Does ultrastructural morphology of human detrusor smooth muscle cells characterize acute urinary retention?

PURPOSE: Acute urinary retention is relatively rare in otherwise healthy men. The condition may be attributable to a combination of obstruction and detrusor hypocontractility. We determined whether acute or chronic urinary retention is accompanied by characteristic ultrastructural features in bladder detrusor smooth muscle cells and whether any of these ultrastructural features may be useful for classifying these conditions. MATERIALS AND METHODS: Bladder biopsies of 15 men, including 13 in acute and 2 in chronic urinary retention, and 6 controls were examined by transmission electron microscopy. They were semiquantitatively and morphometrically analyzed for degenerative changes, cellular hypertrophy, variations in intercellular distances, abnormal cell junctions and configurations, and intracellular changes. RESULTS: No significant ultrastructural features were noted in the detrusor muscle of patients in acute urinary retention compared with controls. CONCLUSIONS: We cannot confirm the reports of others that characteristic ultrastructural features in smooth muscle cells accompany bladder outlet obstruction and detrusor hypocontractility.     

Do sperm parameters and infertility affect sexuality of couples?

We aimed to analyse the relationship between sperm parameters and International Index of Erectile Function (IIEF) score, the Female Sexual Function Index (FSFI) score, the testosterone (T) level in infertile men and between FSFI score and partners’ fertility. Patients were divided into three groups; (group 1: azoospermia [n = 57], group 2: sperm count <15 million [n = 41], group 3: sperm count >15 million [n = 81]). Patients and their partners filled the IIEF and FSFI forms. The normality of the tests was analysed with Kolmogorov–Smirnov and Shapiro–Wilk tests. Spearman's rho test, a nonparametric test, was used to correlate the data. A value of p < .05 was considered statistically significant. There was a positive correlation between the sperm count, other sperm parameters, morphology and motility and IIEF score, FSFI score and T (p = .037, .028 and .041 respectively). We found a positive correlation between IIEF score and FSFI score (p = .182). Infertile partners’ FSFI score was lower than fertile partners’ scores (p = .023). Male infertility causes severe sexual dysfunction in couples, and female sexual dysfunction increases in parallel to that of men. Male sexual function also tends to decrease with low sperm count. While the clinician evaluates infertile couples, psychological and sexual functions should also be evaluated and patients should not be deprived of appropriate treatment.     

Do NK-cell receptors and alloreactivity affect solid organ transplantation?

Although natural killer cells lyse targets without pre-sensitization, and in an MHC-unrestricted manner, they can also respond to healthy allogeneic cells of different MHC type. Such alloreactivity is a consequence of NK cells using clonally distributed, inhibitory MHC class I receptors to achieve tolerance to healthy autologous cells. Absence of an appropriate MHC class I ligand on an allogeneic cell erroneously informs the NK cell that the allogeneic cell has lost MHC class I expression and should be killed. Potential NK-cell allo-reactivities are common in non-HLA-identical hematopoietic cell transplants and can have both beneficial and detrimental effects. Less is known of NK-cell allo-reactivities in solid organ transplantation. In animal models NK cells are neither necessary nor sufficient for acute transplant rejection, but they can make a contribution by helping activate T cells. Genes encoding NK-cell receptors for polymorphic MHC class I molecules are also highly polymorphic, contributing to variability of the NK-cell repertoire and response in the human population. These receptors could represent intrinsic patient factors that influence the success of their transplanted solid organs.     

Do environmental and occupational exposure to pyrethroids and organophosphates affect human semen parameters? Results of a systematic review and meta-analysis

Our purpose was to review and analyse the impact of pyrethroids and organophosphates exposure on human semen parameters. A comprehensive literature search was performed through MEDLINE via PubMed, Scopus and Webscience. Only cohort studies examining semen parameters in workers or general populations exposed to pyrethroids or organophosphates were included. Ejaculate volume, sperm count, concentration, motility, viability, normal morphology and seminal pH alterations were pooled using the Cochran–Mantel–Haenszel Method with the random effect model and expressed as weighted mean difference, risk ratios, 95% confidence intervals and p-values. Seven cross-sectional studies regarding pyrethroids were included. Four of them were eligible for meta-analysis. The only parameter affected by pyrethroid exposure was normal sperm morphology (WMD-7,61%, 95%CI –11,92 to −3,30;p = 0,0,005). Nine studies were selected to evaluate the impact of organophosphates on semen parameters with six of them eligible for meta-analysis. A significant reduction was detected for the following: ejaculate volume (WMD −0,47ml, 95%CI −0,69 to −0,25; p < 0,0001), sperm count (WMD-40,03, 95%CI −66,81 to −13,25;p = 0,003), concentration (WMD-13,69 x10⁶/mL, 95%CI −23, 27 to-4,12;p = 0,005) and motility (WMD −5,70%, 95%CI −12,89 to 1,50;p = 0,12). Despite the increase in sperm abnormality, it has been shown that pyrethroids are unrelated to reduced sperm quality. However, the negative association of organophosphates with spermatogenesis is noteworthy.     

Beta-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of ��1A-adrenoceptors

Purpose

Alpha1A-adrenoceptors are important regulators of prostatic smooth muscle tone and an important target for therapy of lower urinary tract symptoms. The function of heptahelical transmembrane receptors such as adrenoceptors can be regulated by ??-arrestin-2, which may bind to receptors besides G proteins. Here, we investigated the expression and ??1A-adrenoceptor binding of ??-arrestin-2 in the human prostate.

Methods

Human prostatic tissues were obtained from patients undergoing radical prostatectomies. The expression of ??-arrestin-2 and ??1A-adrenoceptors was studied by RT?CPCR, Western blot analysis, and immunohistochemistry. The protein?Cprotein interaction between ??1A-adrenoceptors and ??-arrestin-2 was investigated by coimmunoprecipitation.

Results

RT?CPCR and Western blot analysis demonstrated the expression of ??-arrestin-2 mRNA and protein in the human prostate. Immunohistochemistry demonstrated ??-arrestin-2 expression in smooth muscle and stromal cells. Coimmunoprecipitation studies demonstrated that ??1A-adrenoceptors in the human prostate may interact with ??-arrestin-2. Thus, specific binding of ??-arrestin-2 to ??1A-adrenoceptors was significantly higher than background during ??1A-adrenoceptor detection in ??-arrestin-2 precipitates (P?P?Conclusion With ??-arrestin-2, we identified a new binding partner of the ??1A-adrenoceptor in human prostate smooth muscle. Binding of ??-arrestin-2 may be involved in posttranslational regulation of prostate ??1A-adrenoceptors.     

Do RANKL inhibitors (denosumab) affect inflammation and immunity?

Receptor activator of nuclear factor kappa B ligand (RANKL) and its natural antagonist, osteoprotegerin (OPG), are, respectively, an indispensable factor and a potent inhibitor for osteoclast differentiation, activity, and survival. The development of a human monoclonal antibody to RANKL, denosumab, constitutes a novel approach to prevent fragility fractures in osteoporosis, skeletal complications of malignancy, and potentially bone erosions in rheumatoid arthritis (RA). In addition to being expressed by osteoblasts, RANKL is abundantly produced by activated T cells, and synoviocytes in RA, whereas its receptor, RANK, is also expressed by monocytes/macrophages and dendritic cells. However, in preclinical and clinical studies of RA??including patients with some degree of immunosuppression??RANKL inhibitors did not significantly alter inflammatory processes. RANKL, RANK, and OPG deficiency in murine models highlights the important role of this pathway in the development and maturation of the immune system in rodents, including functions of T and/or B cells, whereas OPG overexpression in mice and rats seems innocuous with regard to immunity. In contrast, loss-of-function mutations in humans have more limited effects on immune cells. In clinical studies, the overall rate of infections, cancer, and death was similar with denosumab and placebo. Nevertheless, the risk of severe infections and cancer in some specific tissues remains to be carefully scrutinized.     

Do hydronephrosis and extracorporeal shock wave lithotripsy affect carbohydrate antigens?

Objectives

To investigate carbohydrate antigen (CA 19-9, CA 15-3, and CA 125) levels in the patients who had hydronephrosis with renal stones and in whom Extracorporeal shock wave lithotripsy (ESWL) was performed.

Materials and Methods

This prospective study included 20 people with no known disease for control group and 30 patients who had hydronephrosis with renal stones and in whom ESWL was performed between January 2005 and January 2006. None of patients had urinary infection and malignancy. The blood for carbohydrate antigens was taken pre-ESWL and 30 min after ESWL in both groups. CA 19-9, CA 15-3, and CA 125 in the serum were tested with the electro-immunoassay method on the Roche^® E-170 apparatus with the original Roche^® kit.

Results

The CA 19-9 and CA 125 values in the patients group were found to be statistically significant when compared with the control group but the CA 15-3 was not found to be significant. However, CA 19-9, CA 15-3, and CA 125 values of post-ESWL were not statistically significant when compared with pre-ESWL group (P > 0.05).

Conclusions

The average serum values of CA 125 and CA 19-9 in patients were found to be significantly high. However, serum values of CA 19-9, CA 15-3, and CA 125 were not affected by ESWL.

     

Do induced hypertension and hypotension affect stroke volume variation in man?

Study ObjectiveTo investigate changes in stroke volume variation (SVV) by both induced hypertension (pressor test) and hypotension (depressor test), and also by induced hypotensive anesthesia in patients with good cardiac function.DesignProspective, controlled clinical study.SettingUniversity hospital.Patients31 ASA physical status 1 and 2 patients, aged 39-62 years, who were scheduled for elective surgery.InterventionsWe conducted three studies: a pressor test study, a depressor test study, and an induced hypotensive anesthesia study. In the pressor test, patients received a bolus of phenylephrine 0.001 mg/kg to increase systolic arterial pressure (SAP) by 30% to 40% compared with baseline. In the depressor test, patients received a bolus of nitroglycerine 0.005 mg/kg to decrease SAP by 30% to 40% compared with baseline. In the induced hypotensive anesthesia test, patients received intravenous (IV) nitroglycerine continuously until mean arterial pressure (MAP) was reduced to 60-70 mmHg.MeasurementsWhen arterial pressure reached the target pressure for each study type, SVV and other parameters were recorded.Main ResultsInduced hypertension (pressor test) decreased SVV, while induced hypotension (depressor test) and induced hypotensive anesthesia increased SVV.ConclusionsSVV does not misinterpret preload dependency assessment of patients receiving medications to increase or to lower blood pressure.     

Does avulsion of the puborectalis muscle affect bladder function?

Introduction and hypothesis  The levator ani muscle is generally thought to play a role in urinary continence, with incontinence assumed to be due to abnormal muscle function or morphology. This study examined whether avulsion of the puborectalis muscle is associated with symptoms or signs of bladder dysfunction. Methods  In a retrospective observational study, we reviewed the records of 425 women who had attended a urogynecological unit for independent flowmetry, multichannel urodynamic testing, and 4D pelvic floor ultrasound. Results  Mean age was 55 years (range, 17–87 years). Of 420 women with complete datasets, 104 (25%) were diagnosed with a puborectalis muscle avulsion. These women were less likely to suffer from stress urinary incontinence (SUI; P < 0.001) and urodynamic stress incontinence (USI; P = 0.065) and more likely to present with symptoms of prolapse (P < 0.001) and show signs of voiding dysfunction (P = 0.005). The negative association between avulsion and SUI persisted in multivariate models. Conclusion  Puborectalis muscle trauma is not associated with an increased risk of SUI or USI in a urogynecological population, even when controlling for symptoms or signs of prolapse and previous surgery.     

Do gender and torus mandibularis affect mandibular cortical index? A cross-sectional study

Background

Vertical facial pattern may be related to the direction of pull of the masticatory muscles, yet its effect on occlusal force and elastic deformation of the mandible still is unclear. This study tested whether the variation in vertical facial pattern is related to the variation in maximum occlusal force (MOF) and medial mandibular flexure (MMF) in 51 fully-dentate adults.

Methods

Data from cephalometric analysis according to the method of Ricketts were used to divide the subjects into three groups: Dolichofacial (n = 6), Mesofacial (n = 10) and Brachyfacial (n = 35). Bilateral MOF was measured using a cross-arch force transducer placed in the first molar region. For MMF, impressions of the mandibular occlusal surface were made in rest (R) and in maximum opening (O) positions. The impressions were scanned, and reference points were selected on the occlusal surface of the contralateral first molars. MMF was calculated by subtracting the intermolar distance in O from the intermolar distance in R. Data were analysed by ANCOVA (fixed factors: facial pattern, sex; covariate: body mass index (BMI); alpha = 0.05).

Results

No significant difference of MOF or MMF was found among the three facial patterns (P = 0.62 and P = 0.72, respectively). BMI was not a significant covariate for MOF or MMF (P > 0.05). Sex was a significant factor only for MOF (P = 0.007); males had higher MOF values than females.

Conclusion

These results suggest that MOF and MMF did not vary as a function of vertical facial pattern in this Brazilian sample.     

Do Modic changes affect cervical sagittal alignment and motion in symptomatic patients?

Purpose

The cervical segmental instability often occurs simultaneously with Modic changes (MCs). However, it is unknown whether there is a relation between the two diseases. The aim of this study was to evaluate the relationship between MCs and cervical segmental instability, cervical curvature and range of motion (ROM) in the cervical spine.

Methods

A total of 464 patients with neck pain or cervical neurologic symptoms who underwent imaging examination were analyzed retrospectively. Based on MRI imaging cervical MCs were diagnosed, and patients were divided into with or without MCs groups. The cervical curvature and range of motion were measured. We compared the incidence of cervical instability, cervical curvature and ROM between the two group patients and their relationships with MCs were studied. Logistic regression was used to study the risk factors associated with MCs.

Results

MCs were observed in 94 of 464 patients and 122 of total 2320 cervical segments and were most frequent at C5–6 segment. The incidence of the cervical instability was significantly higher in patients with MCs than those without MCs at cervical level C3–7. In addition, cervical curvature and ROM in patients with MCs were less than those without MCs. Logistic regression analysis showed that the occurrence of cervical spine instability, less cervical curvature and ROM were risk factors for MCs.

Conclusions

Patients with MCs were prone to have cervical instability at the same cervical level and may have a higher possibility of less cervical curvature and ROM.

     

Blood loss in Duchenne muscular dystrophy: vascular smooth muscle dysfunction?

Patients with Duchenne muscular dystrophy (DMD) tend to bleed more during surgery than do patients with other conditions. A retrospective analysis of blood loss after spinal surgery for scoliosis was therefore undertaken in 102 patients undergoing surgery in the senior author's unit. These included 48 patients with DMD, 26 patients with spinal muscular atrophy, and a miscellaneous group of 28 other patients most of whom had idiopathic scoliosis. For each patient the age at surgery, estimated blood volume, duration of operation, Cobb angle, and number of vertebrae fused were recorded and compared. Expression of dystrophin in skeletal muscle and the underlying gene mutation were also determined. The estimated blood loss in patients with DMD was significantly higher than that in patients with spinal muscular atrophy undergoing the same or similar procedure (P < 0.005) and was also significantly greater than that of the third group, which consisted mostly of patients with idiopathic scoliosis (P < 0.0005). Blood loss in the patient group with DMD showed a significant relationship with duration of surgery (P < 0.05). As most patients expressed no dystrophin, this did not correlate with the estimated blood loss. There was also no correlation between the estimated blood loss and the type of gene mutation found causing DMD. The authors' previous observations confirm the increased blood loss in patients with DMD who undergo scoliosis surgery. Because children with DMD lack dystrophin in all muscle types, including smooth muscle, the excessive blood loss may be because of a poor vascular smooth muscle vaso-constrictive response due to a lack of dystrophin.     

Possible role of bioactive peptides in the regulation of human detrusor smooth muscle – functional effects in vitro and immunohistochemical presence

Results from basic research implicate a role for bioactive peptides in controlling the mammalian lower urinary tract. Although various peptides are assumed to be involved in the potentiaton or inhibition of cholinergic or purinergic activity in the urinary bladder, there is still much controversy regarding the mode of action and functional significance of such peptides in detrusor smooth muscle. Thus, we evaluated the functional effects of atrial natriuretic peptide (ANP), calcitonin gene related peptide (CGRP), endothelin 1 (ET-1), substance P (SP) and vasoactive intestinal polypeptide (VIP) on isolated strip preparations of human detrusor smooth muscle and determined the presence of those peptides in the human detrusor by means of immunohistochemistry. The effects of peptides on isometric tension of isolated detrusor strip preparations and on tissue levels of cyclic nucleotides cAMP and cGMP were compared to those of adenylyl cyclase activator forskolin (F), nitric oxide donor Na(+)-nitroprusside (SNP) and non-specific phosphodiesterase (PDE) inhibitor papaverine (P). The effects of the compounds on isometric tension of isolated human detrusor smooth muscle were examined using the organ bath technique. To determine time- and dose-dependent effects on cyclic nucleotide levels, bladder strips were exposed to increasing doses of F, SNP, P, ANP, CGRP and VIP, then rapidly frozen in liquid nitrogen and homogenised in the frozen state. cAMP and cGMP were extracted and assayed using specific radioimmunoassays. The presence of peptides was investigated by light microscopy using the Avidin-Biotin-Complex (ABC) method. F, P and VIP most effectively reversed the carbachol-induced tension of isolated human detrusor strips. Relaxing effects of ANP, CGRP and SNP were negligible. In contrast, ET-1 and SP elicited dose-dependent contractions of the tissue. The relaxing effects of F, P and VIP were accompanied by an increase in cAMP and cGMP levels, respectively. Light microscopy revealed positive immunostaining for CGRP, ET 1, VIP and SP in sections of the detrusor muscle coat. Our results suggest a possible importance of ET 1, SP and VIP in regulating detrusor smooth muscle contraction and relaxation. Even if a peptide is not synthesised, stored or released in a smooth muscle tissue and is, therefore, unable to reach its target cells under physiologic conditions, a functional effect on the tissue might be mediated by peptide-binding to specific cell surface receptors.