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Biomedical subjects

A L Burnett

Publications and source records attributed to A L Burnett.

At least 19 recordsLinked to original sources
PubMed2001

A novel model of ischemia in renal tubular cells which closely parallels in vivo injury.

PURPOSE: Renal ischemia-reperfusion (IR) injury is a devastating clinical problem. While effective animal models have been developed to investigate this condition, they are limited by differential renal cell inflammatory mediator production and heterogeneous cell sensitivity to ischemia. We therefore developed an in vitro model of renal tubular cell ischemia that simulates the cellular injury observed in animal models of renal IR injury. MATERIALS AND METHODS: Using the established renal tubular cell line, LLC-PK1, simulated ischemia was induced by immersing the cellular monolayer in mineral oil. The effect of simulated ischemia on renal tubular cells was then determined by measuring the time course of TNF-alpha protein expression (ELISA), TNF-alpha mRNA induction (RT-PCR), and renal tubular cell apoptosis (TUNEL). RESULTS: Maximal TNF-alpha protein expression occurs following 60 min of simulated ischemia and 2 h of substrate replacement (reimmersion in media), and maximal TNF-alpha mRNA induction occurs following 60 min of simulated ischemia. Cellular apoptosis peaks following 60 min of simulated ischemia and 24 h of reperfusion. CONCLUSION: The time course of TNF-alpha production and apoptosis induction in this model closely parallels the time course for these markers in vivo. This study constitutes the initial demonstration that an in vitro oil immersion model of ischemia simulates the cellular injury (TNF-alpha production and apoptosis) observed in animal models of renal ischemia-reperfusion. This model may be used to study cellular mechanisms of IR in the absence of the systemic confounding variables.

Animals↗
PubMed2001

Novel pharmacological approaches in the treatment of erectile dysfunction.

The pharmacological treatment of erectile dysfunction has taken central importance among therapeutic approaches for this increasingly recognized, widespread disorder. In the past decade and a half, the specialty of erectile dysfunction management has witnessed an enormous growth in basic scientific interest which has been translated impressively to the clinical arena. Discoveries of regulatory mechanisms involved in penile erection have been garnered both at peripheral neurologic and end organ levels and at central brain and spinal cord levels. These discoveries along with ongoing investigations in the field provide a firm foundation for implementing exciting and effective erectile dysfunction pharmacotherapies both now and in the future. The purpose of this report is to review the current trends and new directions in the pharmacotherapy of erectile dysfunction.

Central Nervous System Agents↗
PubMed2001

Corporoplasty using pericardium allograft (tutoplast) with complex penile prosthesis surgery.

Penile prosthesis implantation can be challenging for such presentations as penile fibrosis and prosthesis erosion and conditions in which the corporal body is severely damaged or deficient. The technical complexity of some repairs and the infections associated with synthetic graft materials will sometimes pose limitations to using these materials. We offer a new role for Tutoplast processed pericardial allograft for complex corporoplasty during penile prosthesis surgery.

Aged↗
PubMed2001

General use of animal models for investigation of the physiology of erection.

In review, animal models have accounted significantly for the amazing strides made in the field of sexual dysfunction research. Fundamentally, they have offered a unique experimental approach to test many hypotheses regarding sexual function. Since their early use for sexual physiology research, there has been increasing sophistication using animals involving techniques for stimulating and monitoring sexual responses. One specific area that has been advanced is the use of conscious animal models to obtain a better sense of the natural contexts for sexual physiology and to avoid pharmacological interference associated with anesthetics. Another area of interest is the increasing use of simple but valid techniques to record and assess sexual responses. Efforts to develop and evaluate animal models that replicate disorders of sexual function have also been most advantageous. In the future, animal models will remain useful. The expanded applications of animal models include the study of predisposing disease states associated with sexual dysfunction and the study of all aspects of sexual dysfunction, in both male and female subjects. Continued judgment must be applied, understanding the advantages of one or another animal model, to explore questions and provide answers that are most scientifically relevant to the human condition. The promise of advancing therapies in this field indicates the additional prominent role for animals for the purposes of drug development.

Animals↗
PubMed2001

Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat.

PURPOSE: To explore the possible relevance of endothelial nitric oxide synthase (eNOS) in the pathophysiology of erectile dysfunction (ED) associated with diabetes mellitus, we compared the catalytic activity, protein expression, and cellular localization of eNOS with those of neuronal nitric oxide synthase (nNOS) in the penis of rats with alloxan-induced diabetes. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were given alloxan or vehicle only and monitored weekly by Dextrostix for confirmation of glucosuria. Tail-flick immersion and penile reflex testing were used to evaluate sensory neuropathy and ED, respectively. At 4 to 5 weeks (early) and 10 to 11 weeks (late), animals were sacrificed, and their penes were subjected to nNOS and eNOS catalytic activity assay, Western immunoblotting, and immunohistochemistry examination. Masson's trichrome staining of penile tissue and serum testosterone measurements were performed for light microscopy and sex steroidogenic analysis, respectively. RESULTS: Confirmed diabetic rats showed significant reductions in penile nNOS expression and eNOS activity and expression early, prior to observed ED, and nNOS and eNOS activities and expressions late, synchronous with ED. Decreased intensities of both nNOS staining, localized to the dorsal and cavernosal nerves distributing to the penis, and eNOS staining, localized to penile vascular and sinusoidal endothelium, were assessed in diabetic animals. Penile vascular and cavernosal tissue appeared intact in diabetic rats. Testosterone levels were equivalent in nondiabetic and diabetic rats. CONCLUSIONS: In the penis of the alloxan-induced diabetic rat, eNOS protein expression and synthetic activity were reduced compared with the normal rat penis, independent of testosterone influence and in the absence of significant erectile tissue degenerative changes. These eNOS effects apparently preceded nNOS effects. Full elucidation of the possible mechanisms affecting eNOS function in the diabetic rat penis requires further investigation.

Alloxan↗
PubMed2001

Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism.

Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signaling mechanisms of acute preconditioning, yet it remains unknown whether PKC mediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43 degrees C) for 1 h and heat shock protein (HSP) 72 induction was confirmed by Western blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) and B cell lymphoma 2 (Bcl(2)) expression (Western) was determined. Subsequently, the effect of PKC inhibition on HSP72 induction and heat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl(2) expression, and prevented simulated ischemia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. These data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.

Alkaloids↗
PubMed2000

Use of intraoperative video documentation to improve sexual function after radical retropubic prostatectomy.

OBJECTIVES: To determine whether arbitrary minor variances in surgical technique can have a major impact on the recovery of sexual function after radical retropubic prostatectomy. METHODS: The surgical procedures of 62 potent men were videotaped prospectively. Eighteen months after the study was initiated, the videotapes were reviewed and specific steps in the surgical procedure correlated with patient-reported potency rates. RESULTS: Four steps were identified that appeared to correlate with the recovery of sexual function: over-sewing back-bleeders from the proximal dorsal vein on the anterior surface of the prostate, division of the striated sphincter when placing urethral sutures, division of the posterior striated sphincter, and hemostasis at the end of the case. CONCLUSIONS: We believe that retrospective review of intraoperative videotapes has great promise. Because many surgeons use different techniques, it is likely that each individual may be able to identify other important arbitrary variations that may improve their patients' outcomes. Similarly, for surgeons with less than optimal outcomes, the review of early successful cases may enable them to identify ways that modification of their surgical technique can improve the outcome of future patients. To the best of our knowledge, the use of retrospective review of intraoperative videotapes has not been commonly used in any other surgical field.

Adult↗
PubMed2000

Patient-reported urinary continence and sexual function after anatomic radical prostatectomy.

OBJECTIVES: After radical prostatectomy, the rates for recovery of urinary continence and sexual function reported by experienced surgeons are much higher than the patient-reported outcomes from other centers. It is uncertain whether this represents differences in surgical technique or in the collection of data. This study was performed to determine patient-reported rates of continence and potency after radical prostatectomy performed by an experienced surgeon at a high-volume referral center for the treatment of localized prostate cancer. METHODS: Sixty-four men with localized prostate cancer who were potent preoperatively and who had sexual partners underwent anatomic radical prostatectomy between March 1997 and January 1998. A validated disease-targeted quality-of-life survey that assesses function and bother in two organ systems (urinary and sexual) was administered preoperatively and at 3, 6, 12, and 18 months postoperatively. RESULTS: Urinary continence, which was defined as wearing no pads, gradually improved during the first 12 months after surgery, and at 1 2 and 18 months, 93% of the patients were dry. Throughout the study, 93% to 98% of the patients characterized their urinary bother as none or small. Potency, defined as the ability to have unassisted intercourse with or without the use of sildenafil, improved gradually, and by 18 months, 86% of patients were potent and 84% considered sexual bother as none or small. Although one third of patients at 18 months were using sildenafil intermittently, only 2 patients were not able to have intercourse without its use. CONCLUSIONS: Patient-reported rates of continence and potency after radical prostatectomy performed by an experienced surgeon are high.

Adult↗
PubMed2000

Near infrared spectrophotometry for the diagnosis of vasculogenic erectile dysfunction.

A specialized near infrared spectrophotometry instrument for noninvasive, continuous monitoring of the hemodynamic events of erection in the human penis has been developed. Its potential application for the diagnostic evaluation of erectile dysfunction was investigated. Thirty-eight patients and 18 volunteer subjects underwent penile near infrared spectrophotometry using an optical sensor probe with wavelength selectivity for hemoglobin absorption spectra. Penile blood volume changes and their time courses were measured following intracavernous pharmacostimulation in patients and visual sexual stimulation in volunteers. Spectrophotometric results were compared with results obtained simultaneously using color duplex ultrasonography, strain gauge penile circumference monitoring, penile tonometry, and clinical assessments. Spectrophotometric recordings of penile erection showed measurable blood volume changes consistent with the hemodynamic events of this biological function. Blood volume per cent (BV%) increase correlated with clinical ratings of erection quality (P < 0.001), penile rigidity measurements (P < 0.005), and penile circumference increases (P < 0.0001), and it correlated with mean peak systolic velocity measurements when BV% increase was restricted to values less than 50% (P < 0.001). The time to reach half the maximum blood volume change (BV T1) correlated directly with the time to reach half the maximum penile circumference size increase (P < 0.001), whereas BV T4 correlated inversely with mean resistive index measurements only when BV T(1/2) was restricted to values greater than 120 s (P < 0.05). Spectrophotometric criteria consisting of BV % less than 35% and BV T(1/2) greater than 120 s affirmed the diagnosis of severe erectile impairment with a similar degree of accuracy as standard ultrasonographic criteria (P < 0.002). Penile near infrared spectrophotometry is a safe, inexpensive and simply used biomedical optics technique that provides quantitative measurements of the vascular physiology of penile erection and appears to offer clinical utility in the diagnosis of vasculogenic erectile dysfunction.

Adult↗
PubMed2000

Expression of penile neuronal nitric oxide synthase variants in the rat and mouse penile nerves.

Penile erection is mediated by nitric oxide (NO) synthesized by the neuronal nitric oxide synthase (nNOS). In the rat penis, the main nNOS mRNA variant, PnNOS, differs from cerebellar nNOS (CnNOS) by a 102 base pair insert encoding a 34-amino acid sequence. In the mouse, two nNOS mRNAs have been identified: nNOSalpha, encoding a 155-kDa protein, and an exon 2-deletion variant, nNOSbeta, encoding a 135-kDa protein that lacks a domain where a protein inhibitor of nNOS (PIN) binds. We wished to determine whether PnNOSalpha and beta are expressed in the rat penis and are located in the nerves and whether the beta form persists in the potent nNOS knock-out mouse (nNOS( big up tri, open big up tri, open)). A PnNOS antibody against the insert common to both PnNOSalpha and beta detected the expected 155-kDa protein in PnNOSalpha-transfected cells. This antibody, and the one common to PnNOS/CnNOS, showed (on Western blots) the 155- and 135-kDa nNOS variants in rat penile tissue during development and aging. PnNOSalpha mRNA and its subvariants were found as the main nNOS in the penile corpora, the cavernosal nerve, and the pelvic ganglia, with lower levels of PnNOSbeta mRNA. In tissue sections, PnNOS protein was immunodetected in the penile nerve endings in the rat and in the nNOS wild-type and nNOS( big up tri, open big up tri, open) mice. An antibody against the sequence encoded by exon 2 did not react (on Western blots) with the 135-kDa band, which confirms that this protein is the beta form. In conclusion, both PnNOSalpha and beta are expressed in the rat penis at all ages and are located in the nerves. The beta form may allow nitric oxide synthesis during erection to be partially insensitive to PIN. The residual expression of PnNOS, and possibly CnNOS, in the penis of the nNOS( big up tri, open big up tri, open) mouse occurs through transcription of the beta mRNA, and this may explain the retention of erectile function when the expression of nNOSalpha is disrupted.

Amino Acid Sequence↗
PubMed1999

Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase.

Nitric oxide (NO) acts as a neuronal messenger in both the central and peripheral nervous systems and has been implicated in reproductive physiology and behavior. Pharmacological inhibition of nitric oxide synthase (NOS) with the nonspecific NOS inhibitor, l-N(G)-nitro-Arg-methyl ester (l-NAME), induced deficits in both the number of ovarian rupture sites and the number of oocytes recovered in the oviducts of mice. Female neuronal NOS knockout (nNOS-/-) mice have normal numbers of rupture sites, but reduced numbers of oocytes recovered following systemic injections of gonadotropins, suggesting that NO produced by nNOS accounts, in part, for deficits in ovulatory efficiency observed after l-NAME administration. Additionally, endothelial NOS knockout (eNOS-/-) mice have reduced numbers of ovulated oocytes after superovulation. Because endothelial NOS has been identified in ovarian follicles, and because of the noted reduced breeding efficiency of eNOS-/- mice, the present study sought to determine the role of NO from eNOS in mediating the number of rupture sites present after ovulation. Estrous cycle length and variability were consistently reduced in eNOS-/- females. The number of rupture sites was normal in eNOS-/- mice under natural conditions and after administration of exogenous GnRH. After exogenous gonadotropin administration, eNOS-/- females displayed a significant reduction in the number of ovarian rupture sites. Female eNOS-/- mice also produced fewer pups/litter compared to WT mice. These data suggest that NO from endothelial sources might play a role in mediating rodent ovulation and may be involved in regulation of the timing of the estrous cycle.

Animals↗
PubMed1999

Ejaculatory abnormalities in mice lacking the gene for endothelial nitric oxide synthase (eNOS-/-).

Nitric oxide (NO) has been established as a neurotransmitter in both the central and peripheral nervous systems. Three isoforms of its synthetic enzyme, NO synthase (NOS), have been identified: 1) in the endothelial lining of blood vessels (eNOS), 2) an inducible form found in macrophages (iNOS), and 3) in neurons (nNOS). Previous studies using pharmacological agents that block all three isoforms of NOS have revealed that NO mediates several aspects of reproductive physiology and behavior, including anomalies in male sexual behavior and erectile function. To determine the specific contribution of the endothelial isoform of NOS in male reproductive behavior, we studied mice missing the gene for only eNOS (eNOS-/-). Wild-type (WT) and eNOS-/- animals were placed with an estrous WT female and observed for 45 min. Both WT and eNOS-/- mice displayed equivalent motivation to mount the stimulus female. However, eNOS-/- mice exhibited striking anomalies in ejaculatory function. A higher percentage of eNOS-/- than WT mice ejaculated during the testing period (p < 0.001). This increased propensity to ejaculate was apparently due to reduced stimulation required to elicit ejaculation; eNOS-/- mice required significantly fewer mounts (p < 0.003) and intromissions (p < 0.001) to ejaculate compared to WT mice. Taken together, these results suggest that NO synthesized by eNOS may be involved in ejaculatory physiology, but not sexual motivation.

Animals↗
PubMed1999

EDITS: development of questionnaires for evaluating satisfaction with treatments for erectile dysfunction.

OBJECTIVES: To develop Patient and Partner versions of a psychometrically sound questionnaire, the EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction), to assess satisfaction with medical treatments for erectile dysfunction. METHODS: Treatment satisfaction differs from treatment efficacy as it focuses on a person's subjective evaluation of treatment received. Twenty-nine items representing the domain of treatment satisfaction for men and 20 representing partner satisfaction were generated. Two independent samples of 28 and 29 couples completed all items at two points in time. Spearman rank-order correlations were derived to assess test-retest reliability and couple coefficients of validity. Internal consistency coefficients were calculated for both Patient and Partner versions and a content validity panel was used to analyze content validity. RESULTS: Only items that met all the following criteria were selected to comprise the final questionnaires: (a) range of response four or more out of five; (b) test-retest reliability greater than 0.70; (c) ratings by at least 70% of the content validity panel as belonging in and being important for the domain; and (d) significant correlation between the subjects' and partners' responses. Eleven patient items met criteria and formed the Patient EDITS; five partner items met criteria and formed the Partner EDITS. Scores on the two inventories were normally distributed with internal consistencies of 0.90 and 0.76, respectively. Test-retest reliability for the Patient EDITS was 0.98; for the Partner EDITS, it was 0.83. CONCLUSIONS: Reliability and validity were well established, enabling the EDITSs to be used to assess satisfaction with treatment modalities for erectile dysfunction and to explore the impact of patient and partner satisfaction on treatment continuation.

Erectile Dysfunction↗