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Biomedical subjects

M T Houser

Publications and source records attributed to M T Houser.

At least 19 recordsLinked to original sources
PubMed1994

Synergistic effects of fish oil diet and dimethylthiourea in acute adriamycin nephrosis.

The synergistic effects of combining fish oil (FO) diet, which reduces thromboxane A production, with the free radical scavenger, dimethylthiourea (DMTU), were evaluated in acute adriamycin nephrosis, because proteinuria in adriamycin nephrosis is mediated by increased renal thromboxane A and free radical production. The effects of combined evening primrose oil (EPO) and DMTU were compared with the DMTU + FO combination because EPO increases prostaglandin E but not thromboxane A. After 7, 14, and 21 days, proteinuria was significantly (p < 0.05) reduced in rats receiving either DMTU + corn oil (CO) or DMTU + FO compared with untreated control rats. However, after 21 days, rats receiving DMTU + FO had significantly reduced urine protein excretion compared with those receiving DMTU + CO (103.9 +/- 20 mg daily vs 351.8 +/- 29.8 mg daily; P < 0.05). In contrast to FO, rats receiving EPO + DMTU had similar urine protein excretion to rats receiving DMTU + CO after 21 days (170.2 +/- 20.34 mg daily vs 179.45 +/- 26.38 mg daily). The mean serum cholesterol concentration was significantly (P < 0.01) reduced in rats receiving DMTU + FO (195.2 +/- 23.8 mg/dL) compared with DMTU + CO (377.9 +/- 28.5 mg/dL). Serum triglyceride levels also were significantly (P < 0.01) reduced in rats receiving DMTU + FO (52.5 +/- 26.4 mg/dL) compared with DMTU + CO (100.5 +/- 36.9 mg/dL). No significant differences in serum cholesterol concentrations or triglycerides occurred between rats receiving DMTU + CO and DMTU + EPO. Renal glutathione content was significantly (P < 0.05) increased by 23% in normal rats receiving FO diet and by 34% in rats receiving combined DMTU + FO compared with CO alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Glomerular injury in end-stage liver disease--role of circulating IgG and IgM immune complexes.

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.

Antigen-Antibody Complex↗
PubMed1993

Enhancement of renal and hepatic glutathione metabolism by dimethylthiourea.

Dimethylthiourea (DMTU), a free radical scavenger, was administered to rats to study its effect on renal and hepatic glutathione metabolism, since it is a potential sulfhydryl donor. Six hours following DMTU, renal GSH content was significantly (P < 0.05) increased (10%), and was increased further after 24 h (28%) (P < 0.001). Hepatic GSH content was also significantly (P < 0.001) elevated at 6 and 24 h (5 and 33%, respectively). Seven days of daily DMTU therapy significantly (P < 0.001) increased renal and hepatic GSH content by 36 and 54%, respectively, which was associated with a significant (P < 0.001) increase in the renal activities of glutathione peroxidase (GP) by 38%, glutathione transferase (GT) by 92%, and glutathione reductase (GR) by 19% (P < 0.05). Significantly increased activities of hepatic GP by 84% (P < 0.01) and GT by 101% (P < 0.001) also occurred in DMTU-treated rats after 7 days of continuous therapy. From these data, we conclude that DMTU stimulates renal and hepatic GSH metabolism, which may be important in mediating DMTU's protective effect against free radical-induced tissue injury.

Animals↗
PubMed1992

Glutathione monoethyl ester moderates mercuric chloride-induced acute renal failure.

Glutathione (GSH)-dependent reactions are an important cellular defense against ischemic or oxidative injury, although their role in toxin-induced renal cellular injury is less clear. Because of the known sulfhydryl reactivity of mercury (M), we hypothesized that GSH could modify mercuric chloride (MC)-induced acute renal failure (ARF). Therefore, we evaluated the effects of glutathione monoethyl ester (GE), which produces high intrarenal levels of GSH, on the nephrotoxicity of MC. GE treatment in normal rats did not alter their creatinine clearance (CCr), fractional sodium (CNa/CCr) or lysozyme (CLy/CCr) excretion, but histologically resulted in prominent proximal tubular vacuolization. GE pretreatment in rats with MC-induced ARF resulted in partial preservation of their CCr, CNa/CCr and CLy/CCr. Renal histology also demonstrated a reduction in tubular necrosis. M content in the renal cortex 3 following MC was lower in the MC + GE group, but levels were higher in the liver and inner stripe/inner medulla as compared to animals receiving MC alone. No differences were seen in the outer stripe at 3 h or in any of the tissues 24 h following MC injection. Thus, GE moderated MC-induced ARF, likely by providing a large intracellular sulfhydryl pool and thereby reducing M reactivity with endogenous cellular proteins and enzymes.

Acute Kidney Injury↗
PubMed1992

Role of glutathione metabolism in the reduction of proteinuria by dimethylthiourea in adriamycin nephrosis.

Glutathione (GSH) metabolism, a tissue detoxification pathway, was evaluated in rats with adriamycin nephrosis (AN) treated with dimethylthiourea (DMTU), a free radical scavenger. After 7 days of DMTU, a significant reduction in proteinuria occurred as compared to AN controls (62.4 +/- 13.3 vs. 155.0 +/- 24.0 mg/24 h). A significant increase in renal cortical GSH content as well as glutathione peroxidase (GP) and transferase (GT) activities occurred in DMTU-treated rats as compared to controls. Glutathione monoethyl ester (GME) administration alone reduced proteinuria by 21% in AN, which was not significant despite a large increase in the renal GSH content, however, GP and GT activities were not increased by GME. We conclude that DMTU ameliorates glomerular injury in AN by stimulating GSH metabolism.

Animals↗
PubMed1991

Renal tubular protein handling in experimental renal disease.

Competitive inhibition of renal tubular transport occurs between low- and high-molecular-weight proteins following intravenous infusion, but this relationship is less clear following de novo glomerular or renal tubular injury. The present study evaluated renal lysozyme and albumin handling following renal tubular injury induced by both low- and high-dose mercuric chloride (0.5 and 2.0 mg/kg) and maleic acid (50 and 400 mg/kg), and following glomerular injury induced by puromycin aminonucleoside (5 mg/100 g) or Adriamycin (5 mg/kg). Subtle renal tubular injury induced only mild isolated albuminuria, while severe tubular injury caused dramatic lysozymuria and moderate albuminuria. However, increased filtration of albumin in these models of glomerular injury did not inhibit lysozyme transport.

Albumins↗
PubMed1991

Amelioration of glomerular injury in doxorubicin hydrochloride nephrosis by dimethylthiourea.

The hydroxyl radical scavengers dimethylthiourea (DMTU), sodium benzoate, and dimethylsulfoxide (DMSO) were administered to rats before doxorubicin hydrochloride (ADR) (5 mg/kg, IV) to probe the role of free radicals in mediating proteinuria in doxorubicin hydrochloride nephrosis (AN). Because ADR stimulates free radical production, the role of renal glutathione was also evaluated; glutathione metabolism is involved in tissue detoxification processes. DMTU administration to rats with AN caused a significant (p less than 0.01) reduction in their proteinuria after 7 days (52.84 +/- 13.21 mg/24 hours) when they were compared with ADR controls (155.81 +/- 20.16 mg/24 hours). In similar fashion, their urine albumin excretion was also significantly reduced when compared with that of ADR controls (11.13 +/- 2.75 mg/24 hours vs 32.08 +/- 4.14 mg/24 hours; p less than 0.01). DMTU-treated rats also had significantly (p less than 0.001) reduced urinary protein and albumin excretion at 14 days when compared with rats that received ADR alone. The urinary excretion of lysozyme and N-acetyl-glucosaminidase, markers of renal tubular injury, were significantly increased after 7 or 14 days in rats with AN, despite DMTU treatment. Creatinine clearance was significantly reduced (p less than 0.05) in rats receiving ADR alone (0.223 +/- 0.011 ml/min/100 gm) when compared with that in normal controls (0.331 +/- 0.027 ml/min/100 gm) or DMTU-treated rats (0.289 +/- 0.035 ml/min/100 gm). Unlike DMTU, neither sodium benzoate nor DMSO reduced proteinuria in rats with AN.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1988

Unilateral nephrectomy in the rat: effects on mercury handling and renal cortical subcellular distribution.

As unilateral nephrectomy (UNX) is associated with enhanced mercuric chloride nephrotoxicity, studies were undertaken to characterize the effects of UNX on the tissue content, urinary excretion, and renal cortical subcellular distribution of mercury in the rat. Animals were studied immediately, 2 days or 14 days following UNX, during separate phases of compensatory renal hypertrophy. As compared to sham surgery controls, mercury content in renal cortex was higher in all UNX groups at 24 hr following injection and in the immediate and 2-day groups at 1 or 3 hr. However, UNX was not associated with any alteration in mercury content within outer or inner medulla, liver, plasma, or red blood cells. Subcellular distribution studies demonstrated that cytosolic mercury was uniformly elevated in all UNX groups at 1, 3, and 24 hr following injection while mercury bound to "metallothionein-like" proteins or free in the cytosol was increased only at 1 or 3 hr. Nuclear, mitochondrial, or microsomal mercury content was elevated in the animals studied immediately or 14 days after UNX at 3 or 24 hr following injection, while animals studied 2 days after UNX demonstrated a nearly uniform increase at 1, 3, and 24 hr. Single-kidney urinary mercury excretion was elevated in all UNX groups while excretion per gram kidney weight was increased only in the animals studied immediately or 2 days after surgery. These studies suggest that all phases of compensatory renal hypertrophy are associated with an enhanced content of mercury within the cell cytoplasm and in critical cellular organelles, which may explain the enhanced nephrotoxicity seen following UNX.

Animals↗
PubMed1987

Characterization of recumbent, ambulatory, and postexercise proteinuria in the adolescent.

To better characterize the effects of body position and exercise on urinary protein excretion, carefully defined random urine samples were obtained during recumbency and following both ambulation and exercise in healthy adolescent student athletes. Albumin, lysozyme, and N-acetyl-B-D-glucosaminidase were measured in all samples. Glomerular permeability and tubular function were assessed using the urinary albumin creatinine ratio (UAlb/UCr), the urinary lysozyme creatinine ratio (ULy/UCr), the urinary N-acetyl-B-D-glucosaminidase creatinine ratio (UNag/UCr), and the urinary lysozyme albumin ratio (ULy/UAlb). UAlb/UCr was significantly (p less than 0.001) lower in recumbent urine samples than in either ambulatory or postexercise samples, although no difference was seen between the latter two groups. Furthermore, recumbent UAlb/UCr was higher in females (p less than 0.01) and postexercise UAlb/UCr varied significantly (p less than 0.001), depending on the type of physical activity. ULy/UCr, UNag/UCr, and ULy/UAlb were unaffected by either posture or physical activity. A significant correlation was found between UAlb/UCr and UNag/UCr (r = 0.60, p = 0.0001) and also between ULy/UCr and ULy/UAlb (r = 0.84, p = 0.001). In addition, urine-specific gravity was found to have a significant negative correlation with UAlb/UCr (r = -0.33, p = 0.001). The results of this study suggest that in the adolescent, recumbent albumin excretion is higher in females and that ambulation increases glomerular permeability. Exercise does not appear to induce any additional alteration in glomerular permeability, although the effects of exercise are likely-related to the type and severity of physical activity. Renal tubular function is unaltered by either ambulation or exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1986

The effect of unilateral nephrectomy on the nephrotoxicity of mercuric chloride in the rat.

Unilateral nephrectomy (UNX) induces a dramatic change in single-kidney structure and function. Therefore, the effects of nephrotoxins may be altered. To evaluate this possibility, mercuric chloride (2 mg/kg, sc) was given to male, Sprague-Dawley rats 2 days following either UNX or sham surgery. Nonoliguric acute renal failure developed and was qualitatively similar in both groups. Glomerular filtration rate (GFR) reached a nadir on Day 2 and was reduced to a greater extent in the UNX group. Furthermore, recovery of GFR was slower and occurred to a lesser extent by Day 10 in the animals subjected to UNX. Evidence of significant tubular dysfunction was present during the acute phase in both groups, as reflected by changes in the fractional excretion of sodium or lysozyme. Persistent tubular dysfunction was noted on Day 10 in both the sham and UNX groups, but the degree of dysfunction was greater in the UNX animals. The in vitro uptake of organic ions by renal cortical slices was reduced 24 hr following the injection of mercuric chloride although no difference was seen between the experimental groups. Mercury content within renal cortex was not increased in the UNX group at 1 or 3 hr but was higher 24 hr postinjection. Total urinary mercury excretion during the first day was not altered by UNX although single-kidney excretion was increased dramatically. These studies suggest that rats are more susceptible to mercuric chloride-induced nephrotoxicity 2 days following UNX. Although the mechanism(s) of this enhanced injury remains unclear, it does not appear to be completely related to an increase in renal cortical mercury content.

Acute Kidney Injury↗
PubMed1986

Assessment of urinary protein excretion in the adolescent: effect of body position and exercise.

We examined the effects of body position and exercise on the random urinary protein/creatinine ratio (Up/Ucr) in healthy adolescents, to provide reference data to be used in a simplified evaluation of proteinuria. Random urine samples were obtained during recumbency and after both ambulation and exercise in 116 subjects. The Up/Ucr was significantly (P less than 0.0001) higher with increasing levels of activity, and was widely variable, especially during the upright and postexercise periods. No sex-related differences in Up/Ucr were noted, except during recumbency, when values were significantly (P less than 0.001) higher in females. The urinary dipstick was found to be less sensitive as a tool to define abnormal degrees of recumbent proteinuria. We conclude that body position and exercise have significant effects on protein excretion, and suggest that the Up/Ucr in recumbent and upright urine samples will be useful in the evaluation of proteinuria.

Adolescent↗
PubMed1986

The effects of age and urine concentration on lysozyme and N-acetyl-beta-D-glucosaminidase (NAG) content in urine.

Random urine samples were obtained to evaluate potential age- or urine concentration-related differences in lysozyme or NAG content. The concentration and excretion of both enzymes was widely variable although no age-related differences were seen. Urine concentration, however, was an important variable as NAG concentration (per mL urine) and lysozyme excretion (per mumol creatinine) were significantly elevated and reduced, respectively, in samples with a higher specific gravity. The correlation coefficient between urine specific gravity and both parameters was significant. Lysozyme excretion is elevated in subjects undergoing a modest diuresis although NAG excretion is unaffected. These data may prove to be useful in the evaluation of renal dysfunction.

Acetylglucosaminidase↗
PubMed1986

The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man.

To substantiate the effects of urine flow rate on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase (NAG) excretion, experiments were performed in normal human subjects. Urine flow rate was varied by overnight fluid deprivation and progressive diuresis induced by oral water loading. Lysozyme measurements were made using an improved turbidimetric method and NAG determinations using a modified fluorometric assay utilising individual recovery techniques. Fractional lysozyme clearance and lysozyme excretion demonstrated a nearly linear relationship with urine flow rate (r = 0.78, r = 0.80, P less than 0.0005), and both were elevated significantly in samples obtained during diuresis. NAG excretion, however, demonstrated a significant but weak correlation (r = 0.47, P less than 0.005) with fractional urine flow rate. A significant (P less than 0.05) difference in NAG activity occurred only during the period of hydropenia, when a decrease in excretion was observed. These findings suggest that the effect of diuresis on lysozyme excretion should be considered in studies utilising this enzyme as a marker of renal injury.

Acetylglucosaminidase↗
PubMed1983

Improved turbidimetric assay for lysozyme in urine.

I describe an improved turbidimetric assay for lysozyme in urine. This method is simple, reproducible, linear over a 100-fold concentration range, sensitive to concentrations as low as 10 micrograms/L, and only commercially available products are required. Evaluation of urinary lysozyme concentration with this assay demonstrated a within-run and between-run CV of 9.9% and 4.8%, respectively, for normal urine, minimal chemical interference, and a mean analytical recovery of 104.8%. There were differences in the rate of clearing and in the linearity of the assay with use of three commercial preparations of Micrococcus lysodeikticus, and significant differences in results when different lysozyme standards were used. Reference values were established by use of data on 169 healthy subjects, ages six months to 61 years. Clinical efficacy of the assay was demonstrated in children with renal disorders, especially those associated with chronic renal failure or tubular dysfunction.

Adolescent↗
PubMed1982

Preservation of mesangium and immunohistochemically defined antigens in glomerular basement membrane isolated by detergent extraction.

To define the characteristics of isolated glomerular basement membrane (GBM), immunohistochemical and morphometric analyses have been carried out on rat and human tissues. Site-specific arrays of antigens were identified in detergent-isolated GBM in a distribution similar to that observed in intact kidney. In the human, fibronectin, procollagen IV, and collagen V were observed along the internal aspect of GBM continuous with antigenic sites in the mesangium. Another array of antigens was identified in the GBM but not within the mesangium--Goodpasture's antigen, bovine lens capsule type IV collagen, and amyloid P component. In addition, sites reactive with rabbit antiserum to laminin were present on both sides of the lamina densa as well as within the mesangial region. Actomyosin, a presumed mesangial cell antigen persisted in the mesangium of isolated GBM. Mesangial matrix was identified in detergent-isolated GBM in an amount equivalent to that present in intact glomeruli. Sonicated GBM contained the same antigens but it was not possible to quantitate the amount of mesangial material by immunofluorescence or morphometric analysis. The thickness of the lamina densa was greater in sonicated and detergent-treated rat GBM preparations than in native rat kidney. These studies demonstrated that isolated GBM is heterogeneous with respect to its antigenic constituents and in addition contains mesangial matrix, which is morphologically and immunohistochemically distinct from peripheral GBM.

Actomyosin↗
PubMed1982

Candida peritonitis in children on continuous ambulatory peritoneal dialysis.

The management, complications and outcome of two small children who developed Candida albicans peritonitis are reported. Both children developed peritonitis while on continuous ambulatory peritoneal dialysis (CAPD) but their fungal infections were treated differently. In one patient, Amphotericin B (1-4 micrograms/ml) was added to the dialysate; infection resolved but an extensive fibrous reaction developed in the peritoneal cavity making subsequent CAPD ineffective. The second patient was treated with a recently introduced oral antifungal agent, Ketoconazole; her catheter was removed. This patient recovered without any identifiable side effects of the drug. This report discusses the clinical course of two different approaches to Candida peritonitis and suggests certain recommendations regarding the treatment of this uncommon, but potentially lethal complication of CAPD.

Amphotericin B↗
PubMed1981

Renal failure as a complication of acute antihypertensive therapy.

Adult patients with long-standing hypertension have been reported to experience an impairment in renal function when treatment with potent vasodilating agents is initiated. To document that this sequence may occur in children as well, we report the case of a 4-year-old boy with renal disease in whom reduction of blood pressure to normal levels was accompanied on three occasions by oliguric renal failure. During each episode, the correlation between reduction in blood pressure and increase in serum creatinine level was significant (P less than .05); furthermore, the slope of the relationship was similar with each episode. This phenomenon suggests an impairment of renal autoregulation in this patient. Maintenance of normal blood pressure for several months was accompanied by a gradual return of renal function to pretreatment levels. This case suggests that particular attention should be paid to renal function during the initiation of antihypertensive therapy, particularly in patients with renal vascular damage. Present evidence does not appear to warrant modification of the current therapeutic philosophy of aggressive management in patients with severe hypertension.

Acute Kidney Injury↗