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S Serels

Publications and source records attributed to S Serels.

8 recordsLinked to original sources

Intercellular communication in cultured human vascular smooth muscle cells.

Intercellular communication through gap junction channels plays a fundamental role in regulating vascular myocyte tone. We investigated gap junction channel expression and activity in myocytes from the physiologically distinct vasculature of the human internal mammary artery (IMA, conduit vessel) and saphenous vein (SV, capacitance vessel). Northern and Western blots documented the presence of connexin43 (Cx43) in frozen tissues and cultured cells from both vessels. Northern blots also confirmed the presence of Cx40 mRNA in cultured IMA and SV myocytes. Dual whole cell patch-clamp experiments revealed that macroscopic junctional conductance was voltage dependent and characteristic of that observed for Cx43. In the majority of records, in both vessels, single-channel activity was dominated by a main-state conductance of 120 pS, with subconducting events comprising less than 10% of the amplitude histograms. However, some records showed "atypical" unitary events that had a conductance similar to Cx40 (approximately 140-160 pS), but gating behavior like that of Cx43. As such, it is conceivable that the presence and coexpression of Cx40 and Cx43 in IMA and SV myocytes may result in heteromeric channel formation. Nonetheless, in terms of gating, Cx43-like behavior clearly dominates.

Aged↗

Priapism.

Priapism is a prolonged, painful, penile erection that fails to subside despite orgasm. An erection lasting longer than 4-6 h is considered to be priapic; nevertheless, pain does not usually ensue until 6-8 h have elapsed. Priapism is considered a failure of the detumescence mechanism, which may be due to excess release of contractile neurotransmitters, obstruction of draining venules, malfunction of the intrinsic detumescence mechanism, or prolonged relaxation of intracavernosal smooth muscle. There are essentially two main types of priapism: high flow (non-ischemic) and low flow (ischemic). Low flow priapism is the more common form, and it is associated with a decrease in venous outflow and vascular stasis that, in turn, cause tissue hypoxia and acidosis. This form of priapism is usually quite painful because of tissue ischemia. Penile blood aspirated from cavernous spaces appears dark in color. Immediate treatment is necessary or penile fibrosis will ensue. High flow priapism is usually due to trauma, although, on rare occasions it has been idiopathic or due to sickle cell disease. The hallmark of this type of priapism is an increase in arterial inflow in the setting of normal venous outflow. Aspirated penile blood is noted to be bright red and has a high pO(2). This form of priapism is not usually painful because it is non-ischemic. Treatment is dependent on the wishes of the patient but is not mandatory. International Journal of Impotence Research (2000) 12, Suppl 4, S133-S139.

Humans↗

Prospective study comparing hyoscyamine, doxazosin, and combination therapy for the treatment of urgency and frequency in women.

Anticholinergics are commonly used for the treatment of frequency, urgency, and urge incontinence in women. Alpha-blockers have been shown to have a modulating effect on bladder smooth muscle but are not commonly used clinically for this indication. To evaluate the clinical effectiveness of each treatment as well as the combination therapy, we performed an open prospective study comparing these agents. Between September 1994 and October 1995, 34 women aged 28-91 (mean age, 62) received either 0.375 mg of sustained-release hyoscyamine twice a day or 2 mg doxazosin QHS prior to being crossed over to the other drug and/or the combination. Symptoms were assessed using an expanded American Urological Association (AUA) symptoms score, which included questions regarding incontinence at completion of each therapeutic phase. Evaluation included 6-channel urodynamics. All three therapies were noted to be effective in reducing AUA symptom scores. By urodynamic evaluation, a greater percentage of patients with increased voiding pressures or decreased compliance responded to doxazosin than hyoscyamine. Side effects were noted to be less prevalent with doxazosin than with the other therapies. There appears to be a significant role for alpha-blockers in the treatment of voiding symptoms in women.

Adrenergic alpha-Antagonists↗

Molecular studies of human connexin 43 (Cx43) expression in isolated corporal tissue strips and cultured corporal smooth muscle cells.

Intercellular communication plays an important role in erectile function. The goal of this study, therefore, was two-fold. Firstly, to determine if cultured corporal smooth muscle cells provide a valid model system for evaluating the role of junctional communication to erectile physiology, and secondly, to explore the possibility that there may be age-related alterations in Cx43 mRNA expression. Human corpus cavernosum tissue was obtained from 31 patients with a mean age of 58 (range 27-89), while cell cultures were developed from 21 distinct patients with a mean age of 57 (range 26-59). Northern blots revealed that mRNA for Cx43 was expressed at detectable levels in all samples examined. It migrated as a transcript with an apparent size of 3.1 Kb. Western blots revealed the presence of multiple bands of Cx43 protein in both tissues and cells. However, Cx43 protein in tissue predominantly migrated as a 45 kDa band, while the Cx43 from cultured cells predominantly migrated as 41 kDa band. Cx43 mRNA expression was similarly heterogeneous in both frozen tissues and cultured cells. An approximately 3-5-fold increase in Cx43 mRNA levels was observed in cultured cells relative to frozen tissue, but the expression of Cx43 mRNA was not further altered upon passaging (p1-5). When Cx43 mRNA levels were normalized, and expressed as a ratio of the Cx43/beta-tubulin mRNA, there was a significant negative correlation between patient age and Cx43 levels on frozen tissues, but not on cultured cells. We conclude that: (1) There is similar heterogeneity/variability in Cx43 mRNA levels in frozen tissues and cultured cells derived from human corpus cavernosum. (2) That the expression of Cx43 mRNA in cultured cells is sufficiently stable, and similar to, expression levels in tissue as to provide a valid and physiologically relevant model system for further studying the role(s) of Cx43 in the regulation of penile erection. (3) There is a statistically significant, albeit modest, negative correlation between the Cx43/beta-tubulin ratio and patient age in frozen corporal tissue strips, but not on cultured corporal smooth muscle cells. Such observations provide further evidence for the plasticity of intercellular communication in the erectile process. Moreover, the similarities in the apparent regulation of Cx43 mRNA levels and that of the putative 'housekeeping' gene beta-tubulin, may suggest that Cx43 is constitutively synthesized in this tissue.

Adult↗

Endothelin-1 as a putative modulator of gene expression and cellular physiology in cultured human corporal smooth muscle cells.

PURPOSE: Increases in cytosolic calcium levels trigger smooth muscle contraction while nuclear calcium increases are thought to regulate gene expression. Endothelin-1 (ET-1) affects both. The goal of these studies was to further investigate the importance of ET-1 to corporal physiology by examining its actions on proliferation and immediate early gene (IEG) expression in cultured human corporal smooth muscle cells. MATERIALS & METHODS: Early passage (1-3) smooth muscle cells were grown in culture and exposed to either phenylephrine (PE) or ET-1 in the absence and presence of serum, the ET(A) or ET(B) selective antagonist BQ123 or IRL1038, or the L-type Ca2+ channel blocker, verapamil. Cell proliferation was assessed with a hemocytometer. The effects of ET-1 on c-myc and c-fos were evaluated using Northern blot analysis. Parametric or nonparametric statistics were used as appropriate. RESULTS: Addition of ET-1 (100 nM) to serum-starved cultured corporal smooth muscle cells was associated with a nearly 2-fold increase in cell number, as well as 2 to 6-fold increases in c-myc and c-fos levels. Cellular proliferation was inhibited by ET(A)- or ET(B)-receptor subtype blockade with BQ123 (1 microM) or IRL1038 (1 microM), respectively, or blockade of Ca2+ channels with verapamil (10 microM). PE (3 microM) had no detectable effect on smooth muscle proliferation. CONCLUSIONS: Cell proliferation was mediated by activation of the ET(A) and ET(B) receptor subtypes, dependent on transmembrane Ca2+ flux, and correlated with significant increases in c-myc and c-fos mRNA levels. These studies extend previous observations to indicate the potential pleotropic actions of this peptide in the regulation of human corporal smooth muscle physiology in vivo.

Adult↗

Biologic response modifiers in the management of superficial bladder cancer.

For the treatment of existing transitional-cell carcinoma or for prophylaxis of recurrent disease, intravesical therapy should be chosen according to stage. Papillary disease (stages Ta, Tl) may be treated effectively either with an alkylating agent or with bacillus Calmette-Guérin (BCG). BCG is the agent of choice for the treatment of Hat carcinoma in situ (Tis), with the recommended treatment course comprising 12 weekly and 12 monthly instillations. Intravesical interferon and many of the other biologic response modifiers mentioned herein may be effective for patients with Ta disease who have failed BCG therapy.

Administration, Intravesical↗