated to determine whether AVP infusion would provide an organ-protective effect to the septic shock patients.
Arginine* ; Arterial Pressure ; Catecholamines ; Hemodynamics ; Humans ; Norepinephrine ; Shock, Septic*

BACKGROUND/AIMS: The potential physiologic roles of Klotho in acute kidney injury (AKI) have recently been demonstrated in animal models. However, to date, there have been no human studies investigating the expression of renal Klotho in AKI. METHODS: We retrospectively collected biopsy specimens and clinical data of AKI patients between January 2001 and December 2012. Klotho expression was determined by immunohistochemical staining, and the clinical-pathological correlation was examined. RESULTS: Among the 34 patients diagnosed with acute tubular necrosis or acute tubulointerstitial nephritis, 21 patients without chronic histological lesions were included. The mean age was 37.3 +/- 18.5 years and the mean peak creatinine level was 8.2 +/- 5.5 mg/dL. In total, 10 patients (47.6%) received temporary renal replacement therapy (RRT); however, 17 patients (81%) showed functional recovery with creatinine levels of < 1.3 mg/dL after 1 month. The intensity of Klotho expression was scored as a percentage of Klotho-positive area. The renal Klotho score showed a significant negative correlation with the initial or peak creatinine level. When the patients were divided into three groups according to the Klotho score (low, middle, high), the low group had a significantly higher peak creatinine level and a more frequent requirement for RRT. However, the Klotho score was not a significant predictor of renal recovery. CONCLUSIONS: The results demonstrated that renal Klotho expression in humans decreased significantly according to the severity of AKI, regardless of the etiology, and that low expression was associated with a poor short-term outcome.
Acute Kidney Injury/diagnosis/etiology/*metabolism/physiopathology/therapy ; Adolescent ; Adult ; Biomarkers/analysis ; Biopsy ; Down-Regulation ; Female ; Glucuronidase/*analysis ; Humans ; Immunohistochemistry ; Kidney/*chemistry/pathology/physiopathology ; Kidney Tubular Necrosis, Acute/diagnosis/etiology/*metabolism/physiopathology/therapy ; Male ; Middle Aged ; Necrosis ; Predictive Value of Tests ; Recovery of Function ; Renal Replacement Therapy ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Time Factors ; Treatment Outcome ; Young Adult

BACKGROUND: Although emerging evidence suggests that intra-abdominal hypertension (IAH) is a predictor of the development of acute kidney injury (AKI), it remains unclear whether the presence of IAH is a predictor of prognosis in patients with AKI. The purpose of this study was to assess whether the presence of IAH could predict prognosis in critically ill patients with AKI. The prognostic value of urinary biomarkers was also determined. METHODS: In this prospective observational study, we enrolled 57 patients with established AKI, who were admitted to the intensive care unit between February 2012 and June 2014. IAH was defined as a sustained elevation in intra-abdominal pressure of > or =12 mmHg, in three consecutive measurements performed daily on the first 3 days. Urinary neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein, and simplified acute physiology score II score at the time of admission were also examined. RESULTS: IAH was observed in 78.9% of patients. The in-hospital mortality was 21.1%, and renal recovery during hospitalization was achieved in 40.4% of patients. Although high urinary NGAL [odds ratio (OR), 1.015] and liver-type fatty acid-binding protein (OR, 1.003) were found to be independent predictors of renal recovery, IAH was not. High urinary NGAL (OR, 1.003) and a high simplified acute physiology score II score (OR, 1.102) were independent predictors of in-hospital mortality, while IAH or urinary liver-type fatty acid-binding protein was not. CONCLUSION: Although IAH is prevalent in critically ill patients with AKI, it did not predict AKI prognosis. However, urinary NGAL was found to be a useful predictor of both renal recovery and in-hospital mortality.
Acute Kidney Injury* ; Biomarkers ; Critical Illness* ; Hospital Mortality* ; Hospitalization ; Humans ; Intensive Care Units ; Intra-Abdominal Hypertension* ; Lipocalins ; Neutrophils ; Observational Study ; Physiology ; Prognosis ; Prospective Studies

BACKGROUND: Pulmonary hypertension (PHT) is a recently recognized complication of chronic kidney disease. In this study, we investigated the association between PHT, peripheral vascular calcifications (VCs), and major cardiovascular events. METHODS: In this retrospective study, we included 172 end-stage renal disease (ESRD) patients undergoing dialysis [hemodialysis (HD)=84, peritoneal dialysis=88]. PHT was defined as an estimated pulmonary artery systolic pressure >37 mmHg using echocardiography. The Simple Vascular Calcification Score (SVCS) was measured using plain radiographic films of the hands and pelvis. RESULTS: The prevalence of PHT was significantly higher in HD patients (51.2% vs. 22.7%). Dialysis patients with PHT had a significantly higher prevalence of severe VCs (SVCS> or =3). In multivariate analysis, the presence of severe VCs [odds ratio (OR), 2.68], mitral valve disease (OR, 7.79), HD (OR, 3.35), and larger left atrial diameter (OR, 11.39) were independent risk factors for PHT. In addition to the presence of anemia, severe VCs, or older age, the presence of PHT was an independent predictor of major cardiovascular events in ESRD patients. CONCLUSION: The prevalence of PHT was higher in HD patients and was associated with higher rates of major cardiovascular events. Severe VCs are thought to be an independent risk factor for predicting PHT in ESRD patients. Therefore, in dialysis patients with PHT, careful attention should be paid to the presence of VCs and the occurrence of major cardiovascular events.
Anemia ; Blood Pressure ; Cardiovascular Diseases ; Dialysis* ; Echocardiography ; Hand ; Humans ; Hypertension, Pulmonary* ; Kidney Failure, Chronic ; Mitral Valve ; Multivariate Analysis ; Pelvis ; Prevalence ; Pulmonary Artery ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors ; Vascular Calcification* ; X-Ray Film