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Biomedical subjects

H Matzkin

Publications and source records attributed to H Matzkin.

At least 37 records · Page 2Linked to original sources

Cross talk between melatonin and TGFbeta1 in human benign prostate epithelial cells.

BACKGROUND: Epithelial cells from the human benign prostate express melatonin receptors which effect transient suppression of DNA synthesis and sustained attenuation of growth. The role of transforming growth factor-beta1 (TGFbeta1), which is produced in prostate epithelial cells and inhibits their growth, was examined in the action of melatonin. METHODS: The effects of melatonin and TGFbeta1 and their combination on (3)H-thymidine incorporation were assessed. The possibility that melatonin effected TGFbeta1 release from cells was studied. RESULTS: Incubation of the cells with TGFbeta1 resulted in a time- and dose-dependent inhibition of (3)H-thymidine incorporation into cells. Melatonin (10-500 pM) inhibited (3)H-thymidine incorporation, and its effects were attenuated at higher (1-10 nM) concentrations. In the presence of submaximal doses of TGFbeta1, the inhibitory effect of melatonin was maintained over the entire concentration range tested (10 pM-10 nM). The inhibition of (3)H-thymidine incorporation by TGFbeta1 was more pronounced in the absence of dihydrotestosterone (DHT) than in its presence, and melatonin had no further effect. Melatonin enhanced the release of proteins from cells, among them proteins recognized by specific TGFbeta1 antisera. The TGFbeta1-neutralizing antisera prevented the inhibitory action of melatonin on (3)H-thymidine incorporation into cells. CONCLUSIONS: These data indicate a role for TGFbeta1 in the melatonin-mediated attenuation of benign prostate epithelial cell growth.

Blotting, Western↗

Does preoperative nephrostomy increase the incidence of wound infection after nephrectomy?

OBJECTIVES: To determine whether patients with nephrostomy after simple nephrectomy more often had postoperative wound complication than did matched patients without nephrostomy. METHODS: The hospital records of patients who underwent retroperitoneal simple nephrectomy were evaluated, and the following data were retrieved: age, indication for nephrectomy and nephrostomy insertion, medical history, urine culture, antibiotic regimen, time elapsed from nephrostomy insertion to nephrectomy, surgical technique, type of complication, time elapsed from surgery to complication, treatment, and outcome of complications. RESULTS: Thirty-one patients (mean age 57.9 years, +/-SE 3.0) were evaluated. Seven (31.8%) of the 22 patients without nephrostomy (group 1 ) had wound infection compared with 7 (77.7%) of the 9 patients with nephrostomy (group 2) (P <0.05). All 9 group 2 patients had infected urine compared with 11 of the 22 in group 1 (P <0.05). Complications were apparent within a median time of 1 month (+/-SD 0.9) from surgery in group 2, whereas the median time to complication was 4.5 months (+/-SD 3.7, P <0.05) in group 1. Two patients in group 2 died of wound infection and sepsis. Both groups were similarly matched for age, indication for nephrostomy and nephrectomy, perioperative and operative techniques, and histologic findings of the removed kidneys. All patients received antibiotic agents at the time of surgery. CONCLUSIONS: Patients with nephrostomy inserted because of pyonephrosis or to relieve obstruction who underwent simple nephrectomy because of unrecoverable renal damage had earlier and more frequent wound infections than patients who underwent the identical procedure without nephrostomy. UROLOGY

Humans↗

Does the rate of extracorporeal shock wave delivery affect stone fragmentation?

OBJECTIVES: To evaluate the effect of the rate of shock wave delivery on stone fragmentation, because the optimal rate of shock wave administration has not yet been established. METHODS: Standard phantom, ball-shaped, ceramic stones were placed in a net-like basket with a hole size of 2.2 mm and immersed in a specially designed water bath coupled with the Econolith 2000 lithotripter. One hundred eighteen stones (mean diameter 9.5 mm) were used. Shock waves were delivered at rates of 30, 60, 90, 120, and 150 shocks/min and at intensities of 15, 20, and 22.5 kV (electrohydraulic). The number of shocks required for complete fragmentation, determined by all fragmented particles falling through the basket holes, was recorded. RESULTS: The most effective (fewer shocks needed for complete stone fragmentation) rate of shock wave delivery was 60 shocks/min. A statistically significant difference was demonstrated between the mean number of shocks required for complete stone fragmentation at the rate of 60 shocks/min and faster rates at all energy levels (P <0.01) but not between the rate of 60 shocks/min and the rate of 30 shocks/min at all energy levels. CONCLUSIONS: The rate of shock wave administration during extracorporeal shock wave lithotripsy seems to influence stone disintegration. We demonstrated that extracorporeal shock wave lithotripsy is most effective when waves are delivered at 60 shocks/min.

Lithotripsy↗

Rigiscan versus snap gauge band measurements: is the extra cost justifiable?

Both RigiScan and the Snap Gauge band devices are used to objectively measure penile rigidity. The Snap Gauge band is the more simple and inexpensive of the two techniques. We investigated the correlation between the results obtained by both devices in order to evaluate whether the Snap Gauge band could be employed as the sole method of rigidity evaluation while not affecting the quality of diagnosis. Forty eight patients who were presented to our erectile dysfunction clinic used the two devices simultaneously, each according to the accepted protocols. Breakage of two and three strings of the Snap Gauge (good rigidity) correlated well with good tip and average rigidity as evaluated by the RigiScan. Snap gauge results also correlated with duration of erection, number of erections, the number of adequate erections, and the longest duration of erection measured by the RigiScan. Therefore, good rigidity according to the Snap Gauge test correlated well with the results of functional erections (number, rigidity, duration) as obtained by the RigiScan. The Snap Gauge band can be used to adequately evaluate penile rigidity. RigiScan measurements, which are more complicated and more expensive, should be reserved for selected patients in whom the results of the Snap Gauge band are inconclusive or when more detailed information is required.

Adult↗

Elevated urinary fibronectin levels after transurethral resection of bladder tumour: a possible role in patients failing therapy with bacillus Calmette-Guérin.

OBJECTIVE: To investigate fibronectin levels in urine samples from patients with noninvasive transitional cell carcinoma (TCC) of the bladder immediately and for 4 weeks after transurethral resection of bladder tumour (TURBT), to determine whether soluble fibronectin within the bladder, which blocks the attachment of bacillus Calmette-Guérin (BCG), might lower the efficacy of BCG therapy over this period. PATIENTS AND METHODS: Urinary fibronectin was measured using an enzyme-linked immunosorbent assay in 25 patients with superficial bladder TCC who underwent TURBT for complete resection. Eight samples were collected for each patient, one before and seven during the 4 weeks after TURBT. RESULTS: High levels of urinary fibronectin were detected in 18 patients (72%) after TURBT. In 16 patients the fibronectin level returned to normal within 2 weeks of surgery. The other two patients showed elevated levels of fibronectin for > 4 weeks. CONCLUSIONS: These results show that urinary fibronectin concentration is significantly increased in most patients after TURBT and this should be considered in patients who receive BCG therapy. Treatment within the first 2 weeks after TURBT may be associated with a high failure rate, as urinary fibronectin levels were increased significantly in about three-quarters of these patients during that period. Indeed, the persistent elevation of fibronectin, occurring in two of the present patients, may be responsible for some of the failures of BCG therapy when it is administered 2-5 weeks after surgery.

BCG Vaccine↗

Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study.

OBJECTIVES: To determine, in a prospective randomized, double-blind placebo-controlled study, the effect of 6 weeks of high-dose (5 g/day) orally administered nitric oxide (NO) donor L-arginine on men with organic erectile dysfunction (ED). PATIENTS AND METHODS: The study included 50 men with confirmed organic ED who were randomized after a 2-week placebo run-in period to receive L-arginine or placebo. A detailed medical and sexual history, O'Leary's questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx), both stable metabolites of nitric oxide, were determined at the end of the placebo run-in period, and after 3 and 6 weeks. RESULTS: Nine of 29 (31%) patients taking L-arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with L-arginine and who had subjectively improved sexual performance had had an initially low urinary NOx, and this level had doubled at the end of the study. CONCLUSIONS: Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral L-arginine at the dosage used.

Administration, Oral↗

Melatonin receptors in PC3 human prostate tumor cells.

Melatonin, secreted nocturnally by the pineal gland, can bind to human benign prostate epithelial cells and attenuate their growth and viability. In the present study, melatonin binding and responses were explored in the human steroid-independent PC3 prostatic tumor cells. PC3 cells bound 125I-melatonin with low affinity (Kd ca. 0.9 nM) at high as well as low cell density. Melatonin enhanced cGMP and 3H-thymidine incorporation at low, but attenuated them at high cell density. In addition, melatonin inhibited cAMP at low, but augmented it at high cell density. These effects were associated with an increase in cell count at low- but not high-density cultures. Pertussis toxin treatment suppressed 125I-melatonin binding and ablated all the effects of melatonin on 3H-thymidine incorporation, cAMP, and cGMP at both cell densities. Cholera toxin treatment failed to block the effects of melatonin on 3H-thymidine incorporation, but prevented the modulation by melatonin of cAMP at low and cGMP at high cell density. The cGMP analog 8-Br-cGMP, inhibited melatonin's effects on 3H-thymidine incorporation at both cell densities. H89, a protein kinase A inhibitor, prevented melatonin's effects on 3H-thymidine incorporation at low but not high cell density. These results provide the first demonstration of direct interaction of melatonin with hormone-insensitive prostate tumor cells. The melatonin receptors in the PC3 cells are coupled to pertussis toxin-sensitive G proteins to induce cell density-dependent changes in cGMP, cAMP, and cell growth.

Binding Sites↗

Melatonin receptors in benign prostate epithelial cells: evidence for the involvement of cholera and pertussis toxins-sensitive G proteins in their signal transduction pathways.

BACKGROUND: Melatonin, the hormone secreted nocturnally by the pineal gland, binds to epithelial cells from the human benign prostate, and can reduce their growth and viability. The possible involvement of GTP binding proteins cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in melatonin responses in these cells were investigated. METHODS: The effects of melatonin on cAMP and cGMP were assessed in prostate cells untreated or pretreated with pertussis toxin (PTX) or cholera toxin (CTX). RESULTS: Melatonin augmented cAMP but reduced cGMP in the epithelial cells (maximal responses at 10 nM). The increase in cAMP was attenuated by PTX, but not by CTX, whereas the decrease in cGMP was attenuated by CTX, but not by PTX. CTX, but not PTX, abolished the melatonin-mediated suppression of 3H-thymidine incorporation. In addition, melatonin facilitated the CTX- and PTX-mediated ADP ribosylation of 44- and 41-kilodalton proteins, respectively. The cGMP analogue 8-bromo-cGMP, negated the melatonin-mediated decrease in 3H-thymidine incorporation, whereas H89, a protein kinase A inhibitor, did not inhibit melatonin's effect. CONCLUSIONS: Melatonin receptors in the human benign prostate epithelial cells enhance cAMP and inhibit cGMP through PTX- and CTX-sensitive G proteins, respectively. The decrease in DNA synthesis may be secondary to the melatonin-mediated decrease in cGMP.

Adenosine Diphosphate Ribose↗

Erectile dysfunction following Nd-YAG visual laser-assisted prostatectomy (VLAP).

We investigated if side fire Nd-YAG visual laser prostatectomy (VLAP) causes erectile dysfunction (ED) in patients who were sexually active prior to the procedure. The 36 study patients gave a detailed medical/sexual history: physical examination included bulbo-cavernous reflex (BCR) on rectal examination and routine blood tests. Lasing time, power of the applied laser beam (in watts), coagulation site and energy intensity were recorded. Patients with new onset ED during the one year study period underwent pudendal nerve conduction (PNC), color duplex Doppler ultrasonography, and NPT/RigiScan testing. In 6 out of 36 (16.7%) patients reporting significant post-operative ED, there was a tendency towards higher energy applied and longer lasing time but no correlation between prostate size or the site of energy application. Patients reported loss of night and/or morning erections (n = 5), retrograde ejaculations (n = 2), loss of ejaculate (n = 2), and decreased sensation of orgasm (n = 3). Three had abnormal PNC, duplex Doppler showed abnormal blood supply in four, and all six had abnormal NPT/RigiScan. We believe this is the first demonstration that VLAP may be associated with a high rate of ED and that the lasing time and intensity of applied laser energy may play a role in this outcome.

Aged↗

Evidence for a local action of melatonin on the rat prostate.

PURPOSE: Melatonin, secreted by the pineal gland at night, inhibits pubertal development in rats and possibly humans. We have recently found functional specific binding sites for 125I-labeled melatonin (125I-melatonin) in human benign prostate tissue, localized in the microsomal fraction of the glandular epithelium. The aim of the present study was to set up an animal (rodent) model for the growth inhibitory effects of melatonin on the prostate. MATERIALS AND METHODS: Putative melatonin in the rat ventral prostate were explored by means of autoradiography and receptor binding assays and the ability of melatonin to inhibit stimulated prostate growth was tested in vivo. RESULTS: In vitro autoradiography and equilibrium binding experiments demonstrated specific binding sites for 125I-labeled melatonin (125I-melatonin) associated with the microsomal fraction of the rat ventral prostate cells (apparent dissociation constant 0.9 nM). 125I-melatonin binding was inhibited by 2-iodomelatonin > 6-hydroxy-melatonin > melatonin = N-(2,4 dinitrophenyl)-5-methoxytryptamine whereas similar concentrations of serotonin, 5-methoxytryptamine, and tryptamine were less potent. The guanine nucleotide analogs, guanosine 5'-0-[3-thiotriphosphate] and guanosine 5'-0-[2-thio-diphosphate], inhibited specific 125I-melatonin binding whereas 5'-guanylyl imido-diphosphate was less potent. Daily injections of testosterone to castrated rats induced regrowth of the prostate and increased the weight of the seminal vesicles. Administration of melatonin to the rats through drinking water prevented the testosterone-mediated regrowth of the prostate but had no effect on the seminal vesicles' weight. CONCLUSIONS: The results demonstrate putative melatonin receptors in the rat prostate and suggest a direct suppression by melatonin of testosterone-dependent prostate growth.

Animals↗

Does severity of ischemic coronary disease correlate with erectile function?

An association between diminution in the quality of male sexual function and ischemic coronary disease has been suggested. Patients with ischemic heart disease who underwent coronary angiography participated in this study which aimed to document the impact of the extent of coronary disease upon sexual function in 40 patients (mean age 56.6 y). The 11-questions accepted questionnaire addressing sexual drive, erectile function, and ejaculation was used. Information regarding, age, medications, hypertension, diabetes, relevant risk factors, medical history, and the number of occluded coronary vessels was retrieved from the patients' records. A statistically significant correlation was demonstrated between erectile function and the number of coronary vessels involved. Patients with one-vessel disease had more (P < 0.04) and firmer erections (P < 0.001) with fewer difficulties in achieving an erection (P < 0.007) than men with two- or three-vessel disease. Age, diabetes, and hypertension also had a negative effect on the quality of the erection (P < 0.05) in all patients.

Adult↗

Inactivation of melatonin receptors by protein kinase C in human prostate epithelial cells.

The pineal hormone melatonin regulates seasonal reproduction and pubertal development in mammals. We recently found melatonin receptors in the human benign prostate tissue, primarily associated with the microsome-enriched fraction of the epithelial cells. In cultured benign prostate epithelial cells, melatonin, at physiological concentrations, suppressed [3H]thymidine incorporation and cGMP levels. The effects of melatonin were transient, suggesting inactivation of the receptors. In the present study, the possibility of inactivation of the prostate melatonin receptors by protein kinase C (PKC) was explored. Treatment of the microsome-enriched fraction with crude rat brain PKC in the presence of phorbol 12-myristate 13-acetate (TPA) or CaCl2 abolished the specific [125I]melatonin binding. This effect was prevented by the PKC inhibitor bisindolylmaleimide (GF-109203). [125I]Melatonin binding could be reinstated by iodoacetamide treatment. In benign prostate epithelial cells in culture, TPA pretreatment markedly reduced the apparent affinity of [125I]melatonin binding. In addition, TPA ablated the cells responses to melatonin, namely the suppression of [3H]thymidine incorporation and cGMP levels. Pretreatment with GF-109203 prevented the TPA effects on [125I]melatonin binding and responses. In addition, GF-109203 slowed down the inactivation of the melatonin-mediated inhibition of [3H]thymidine incorporation. Taken together, these data show that melatonin receptors are desensitized by PKC and imply that the transient response to melatonin may be the outcome of a direct or indirect melatonin-mediated activation of endogenous PKC.

Aged↗

Interplay between sex steroids and melatonin in regulation of human benign prostate epithelial cell growth.

Human benign prostatic epithelial cells contain functional melatonin receptors that can suppress cell growth and viability. The development of benign prostatic hyperplasia in men is assumed to result from androgen-estrogen imbalance. The impact of sex steroids on melatonin receptors in human benign prostate epithelial cells was investigated. The suppression by melatonin of [3H]thymidine incorporation and cGMP, and the enhancement of cAMP levels in the cells were used as markers of melatonin responses. Dihydrotestosterone (DHT) and 17 beta-estradiol (E2) separately increased [3H]thymidine incorporation into the cells, but suppressed it when combined. In cells grown with DHT, melatonin responses were extenuated. E2 greatly reduced the apparent affinity of [125I]melatonin binding in these cells without affecting binding site density. In parallel, the ability of melatonin to suppress [3H]thymidine incorporation into the cells was ablated within 1 h after the addition of E2. The melatonin-mediated increase in cAMP and decrease in cGMP concentrations were also ablated by E2. Preincubation of the cells with bis-indolylmaleimide (GF 102903X), a specific inhibitor of protein kinase C, prevented the E2-mediated inactivation of melatonin binding and the inhibitory action on [3H]thymidine incorporation. Prolonged (18-h) incubation of the cells with phorbol 12-myristate 13-acetate to down regulate protein kinase activity, partially restored [125I]melatonin binding and responsiveness in the E2-treated cells. These data indicate that 1) DHT and E2 enhance prostate epithelial cells growth, but reduce cell growth when combined; 2) DHT extenuates the inhibitory effects of melatonin on epithelial cell growth; and 3) E2 acts to inactivate melatonin receptors and consequently responses in human epithelial benign prostatic hyperplasia cells. This process is probably mediated by protein kinase C. Together, these results show an interplay between melatonin and sex steroids in the regulation of benign prostatic epithelial cell growth.

Aged↗

Is there an association between cigarette smoking and gland size in benign prostatic hyperplasia?

Several studies have implied a potential inhibitory effect of smoking on the development of clinical benign prostatic hypertrophy (BPH). None of these studies compared gland size and smoking habits. We prospectively test the hypothesis that the identified "negative risk factor" that cigarette smoke has on the development of clinical BPH is mediated through inhibition of gland growth. One hundred and ninety-five men underwent transrectal ultrasonography with prostate volume calculations. A self-administered questionnaire detailing smoking habits was completed by the subjects. Correlations were looked for between various smoking habit parameters and gland size. Prostate gland size did not differ between current smokers, ex-smokers, and never smokers. Prostate volume did not correlate with smoking years (duration of exposure), nor with intensity of exposure (cigarette packyears). Smoke-mediated changes in enzymatic and endocrine pathways that regulate prostatic growth have been well documented. However, whatever "protective" effects smoke may have on BPH, they are not mediated via direct inhibition on gland growth. Alternatively, cigarette smoke may be involved in changing the dynamic component of BPH. Further testing, with special emphasis on irritative and obstructive symptoms, may help elucidate this possibility.

Adult↗

Effect of elective prolonged urethral catheterization on serum prostate-specific antigen concentration.

OBJECTIVES: To determine the effect of an indwelling catheter on prostate-specific antigen (PSA) levels. PSA is an organ (prostate)-specific marker, and its level can be elevated in various pathologies as well as following urologic manipulations. An elevated marker may indicate the presence of prostate cancer. In the presence of an indwelling catheter, our inability to decide whether an elevated PSA value represents genuine pathology or is related to the catheter itself is often of great clinical importance. METHODS: A prospective study was conducted on 21 men with an indwelling catheter inserted electively for major nonurologic abdominal surgery to determine its influence on PSA concentration. Sera were collected before catheter insertion, 2 hours after, and then every day (average, 16 days). Catheters were left in place for an average of 5.5 days. RESULTS: Follow-up data compared to baseline and to the previous day's PSA concentrations revealed no significant change in any of the subjects. In 2 men with elevated preinsertion PSA levels (more than 10.0 ng/mL), the change over time did not differ in magnitude from changes in the other 19 men with normal pretreatment values. CONCLUSIONS: Inserting a urethral catheter and maintaining it for several days does not result in any clinically or statistically significant change in PSA levels. PSA values obtained in patients with an indwelling catheter are reliable and independent of its presence. An elevated level mandates prompt evaluation to exclude prostate cancer.

Aged↗

Effect of finasteride on free and total serum prostate-specific antigen in men with benign prostatic hyperplasia.

OBJECTIVE: To examine changes in the free-to-total (f/t) serum prostate-specific antigen (PSA) ratio among men treated with finasteride for benign prostatic hypertrophy. PATIENTS AND METHODS: Blood samples were taken from 20 men (mean age 71 years, range 61-87) before and after a minimum of 9 months of treatment with finasteride and the f/tPSA ratio determined using the Immulite assay system. RESULTS: Although mean total and free PSA levels decreased significantly, the mean f/tPSA ratio increased only slightly and not significantly; the ratios remained unchanged in men with an initially low or high (< > 10%) ratio. CONCLUSIONS: Concern has been expressed over the loss of the discriminatory power of serum PSA in a patient receiving treatment with finasteride. The f/tPSA ratio, currently used to help differentiate benign from malignant processes in the prostate, remains valid during treatment with finasteride; it does not affect the f/tPSA ratio.

Aged↗