[Show abstract][Hide abstract] ABSTRACT: Pneumatosis intestinalis is a characteristic imaging phenomenon indicating the presence of gas in the bowel wall. The link between pneumatosis intestinalis and various kinds of autoimmune diseases has been reported anecdotally, while information regarding the cases with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis complicated by concurrent pneumatosis intestinalis is lacking. In this report, we describe our serendipitous experience with one such case of pneumatosis intestinalis in a patient with ANCA-associated glomerulonephritis. We also discuss several therapeutic concerns that arose in the current case, which had an impact on the pathogenesis of the disease.
Preview · Article · Aug 2015 · Clinical Medicine Insights: Case Reports
[Show abstract][Hide abstract] ABSTRACT: Acute poststreptococcal glomerulonephritis (APSGN) is a well-established disease. Although various immune responses are thought to be involved in the pathogenesis of APSGN, the disease has a self-limiting nature in clinical practice, despite the presence of severe acute symptoms. We herein report the case of a 78-year-old woman with APSGN who developed primary biliary cirrhosis (PBC) after achieving remission of renal manifestations, including anasarca and elevation of serum creatinine, indicating that persistent alterations in the immune system can cause extrarenal disorders. This case provides insights into the appropriate clinical management of ASPGN and pathogenesis of PBC.
Full-text · Article · Aug 2015 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: We herein report the case of a 75-year-old man who developed an increased serum creatinine level (4.93 mg/dL) and oliguria with massive proteinuria (7.14 g/day) on the second day after a single oral administration of high-dose (56 mg) minodronate. The histology of a renal biopsy showed one area of glomerular sclerosis among 20 glomeruli with global foot process effacement of podocytes and mild infiltration of lymphocytes and eosinophils into the interstitial space. Acute kidney injury in nephrotic syndrome due to focal segmental glomerular sclerosis induced by minodronate was diagnosed. Following cessation of minodronate without the administration of immunosuppressive agents, the patient's renal function and proteinuria markedly improved.
No preview · Article · Jun 2013 · Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Central venous stenosis (CVS) is a serious complication for chronic hemodialysis (HD) patients. Previous reports of CVS have focused on prior central venous catheterization, because of the higher prevalence and potential for prevention of such an event. However, recent studies have demonstrated that CVS may also develop without a history of central venous catheterization. Although information about the etiological backgrounds regarding the development of CVS without previous central venous catheterization have gradually accumulated, the clinical impact of the chronic compression of the central venous system by the surrounding structures, which may likely determine the central venous susceptibility to CVS, remains poorly understood. This study proposes the hypothesis that the combination of chronic venous compression at the level of thoracic outlet characterized by the natural physique and elevated venous flow induced by the creation of vascular access should be evaluated as a potential factor for the development of CVS, since they may accelerate the development of venous stenosis, presumably through the stimulation of intimal hyperplasia, and thereby the subclavian venous susceptibility to CVS should be determined.
No preview · Article · Oct 2012 · Medical Hypotheses
[Show abstract][Hide abstract] ABSTRACT: Aim:
Low free triiodothyronine (fT3) has been associated with the presence of malnutrition-inflammation syndrome in patients with end-stage renal disease (ESRD) and decreased overall survival in ESRD. Since thyroid hormone has a particular effect on body fluid status, we hypothesized that hemodialysis patients with low-T3 syndrome might have interstitial edema. In this study, we examined the relationship between levels of thyroid hormone and body composition parameters in Japanese hemodialysis patients.
The subjects were 52 patients on maintenance hemodialysis. Serum levels of thyroid hormone and atrial natriuretic peptide (hANP) were measured. Body composition parameters were measured using a bioimpedance body composition analyzer.
Serum fT3 had positive correlations with body mass index (BMI), body fat mass (BFM), total body water (TBW) and intracellular water (ICW), and negative correlations with the ratio of extracellular water to total body water (ECW/TBW) and hANP. There were no correlations between serum fT4 and any body composition parameter. The 49 patients with data at baseline and after 1 year were divided into groups with increased (n = 33) and decreased (n = 16) fT3 after 1 year. ΔBMI and ΔBFM were significantly lower and ΔTBW, ΔICW, ΔECW and ΔECW/TBW (changes over 1 year from baseline) were significantly higher in patients with decreased fT3 compared to those with increased fT3. There was no significant difference in ΔhANP or Δcardiothoracic ratio between the two groups.
These results show that a decrease in fT3 might be associated with emaciation and interstitial edema in Japanese hemodialysis patients.
No preview · Article · Jun 2012 · Clinical and Experimental Nephrology
[Show abstract][Hide abstract] ABSTRACT: We describe a 41-year old man with obsessive-compulsive neurosis who developed acute renal failure (ARF) due to acute interstitial nephritis (AIN) during 6 weeks of treatment with clomipramine hydrochloride (CPH). He had a slight fever, mild arthralgia, appetite loss, and diarrhea after taking CPH. On admission, he showed serum creatinine (sCr) of 7.31 mg/dl, and creatinine clearance (Ccr) of 2.5 ml/min. He subsequently became anuric and required hemodialysis. Renal biopsy revealed AIN with diffuse mononuclear cell infiltration. After the withdrawal of CPH and treatment with prednisolone (PSL) 0.5 mg/kg per day, his urinary output improved, along with improvement of his renal function; therefore hemodialysis was finally discontinued. To our knowledge, this is the first case report of AIN induced by clomipramine.
No preview · Article · Oct 2007 · Clinical and Experimental Nephrology
[Show abstract][Hide abstract] ABSTRACT: A novel recombinant human hepatic cell line, CYP3A4- and glutamine synthetase (GS, an enzyme which converts ammonium ion and glutamate to glutamine)-introduced HepG2 (HepG2-GS-CYP3A4), was established. Its usefulness in a large-scale culture with a circulatory bioreactor in vitro and in dog models of ischemic hepatic failure with acute diazepam (DZP, a substrate of CYP3A4) overdosage was further examined. HepG2-GS-CYP3A4 expressed about 9 times larger amounts of CYP3A4 protein than a control. After incubation with HepG2-GS-3A4 cells in a circulatory bioreactor for 24 h, ammonia and DZP concentrations in the culture medium significantly decreased by about 40%. Furthermore, this system improved the survival time and decreased serum concentrations of DZP, ammonia, and transaminase in dogs with ischemic hepatic failure plus acute DZP overdosage. The mean survival time with bioreactor with HepG2-GS-3A4 was 42.7 +/- 3.6 h, which was significantly longer than that without reactor, with reactor (no cells), and with HepG2-GS (23.4 +/- 2.8, 22.1 +/- 2.4, and 31 +/- 3.7 h, respectively). Therefore, it is concluded that this bioartificial liver could be a good tool for the treatment of dogs with hepatic failure and that it could potentially be a bridging procedure to liver transplantation.
No preview · Article · Sep 2005 · Artificial Organs
[Show abstract][Hide abstract] ABSTRACT: To compare the degree of taste disturbance by candesartan and valsartan.
Candesartan cilexetil (4 mg day(-1)), valsartan (40 mg day(-1)), or vehicle was given to subjects (n = 8) for 13 days in a randomized, placebo-controlled, three-way crossover design with a 14-days washout period. Gustometry by filter-paper test and electrogustometry were performed before and at the end of each trial. Plasma renin activity and zinc concentrations in serum and saliva were measured.
Detection thresholds of four basic tastes (sweet, salty, sour and bitter) by paper-disc test and electrogustometry were significantly worsened and plasma renin activity was elevated after the test, while the effects of two drugs did not significantly differ. These drugs did not affect zinc concentrations.
Both candesartan and valsartan similarly alter taste sensitivity after the repeated dosing of the drug.
Full-text · Article · Sep 2005 · British Journal of Clinical Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Cyclosporine A (CsA) causes distal renal tubular acidosis (RTA) and osteoporosis. We have recently reported that the reduction of nitric oxide (NO) exacerbates this condition. Distal RTA may deplete bone mineral due to the chronic buffering of acid in the blood. The interaction of CsA and NO in causing metabolic acidosis and bone demineralization has not been studied previously. Nor has the salubrious effect of citrate therapy.
To examine the effect of systemic pH correction by citrate on renal electrolyte (Na, K, Cl, NH3, HCO3) excretion following acute water loading in CsA-treated and NO-reduced rats. We further evaluated femoral bone density and bone demineralization activity after the same treatments.
Rats received CsA, L-arginine (L-Arg), or nitro-L-arginine-methyl ester (L-NAME), or a combination of CsA+L-NAME plus or minus citrate. Urine and blood electrolytes were examined, as well as the urine excretion of deoxypyridinoline and the bone density of both femurs.
CsA and L-NAME reduced urine pH and the serum HCO3- concentration, and increased serum K+ and Cl- concentrations. The combination of CsA with L-NAME caused more severe deficits in the serum HCO3- concentration and elevations in serum K+ and Cl- concentrations than either drug alone. Both CsA and L-NAME reduced urinary nitrate excretion, which was reversed by co-administration of L-Arg. Co-administration of citrate or L-Arg improved the CsA- and L-NAME-induced acidosis and hyperkalemia. Bone resorption and density of the femurs were decreased by CsA and L-NAME and were additive for both drugs. Co-administration of citrate or L-Arg restored both bone resorption and density to normal levels.
CsA induces a hyperchloremic metabolic acidosis with hyperkalemia and a reduction in NO. The ensuing systemic acidosis causes bone resorption and demineralization. These effects were corrected by co-treatment with citrate. Citrate, at least in part, directly reduces the protonation of bone in animals treated with CsA and is recommended as a potential adjunct drug to prevent bone demineralization in patients chronically receiving CsA.
No preview · Article · May 2005 · American Journal of Nephrology
[Show abstract][Hide abstract] ABSTRACT: The nuclear receptors liver X receptor (LXR) alpha and farnesoid X receptor (FXR) are positive and negative regulators of cholesterol 7alpha-hydroxylase (CYP7A1) transcription, respectively. To clarify their roles in the regulation of CYP7A1 in mice, we investigated mRNA expression of their target genes in the livers of C57BL/6 mice fed the following five diets for 2 weeks: a standard diet, cholic acid, cholesterol, cholesterol+high fat, or an atherogenic diet (cholic acid+cholesterol+high fat). The mRNA level of ATP-binding cassette transporter (ABC) A1 gene, one of LXRalpha target genes, significantly increased on the diets containing cholic acid and/or cholesterol+high fat, but not on the diet containing cholesterol alone. On the other hand, the mRNA levels of the FXR target genes ABCB11, ABCC2, and short heterodimer partner increased only on the diet containing cholic acid with or without cholesterol+high fat. Surprisingly, cholesterol alone or cholesterol+high fat did not affect CYP7A1 mRNA level, whereas cholic acid with or without cholesterol+high fat greatly reduced the level. Thus, in the atherogenic diet-fed mice, cholic acid component is needed for the FXR activation, and FXR dominantly regulates CYP7A1 transcription.
[Show abstract][Hide abstract] ABSTRACT: This study was undertaken to evaluate removal of 22-oxacalcitriol (OCT), an active and intravenously used vitamin D3 analogue with less calcaemic activity, by polysulphone haemodialyser in vivo and in vitro. We further compared the pharmacodynamic efficacy [suppression of intact parathyroid hormone (iPTH)] when given intravenously either during or at the end of the haemodialysis.
(i) Drug clearance by the polysulphone dialyser was measured during a single continuous infusion (5 microg) for 30 min into the arterial side of the dialyser in end-stage renal failure patients with secondary hyperparathyroidism (n = 7). (ii) The drug adsorption by the hollowfibre membrane during incubation for 30 min was measured in vitro. (iii) To evaluate efficacy, the drug was given (i.v. bolus) during or at the end of haemodialysis for 4 weeks in a cross-over fashion with a washout period of 8 weeks (n = 9). Serum Ca(2+), phosphate (P) and iPTH concentrations just before the initiation of the dialysis were monitored every week.
(i) OCT was significantly cleared by the polysulphone haemodialyser, but the clearance declined in a time-dependent manner to approach zero at 30 min. Arterial (at the place between the drug infusion site and the haemodialyser column) drug concentrations did not change during the infusion (mean = 2064 +/- 233 pg ml(-1)). Venous (just after the dialyser) drug concentrations at 10 min after the infusion were significantly lower than those of the arterial side (mean = 784 +/- 84 pg ml(-1)); however, they increased with time and reached those of the arterial side at 30 min. (ii) In vitro, OCT was adsorbed by the membrane. The amount of adsorption was concentration-dependent and was lower in the presence of human serum (55 +/- 4% without and 23 +/- 4% with serum at 600 pg ml(-1) of OCT). (iii) Although serum Ca(2+) and P increased and iPTH decreased by both treatment regimens (i.e. OCT administered either during or at the end of haemodialysis), these changes did not significantly differ. Mean differences (and 95% confidence interval) of Ca(2+), P, and iPTH at the end of the trial were 0.03 (-0.04, 0.09) mm, 0.41 (-0.43, 1.26) mg dl(-1) and 38 (-42, 88) pg ml(-1), respectively.
OCT is adsorbed by polysulphone dialyser in vitro and in vivo. However, the pharmacodynamic effectiveness was largely independent of the administration regimen of OCT given either during or at the end of haemodialysis.
Full-text · Article · Dec 2004 · British Journal of Clinical Pharmacology
[Show abstract][Hide abstract] ABSTRACT: In vitro inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase causes the suppression of liver X receptor (LXR) activity. Because LXR regulates the expression of ATP-binding cassette transporter (ABC) A1, which is involved in the high-density lipoprotein-related reverse cholesterol transport pathway, we examined the effects of an HMG-CoA reductase inhibitor pravastatin on ABCA1 expression in vitro and in vivo. Pravastatin (10 microM) significantly reduced the transcript levels of murine ABCA1 gene by 35% in RAW264.7 macrophages under a lipoprotein-deficient condition. The inhibition was due to the decreased mevalonic acid production because addition of exogenous mevalonic acid restored ABCA1 mRNA levels. In addition, cholesterol and 22(R)-hydroxycholesterol thoroughly blunted the inhibition. Furthermore, pravastatin did not decrease ABCA1 mRNA and protein levels in HepG2 hepatocytes even in the absence of exogenous LXR agonists. Oral dosing of pravastatin (0.1% concentration in drinking water) for 24 h or 2 weeks to mice did not decrease ABCA1 mRNA and protein levels in the liver and leukocytes. Interestingly, pravastatin significantly increased both hepatic and leukocyte LXRalpha mRNA levels. Thus, although HMG-CoA reductase inhibitors suppress ABCA1 mRNA expression in the absence of LXR agonists, in vivo inhibition of HMG-CoA reductase is unlikely to cause such suppression.
Preview · Article · Nov 2004 · Journal of Pharmacology and Experimental Therapeutics
[Show abstract][Hide abstract] ABSTRACT: Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat.
GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR).
Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis.
These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.
Full-text · Article · Oct 2004 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: We have previously reported that a beta2-microglobulin adsorption column for the treatment of dialysis-related amyloidosis decreased serum digoxin concentration in renal failure patients. Because the distribution volume of digoxin is high, it is uncertain whether the repetitive use of this column influences the pharmacokinetics of digoxin in renal failure patients. We have observed 3 renal failure patients whose trough serum digoxin concentrations were significantly reduced by the repetitive use of tandem beta2-microglobulin adsorption columns for treatment of dialysis-related amyloidosis. These patients experienced symptomatic elevation of their heart rates in parallel with a significant reduction in serum digoxin concentrations. Termination of the use of the adsorption column improved the symptoms in 1 patient; however, severe arthritic pain caused by amyloidosis relapsed. Dosage of digoxin was increased in 2 other patients with continuous treatment by the column. Their digoxin concentrations increased, and their heart rates decreased without any deterioration of joint pain. We have demonstrated that the repetitive use of the beta2-microglobulin adsorption column in tandem with standard hemodialysis actually decreases trough digoxin concentration in renal failure patients. Careful monitoring and alteration of digoxin dosage regimens are needed under these circumstances.
No preview · Article · Sep 2004 · Therapeutic Drug Monitoring
[Show abstract][Hide abstract] ABSTRACT: MC (mesangial cell) proliferation is closely linked to the progression of glomerular disease. It has been reported that cAMP effectors suppress MC proliferation, inhibiting activation of MAPK (mitogen-activated protein kinase). In fibroblasts, activation of MAPK induces the expression of type D cyclin, whereas, in MCs, this induction has not been shown. In the present study, we explored the effects of cAMP on MAPK and expression of cell-cycle-regulated proteins. PDGF (platelet-derived growth factor) stimulated MAPK activity, up-regulated protein levels of cyclin D1, CDK2 (cyclin-dependent kinase 2) and PCNA (proliferating cell nuclear antigen), decreased the protein level of p27 and increased DNA synthesis. Fsk (forskolin) or PD98059 suppressed PDGF-induced DNA synthesis. Both agents inhibited PDGF-stimulated mRNA and protein expression of cyclin D1 and CDK2. Fsk or PD98059 also inhibited protein expression of PCNA and blocked a decrease in p27 protein. Fsk induced the phosphorylation of Raf-1 at Ser259, which was inhibited by KT5720. These data suggest that cAMP inhibits MC proliferation through inhibition of MAPK activity, and this mechanism partly involves alteration in the levels of cell-cycle-regulated proteins.
[Show abstract][Hide abstract] ABSTRACT: We have previously reported the merits of chronopharmacological effect of 1-alpha(OH) vitamin D3 in aged stroke-prone spontaneously hypertensive rat (SHRSP), a model of osteoporosis [Eur. J. Pharmacol. 428 (2001) 283.]. In this study, the chronopharmacological effect of 22-oxacalcitriol, a newly developed active vitamin D3 analogue with less calcemic activity, was evaluated by a single and repeated dosing of the drug in aged SHRSP. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Single (12.5 microg/kg, i.v.) and repeated (5 microg/kg, i.v. three times a week for 12 weeks) dosing of 22-oxacalcitriol or vehicle was given at either 2 h after lights on (2HALO) or 14 h after lights on (14HALO). The severity of adverse reactions such as the changes of body weight, hypercalcemia and hyperphosphatemia, was significantly mild when the drug was given at 14HALO. Especially, the increase of serum Ca concentration was not detected at 14HALO trial. Serum concentrations of total (protein-bound and unbound) 22-oxacalcitriol and albumin (a major binding protein of the drug) of the 2HALO and 14HALO trials did not significantly differ. The decrease of parathyroid hormone (PTH) concentration was greater in the 14HALO trial while the increase in urinary ratio of Ca to creatinine was greater in the 2HALO trial. The increase in bone density of both femurs at the end of the study was greater in the 14HALO trial. The suppression of urinary excretion of deoxypyridinoline, an index of bone resorption capacity of osteoclast, was greater in the 14HALO trial, which indicates that the efficacy of 22-oxacalcitriol for suppressing bone resorption might vary with the dosing time. This is the first study to show the dosing-time-dependent changes in the efficacy and toxicity of 22-oxacalcitriol in the animal model of osteoporosis. Chronopharmacological differences seem to be more prominent than those of other vitamin D analogues. To use 22-oxacalcitriol at an adequate timing might provide better efficacy and safety than other vitamin D3 analogues for the treatment of osteoporosis.
No preview · Article · Apr 2004 · European Journal of Pharmacology