PubMed Health⌕ Search

Biomedical subjects

Stephen Zderic

Publications and source records attributed to Stephen Zderic.

7 recordsLinked to original sources
PubMed2006

Impact of state of arousal and stress neuropeptides on urodynamic function in freely moving rats.

Corticotropin-releasing factor (CRF) is a neurotransmitter in Barrington's nucleus neurons. These neurons can coregulate parasympathetic tone to the bladder (to modulate micturition) and brain noradrenergic activity (to affect arousal). To identify the role of CRF in the regulation of micturition, the effects of CRF agonists and antagonists on urodynamics in the unanesthetized rat were characterized. Rats were implanted with bladder and intrathecal or intraperitoneal catheters under isoflurane anesthesia. Cystometry was performed in the unanesthetized, unrestrained state at least 24 h later. In some cases, cortical electroencephalographic activity (EEG) was recorded simultaneously to assess arousal state. During cystometry, the state of arousal often shifted between waking and sleeping and urodynamic function changed depending on the state. Micturition threshold, bladder capacity, and micturition volume were all increased during sleep. The CRF1/CRF2 receptor agonists CRF and urocortin 2 increased bladder capacity and micturition volume in awake but not in sleeping rats. Conversely, the CRF1 receptor antagonists antalarmin and NBI-30775 increased urinary frequency and decreased bladder capacity in awake rats. The present results demonstrate a profound effect of the state of arousal on urodynamic function and suggest that simultaneous monitoring of EEG and cystometry may provide a useful model for studying nocturnal enuresis and other urinary disorders. In addition, the results provide evidence for an inhibitory influence of CRF in the spinal pathway on micturition. Targeting the CRF system in the spinal cord may provide a novel approach for treating urinary disorders.

Animals↗
PubMed2006

Lipid signaling changes in smooth muscle remodeling associated with partial urinary bladder outlet obstruction.

AIMS: Hypertrophy of the urinary bladder smooth muscle (detrusor) is associated with partial bladder outlet obstruction (PBOO). Hypertrophied detrusor smooth muscle (DSM) reveals altered contractile characteristics. In this study, we analyzed the lipid-dependent signaling system that includes phospholipase A2 in PBOO-induced DSM remodeling and hypertrophy to determine whether the release of arachidonic acid (AA) from phospholipid is altered in the detrusor. METHODS: Partial bladder outlet obstruction (PBOO) was produced by partial ligation of the urethra in New Zealand white rabbits. Two weeks after the surgery, the bladder function was studied by keeping the rabbits in metabolic cages for 24 hr. Bladders were removed from rabbits that had bladder dysfunction (increased urinary frequency and decreased void volume) and the DSM separated from mucosa and serosa. The isolated smooth muscle was incubated with [3H] AA to equilibrate the cytoplasmic AA. The level of AA release was compared with the level obtained with 2-week sham-operated rabbits. RESULTS: The rate of AA release was high in DSM from bladders with PBOO-induced hypertrophy. Carbachol stimulated AA release in control DSM but DSM from obstructed rabbits revealed no further increase from the elevated basal AA release. The half-maximal concentration of carbachol that was required to stimulate AA release from control samples of detrusor was 35 microM. CONCLUSIONS: The increased levels of AA release that are observed in this tissue after PBOO indicate the activation of phospholipase A2. The finding that carbachol could induce contraction, but not an increase in AA, indicates that the carbachol-induced contraction in the obstructed bladders is independent of lipid signaling pathways that involve AA. It is possible that the increased rate of arachidonic acid release from obstructed bladders correlates with the enhanced rates of prostaglandin production reported by other investigators from the same tissue.

Animals↗
PubMed2006

A second leiomyosarcoma in the urinary bladder of a child with a history of retinoblastoma 12 years following partial cystectomy.

This case describes a twin with bilateral retinoblastoma who developed leiomyosarcoma of the bladder at age 17 and again at 39. At 17-years of age she was diagnosed with a leiomyosarcoma of the bladder after presenting with recurrent urinary tract infections, hematuria, and dysuria. She was treated with partial cystectomy. After a 12-year disease-free interval, she was diagnosed with a second leiomyosarcoma of the bladder. This case supports the relationship between the genetic form of retinoblastoma and leiomyosarcoma and illustrates the necessity for extensive follow-up and well-defined treatment of secondary neoplasms.

Adult↗
PubMed2006

Insight on pathogenesis of varicoceles: relationship of varicocele and body mass index.

OBJECTIVES: Varicoceles, present in 15% to 20% of men, are the most common abnormal finding among men presenting with infertility, yet controversy exists regarding their etiology. Anecdotal experience suggests that varicoceles are more prevalent in lean men, supporting the "nutcracker" effect of the superior mesenteric artery compressing the left renal vein over the aorta. We examined this hypothesis in a large adult population. METHODS: A total of 2106 men were evaluated for infertility or erectile dysfunction from 1990 to 1996. The men were examined for the presence and severity of a varicocele. The association between age, height, body mass index, year of evaluation, and reason for consultation and the presence and severity of a varicocele was examined using logistic regression analysis. RESULTS: The mean age was 47 years (range 18 to 85), and the median body mass index was 26.4 kg/m2 (range 15.4 to 53.3). A varicocele was present in 398 men (18.9%). Stratified by grade, 59 (14.8%) were grade III, 155 (38.9%) were grade II, and 184 (46.2%) were grade I. The prevalence of varicoceles in the erectile dysfunction group (12.7%) was significantly less (P <0.001) than in the infertile group (32.2%). Multivariate logistic regression analysis revealed a statistically significant inverse relationship between body mass index and the presence of a varicocele. CONCLUSIONS: Varicoceles were less likely to be diagnosed among obese men. Although this suggests that the "nutcracker" phenomenon or other biophysical effects of increased adiposity may play a role in the pathogenesis, other factors could not be excluded as contributing to our findings.

Adolescent↗
PubMed2003

Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.

Partial urinary bladder outlet obstruction (PBOO) in men, secondary to benign prostatic hyperplasia, induces detrusor smooth muscle (DSM) hypertrophy. However, despite DSM hypertrophy, some bladders become severely dysfunctional (decompensated). Using a rabbit model of PBOO, we found that although DSM from sham-operated bladders expressed nearly 100% of both the smooth muscle myosin heavy chain isoform SM-B and essential light chain isoform LC17a, DSM from severely dysfunctional bladders expressed as much as 75% SM-A and 40% LC17b (both associated with decreased maximum velocity of shortening). DSM from dysfunctional bladder also exhibited tonic-type contractions, characterized by slow force generation and high force maintenance. Immunofluorescence microscopy showed that decreased SM-B expression in dysfunctional bladders was not due to generation of a new cell population lacking SM-B. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency correlated with overexpression of SM-A and LC17b. Myosin isoform expression and bladder function returned toward normal upon removal of the obstruction, indicating that the levels of expression of these isoforms are markers of the PBOO-induced dysfunctional bladders.

Animals↗
PubMed2002

Effect of partial outlet obstruction on rabbit urinary bladder smooth muscle function.

Bladder outlet obstruction secondary to benign prostate hyperplasia is associated with many cellular changes. This study was designed to determine whether these changes involve the contractile apparatus. Bladder smooth muscles from rabbits subjected to partial outlet obstruction for 2 wk were mounted for isometric force, isotonic shortening velocity, and myosin light chain (MLC) phosphorylation levels. Muscle strips from obstructed bladders exhibited spontaneous phasic activity; muscle strips from control bladders did not. Muscle strips from obstructed bladders exhibited increased sensitivity and higher levels of stress in response to the cumulative addition of KCl or carbachol compared with control. During noncumulative addition of KCl or carbachol, no differences in sensitivity were noted. Muscle strips from obstructed bladders had elevated basal MLC phosphorylation levels and stimulation produced small increases in MLC phosphorylation compared with control. V(max) during KCl stimulation of muscle strips from obstructed bladders was 10-fold lower than control. Our results suggest that bladder outlet obstruction produces a muscle cell that develops higher levels of force but with greatly reduced cross bridge cycling rates.

Animals↗