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Biomedical subjects

R M Weiss

Publications and source records attributed to R M Weiss.

At least 55 records · Page 3Linked to original sources

Effect of long-term oral L-arginine on the nitric oxide synthase pathway in the urine from patients with interstitial cystitis.

PURPOSE: We attempted to determine whether oral L-arginine, the substrate for nitric oxide synthase, increases nitric oxide synthase activity and cyclic guanosine monophosphate (cGMP) levels in the urine from interstitial cystitis patients. Nitric oxide and cGMP are decreased in urine from interstitial cystitis patients and both induce smooth muscle relaxation and immunological responses. Increasing urinary nitric oxide and cGMP may ameliorate interstitial cystitis symptoms. MATERIALS AND METHODS: Eight patients with interstitial cystitis were given L-arginine (1,500 mg. a day) orally for 6 months. Before and during treatment nitric oxide synthase activity and inducible nitric oxide synthase protein, cGMP, nitrate plus nitrite and interleukin 8 (IL-8) levels were measured in urine. RESULTS: After 2 weeks to 1 month of oral L-arginine treatment, urinary levels of nitric oxide synthase related enzymes and products increased significantly, while levels of the cytokine IL-8 were not changed significantly. IL-8 was significantly elevated in interstitial cystitis patients with leukocyte esterase positive urine. CONCLUSIONS: Long-term oral administration of L-arginine increases nitric oxide related enzymes and metabolites in the urine of patients with interstitial cystitis, which is associated with a decrease in interstitial cystitis related symptoms.

Administration, Oral↗

Experimental diabetes upregulates the expression of uretereral endothelin receptors.

We investigated the binding characteristics of endothelin (ET) receptors in the ureters of rats with experimentally induced diabetes and diuresis. Receptor binding experiments demonstrated an upregulation in the expression of [125I]ET-1 binding sites in the diabetic rat ureter but not in the diuretic rat ureter. ET-1, ET-3, IRL 1620, and BQ 610 inhibited [125I]ET-binding to the rat ureter consistent with the predominance of ETA receptors in these tissues. The subtype specificity of ET receptors in ureteral tissues was confirmed with inhibition data obtained from cloned human ETA and ETB receptors.

Animals↗

Age-dependent changes in particulate and soluble guanylyl cyclase activities in urinary tract smooth muscle.

Regional and age specific differences are observed in the sodium nitroprusside induced relaxation responses in the urinary tract. To clarify these differences, guanylyl cyclase activity is assayed in particulate and soluble fractions from the ureter, bladder dome, and urethra of young (11-18 days), adult (90-100 days), and old adult (2-3 years) guinea pigs. The rank order of soluble guanylyl cyclase activities is urethra = ureter > bladder dome with the largest decreases with aging occurring in the bladder. Atrial natriuretic factor (10(7) M) increases particulate guanylyl cyclase activity in the three tissues at all ages tested, with the activity being highest in the ureter. ATP (0.5 mM) activates particulate guanylyl cyclase in the ureter, bladder and urethra of old adult guinea pigs, and enhances atrial natriuretic factor induced activation of particulate guanylyl cyclase in all tissues and at all ages tested. The higher levels of soluble guanylyl cyclase activity in the urethra and ureter compared to the bladder parallel sodium nitroprusside induced relaxation in these tissues.

Aging↗

Improvement in interstitial cystitis symptom scores during treatment with oral L-arginine.

PURPOSE: Urinary nitric oxide synthase activity is decreased in patients with interstitial cystitis. Since nitric oxide may be an important determinant of the symptoms and immunological responses associated with interstitial cystitis, patients with this disease were treated with oral L-arginine, the substrate for nitric oxide synthase. MATERIALS AND METHODS: Ten patients took 1.5 gm. L-arginine orally daily for 6 months. Interstitial cystitis symptoms were surveyed before and during the 6-month trial. RESULTS: Oral L-arginine treatment resulted in a significant decrease in urinary voiding discomfort, lower abdominal pain and vaginal/urethral pain. Urinary frequency during the day and night also significantly decreased. CONCLUSIONS: This self-controlled study provides evidence that long-term oral L-arginine improves interstitial cystitis related symptoms.

Adult↗

Muscarinic receptor subtypes and receptor-coupled phosphatidylinositol hydrolysis in rat bladder smooth muscle.

BACKGROUND: The purpose of this study was to evaluate the muscarinic receptor subtypes expressed in rat bladder smooth muscle and characterize the muscarinic receptor-coupled phosphatidylinositol (PI) hydrolysis in order to clarify the first step of bladder smooth muscle contraction. METHODS: Expressions of mRNAs of muscarinic receptor subtypes were examined by Northern blot analysis. Changes in the mass of inositol 1,4,5-trisphosphate (IP3) and the inhibitory effects of muscarinic subtype specific antagonists on PI hydrolysis were determined after carbachol stimulation. RESULTS: mRNAs of m2 and m3 genes, encoding M2 and M3 receptors, were expressed in rat bladder smooth muscle. Carbachol produced a rapid increase of IP3, which returned to the basal level within 30 seconds. 4-Diphenylacetoxyl-N-methylpiperidine methiodide (4-DAMP; M1 and M3 antagonist) strongly inhibited the PI hydrolysis, but methoctramine (M2 antagonist) partially inhibited it at 10(-4) mol/L. The IC50 value for atropine was 9.5 x 10(-9) mol/L, for pirenzepine 6.4 x 10(-6) mol/L, and for 4-DAMP 1.5 x 10(-7) mol/L. CONCLUSION: M2 and M3 receptors are expressed in rat urinary bladder. Only M3 receptor was involved in the production of IP3, which might induce the initial phase of contractile response in rat bladder smooth muscle after carbachol stimulation.

Animals↗

Evidence for the presence of regional differences in the subtype specificity of muscarinic receptors in rabbit lower urinary tract.

To elucidate the subtype specificity of muscarinic cholinergic receptors in mediating contractile responses in the lower urinary tract, we investigated contractile and biochemical properties of muscarinic receptors in bladder dome, bladder base and urethra of the rabbit. Isometric contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype selective muscarinic antagonists. Bladder dome, bladder base, and urethra demonstrate different characteristics in terms of efficacy and potency with respect to carbachol-induced contractile responses. Emax values are significantly larger and ED50 values are significantly smaller in bladder dome and bladder base than in urethra. Calculation of the pA2 values, the negative logarithm of the antagonist affinity constant (KB), for a series of muscarinic antagonists, i.e., atropine (nonselective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-DAMP (M1/M3 selective) indicate that the carbachol-induced contractile response in bladder dome and bladder base is mediated through the M3 receptor subtype whereas the carbachol-induced contractile response in urethra is probably mediated through the M1 and/or M3 and possibly M2 subtypes. Muscarinic cholinergic antagonists inhibit [3H]quinulidinyl benzilate binding to bladder dome, bladder base and urethra with the following rank order of affinities: atropine > 4-DAMP > methoctramine > pirenzepine. The binding data indicate the predominance of the M2 receptor subtype in all three regions.

Animals↗

Neurokinin induced inositol phosphate production in guinea pig bladder.

PURPOSE: To examine second messenger pathways involved in neurokinin induced bladder contractions. MATERIALS AND METHODS: Neurokinin induced changes in inositol phosphate production and in adenylyl cyclase activity are measured in the guinea pig bladder. RESULTS: Substance P, substance P methyl ester, neurokinin A, and neurokinin B each increase [3H]-inositol phosphate production in the guinea pig bladder. Substance P (10(-6) M) increases [3H]-inositol trisphosphate levels within 30 sec. Substance P and neurokinin A have an additive effect on inositol phosphate production, however substance P (10(-5) M) or neurokinin A (10(-5) M) induced inositol phosphate production is less than that induced by carbachol (10(-5) M). Neurokinin B and to a lesser extent neurokinin A inhibit forskolin-activated adenylyl cyclase activity. CONCLUSIONS: These data are compatible with neurokinin-induced inositol phosphate production being coupled to increases in contractile force of the guinea pig urinary bladder, however more than one second messenger pathway may be involved.

Adenylyl Cyclases↗

Ipsilateral pyeloureterostomy for managing lower pole reflux with associated ureteropelvic junction obstruction in duplex systems.

PURPOSE: In duplex renal systems with a normal upper pole collecting system, and a lower pole collecting system with reflux and ureteropelvic junction obstruction or a kink at the ureteropelvic junction (that is reflux with trapping), treatment must address reflux and obstruction. We reviewed the results of ipsilateral pyeloureterostomy as a single corrective procedure. MATERIALS AND METHODS: We retrospectively reviewed our experience with 10 children who had complete ureteral duplication with lower pole reflux (grades III to V) and associated lower pole ureteropelvic junction obstruction or a ureteral kink with trapping. All patients were treated with ipsilateral end-to-side pyeloureterostomy. Followup ranged from 1 to 14 years. RESULTS: All patients had a good postoperative result, there have been no immediate or long-term complications and no subsequent surgical procedure was needed. All patients had continued lower pole renal growth with good function, 9 had resolution or a marked decrease in pelvicaliceal dilatation and none had evidence of obstruction. CONCLUSIONS: Ipsilateral end-to-side pyeloureterostomy for treating reflux into the lower moiety of a duplicated collecting system with associated ureteropelvic junction obstruction or a kink appears to be a single, safe corrective procedure that simultaneously manages vesicoureteral reflux and relieves the proximal obstructive process.

Child↗

Laparoscopic evaluation and management of a child with ambiguous genitalia, ectopic spleen, and Meckel's diverticulum.

Laparoscopy may be helpful in the evaluation and management of the child with intersex. Laparoscopic excision of dysgenetic gonads may be necessary due to the increased risk of malignancy. Residual müllerian duct structures are removed to prevent symptomatic complications at puberty. We present the case of a laparoscopic evaluation and management of a 46XY child with ambiguous genitalia, as well as the laparoscopic management of two unrelated anomalies discovered at the time of surgery.

Disorders of Sex Development↗

The ultrasonographic differentiation of obstructive versus nonobstructive hydronephrosis in children: a multivariate scoring system.

PURPOSE: We identified sonographic prognosticators to aid in distinguishing obstructive from nonobstructive hydronephrosis in children. MATERIALS AND METHODS: Twelve sonographic variables were initially analyzed to determine significant associations between the variables and the presence of urinary tract obstruction as defined by diuretic radionuclide renography. The significant findings were subsequently subjected to logistic regression models to identify potential predictors for obstructive hydronephrosis. RESULTS: The 7 variables associated with a significantly higher risk of urinary tract obstruction were increased echogenicity, parenchymal rims 5 mm. or less, contralateral hypertrophy, resistive index ratio 1.10 or greater, resistive index difference with diuresis of 70% or greater, ureter diameter 10 mm. or greater and aperistaltic ureter. These variables were used for the development of a multivariate scoring system. CONCLUSIONS: The obstructive scoring system shows promise as a screening method for the sonographic differentiation of obstructive from nonobstructive hydronephrosis in children.

Adolescent↗

Characterization of endothelin receptors in streptozotocin-induced diabetic rat vas deferens.

As there is increasing evidence that diabetes induces changes in the plasma levels of endothelins (ETs) and in the properties of ET receptors in peripheral tissues, and as there are reports indicating the presence of significant amounts of ET receptors in mammalian vasa deferentia, we studied possible alterations in ET receptor characteristics in the vasa deferentia of the following groups of rats: 8 weeks diabetic (D8), 8 weeks age-matched control (C8), 16 weeks diabetic (D16), 16 weeks diabetic-insulin-treated (started 8 weeks after the onset of diabetes) (DI16), and 16 weeks age-matched control (C16). Diabetes was induced by the i.v. injection of 65 mg/kg streptozotocin (STZ). Diabetic rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria and had smaller vasa deferentia than control and diabetic-insulin-treated animals. Receptor binding experiments with [125I]ET-1 demonstrated that the densities of ET receptors in vasa deferentia from D8, C8, D16, DI16, and C16 animals were 377 +/- 11, 255 +/- 24, 315 +/- 18, 210 +/- 12, and 214 +/- 7 fmol/mg of protein, respectively. [125I]ET-1 binding to the ET receptors was inhibited by ET-1 (non-selective), BQ 610 (ETA selective), ET-3 (ETC selective), and IRL 1620 (ETB selective) with the following rank order of Ki values: ET-1 < BQ 610 < ET-3 < < IRL 1620. The pharmacological profile of the ET receptors was similar in all groups and was consistent with the predominance of the ETA receptor subtype in the rat vasa deferentia. Our data indicate that experimental diabetes up-regulates the density of ET receptors in the rat vasa deferentia and that the receptor up-regulation is reversed by insulin treatment.

Animals↗

Effect of experimental diabetes on rat prostate endothelin receptors.

We studied the properties of endothelin receptors in the prostate of 8-week streptozotocin-diabetic and control rats. The density of endothelin receptors, as determined by saturation experiments with [125I]endothelin-1, were 95.8 +/- 5.4 and 171.3 +/- 16.7 fmol/mg of protein in control and diabetic rat prostates, respectively. The pharmacological profile of the endothelin receptors was similar in both groups and was consistent with the predominance of the endothelin ETA receptor subtype in the prostate. Thus, the induction of diabetes upregulates the expression of endothelin receptors in the rat prostate, but does not alter the pharmacological profile of the receptors in these tissues.

Animals↗

Case presentation: a patient with von Willebrand disease with menorrhagia.

A 42-year-old woman who had two normal uncomplicated vaginal deliveries was seen for menorrhagia. Endocrine studies and ultrasonography had normal results. An elevated bleeding time and an activated partial thromboplastin time led to further hematologic testing. Final testing revealed abnormalities in the von Willebrand factor antigen, which led to a diagnosis of mild type I von Willebrand disease.

Adult↗

Nitric oxide synthase induction with renal transplant rejection or infection.

Nitric oxide (NO) is readily oxidized to nitrate and nitrite and NO activates guanylyl cyclase, increasing cyclic GMP levels. To determine if nitric oxide synthase (NOS) is present in urine collected daily from patients following renal transplantation, we evaluated NOS activity in the leukocyte-rich particulate fraction and measured nitrate, nitrite, and cyclic GMP levels in the supernatant fraction of the urine. Reverse transcriptase-PCR and cDNA sequencing confirmed the presence of inducible NOS (iNOS) in cells obtained from the urine of renal transplant patients with rejection. NOS activity was elevated significantly in renal transplant patients with rejection (6.40 +/- 1.47 pmol citrulline/min/mg protein) or with urinary tract infection (29.56 +/- 11.00 pmol citrulline/min/mg protein), when compared to post-renal transplantation patients without rejection or urinary tract infection (0.51 +/- 0.21 pmol citrulline/min/mg protein). Nitrate levels increased in renal transplant patients with rejection and nitrite levels increased in renal transplant patients with urinary tract infection (UTI). Cyclic GMP levels increased with both rejection and UTI. This study demonstrates the presence of NOS activity and inducible NOS-mRNA in cells isolated from the urine of patients undergoing renal allograft rejection.

Adult↗

Physiology and evaluation of ureteropelvic junction obstruction.

Ureteropelvic junction (UPJ) obstruction is not a single anatomic entity but rather a set of processes with multiple causes. In the obstructed system, histologic changes are apparent that have implications for healing. The role of crossing vessels In UPJ obstruction and its treatment is of growing interest. Various methods are available to assess the functional characteristics of the UPJ, of which the diuretic renogram, Whitaker perfusion test, and Doppler ultrasound resistive index may be the most useful. The treatment must be individualized according to the patient's symptoms, the status of renal function, and the potential complications of intervention.

Evaluation Studies as Topic↗

Urinary nitric oxide synthase activity and cyclic GMP levels are decreased with interstitial cystitis and increased with urinary tract infections.

PURPOSE: Since urinary nitric oxide synthase (NOS) activity correlates with certain disease process affecting the urinary tract and since nitric oxide increases cyclic GMP levels by activating guanylyl cyclase, urinary particulate NOS activity and cyclic GMP levels are evaluated in female patients with interstitial cystitis (IC) and compared with those from female controls and female patients with urinary tract infections (UTIs). MATERIALS AND METHODS: Urinary NOS activity is measured as the formation of [(14)C]-L-citrulline from [(14)C]-L-arginine, and urinary cyclic GMP levels are measured by an [(125)I]-radioimmunoassay. RESULTS: Female patients with IC have significantly less NOS activity in their urine pellet particulate fractions than female control females UTIs, 2.3 +/- 1.0, 14 +/- 3.0, and 120 +/- 10 pmol. citrulline formed/min./mg. protein. Urinary cyclic GMP levels are significantly lower in IC patients than in female controls or females with UTIs: 0.50 +/- 0.06, 0.82 +/- 0.14. and 3.72 +/- 0.81 micromol. cyclic GMP/g. creatinine. CONCLUSIONS: Regulation of urinary NOS activity with subsequent changes in nitric oxide and cyclic GMP may be an important determinant of symptoms and immunologic responses to UTIs and IC.

Adolescent↗

Enhancement of muscarinic receptor-coupled phosphatidyl inositol hydrolysis in diabetic bladder.

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrose-fed diuretic rat detrusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248:81, 1989; Diabetes 40: 265, 1991). To investigate the signal transduction pathway involved in this altered functional response, we examined muscarinic receptor-coupled phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuretic and age-matched control rat bladders. [3H]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphatidylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induced increase in inositol phosphate (IPs) production was higher in the diabetic bladder than in bladders from control and sucrose-fed animals although the EC50 values were similar for all groups. Enhanced inositol phosphate production after muscarinic agonist stimulation may be due not only to the upregulation of muscarinic receptors but also the increased incorporation of myo-inositol into PI in the STZ-induced diabetic bladder.

Animals↗