The role of statins in erectile dysfunction： a systematic review and meta-analysis

To evaluate the effect of statins for erectile dysfunction （ED）, a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials （RCTs） comparing treatment for ED with statins were identified. Placebo RCTs with the International Index of Erectile Function （IIEF） as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and five of them qualified for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a significant increase in IIEF-5 scores （mean difference （MD）： 3.27; 95% confidential interval （CI）：1.51 to 5.02; P〈 0.01） and an overall improvement of lipid profiles including total cholesterol （MD： -1.08; 95% Ch -1.68 to -0.48; P 〈 0.01）, low-density lipoprotein （LDL） cholesterol （MD： -1.43; 95% Ch -2.07 to -0.79; P 〈 0.01）, high-density lipoprotein （HDL） cholesterol （MD： 0.24; 95% Ch 0.13 to 0.35; P〈 0.01） and triglycerides （TGs） （MD. -0.55; 95% Ch -0.61 to -0.48; P 〈 0.01）. In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors （PDE51s）. However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.     

The role of tumor necrosis factor-α in Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP) is one of the most common types of vasculitis disorders in childhood and is characterized by a rash, arthritis, abdominal pain, and renal involvement. The factors that determine and mediate the severity of HSP and its renal involvement remain poorly understood, although it is likely that pro-inflammatory cytokines, including tumor necrosis factor- (TNF-), are involved in the pathogenesis. Serum and urine levels of TNF- were measured in children with HSP in the acute and convalescent phases by ELISA. Serum TNF- levels were significantly higher in proteinuric HSP in the acute phase (36.6±8.5 pg/ml) compared with those with HSP without renal involvement and those with hematuric HSP (25.4±4.5 and 27.1±3.9 pg/ml) (P<0.005). However, these significantly higher levels disappeared in the convalescent phase. Using matched serum samples from the same patients, serum TNF- levels of proteinuric HSP patients were significantly lower in the convalescent phase (29.9±4.6 pg/ml, P <0.05) than in the acute phase (39.1±8.2 pg/ml). Although urine TNF- levels were higher in proteinuric HSP in the acute phase and reduced in the convalescent phase, there were no significantly high or low levels. These results suggest that increased TNF- levels in the serum induce a series of functional and morphological changes in the glomerular cells in the acute phase and may be used as markers for monitoring the disease activity of HSP with severe renal involvement.     

MicroRNA-148b influences high glucose-induced endoplasmic reticulum stress in rat mesangial cell by targeting AMPKα1

Objective To observe the expression of microRNA-148b (miR-148b) induced by high glucose in rat mesangial cells, and to explore its effect on its target gene AMP-activated protein kinase α1 (AMPKα1) and extracellular matrix excretion. Methods Rat mesangial cells were divided into 3 groups: normal glucose (NG, 5.5 mmol/L glucose) group, hypertonic (MA, 5.5 mmol/L glucose+ 19.5 mmol/L mannitol) group and high-glucose (HG, 25.0 mmol/L glucose) group. MiR-148b expression was detected by real time PCR. Then miR-148b inhibitor was transfected to rat mesangial cells. Their protein expressions of AMPKα1, glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), fibronectin (FN) and collagen Ⅳ were detected by Western blotting. The expression of AMPKα1 mRNA was detected by real time PCR. The expression of collagen Ⅳ was also detected by immunofluorescence. Results Compared with NG group, HG group showed up-regulated miR-148b expression, down-regulated AMPKα1 mRNA and protein expressions, and up-regulated CHOP, GRP78, collagen Ⅳ and FN expressions (all P＜0.05). HG-induced mesangial cells with miR-148b inhibitor had up-regulated AMPKα1 mRNA and protein expressions, and down-regulated CHOP, GRP78, collagen Ⅳ, FN expressions as compared with HG-induced cells without miR-148b inhibitor (all P＜0.05). Conclusions HG can up-regulate miR-148b expression and down-regulate AMPKα1 expression in rat mesangial cells, then activate endoplasmic reticulum stress to induce extracellular matrix excretion. MiR-148b inhibitor up-regulates AMPKα1 expression, inhibits endoplasmic reticulum stress and reduces extracellular matrix excretion.     

A role for muscarinic receptors or rho-kinase in hypertension associated rat bladder dysfunction?

PURPOSE: Essential arterial hypertension is a frequent condition. Spontaneously hypertensive rats (SHRs) show bladder dysfunction similar to that seen in patients with overactive bladder. Since muscarinic receptors and rho-kinase have a key role in the regulation of bladder contractility, we determined whether alterations of either one might contribute to hypertension associated bladder dysfunction. MATERIALS AND METHODS: The bladders of SHRs and normotensive Wistar Kyoto rats (WKYs) were compared in in vitro radioligand binding and contractility studies. RESULTS: The mean total number of muscarinic receptors +/- SEM (181 +/- 14 vs 191 +/- 22 fmol/mg protein) and the relative roles of their subtypes were similar in SHRs and WKYs. Contractile responses to the muscarinic agonist carbachol (maximum effect 2.04 +/- 0.24 vs 2.05 +/- 0.14 mN/mm strip length and -log EC50 5.61 +/- 0.07 vs 5.64 +/- 0.04) and to KCl in a receptor independent manner were similar in the 2 strains. The M3 selective antagonist darifenacin inhibited carbachol responses much more potently than the M2 selective antagonist methoctramine but the potency of the 2 drugs was similar in each strain. The rho-kinase inhibitor Y27,632 attenuated carbachol induced contraction in a quantitatively similar manner in SHRs and WKYs. CONCLUSIONS: An altered function of muscarinic receptor subtypes or rho-kinase does not appear to contribute to bladder dysfunction in SHRs.     

The possible role of TNF-α and IL-2 in inducing tumor-associated metabolic alterations

This study was conducted to investigate the role of tumor necrosis factor- (TNF-) and interleukin-2 (IL-2) in inducing cancer cachexia, and the results were compared with those obtained from our previous study on Fisher 344 rats with methylcholanthrene-induced sarcoma. Three groups of male Fisher 344 rats received one of the following regimens: 4×10⁴ IU of human recombinant TNF- per rat per day subcutaneously (sc) for 5 consecutive days (n=5), 3.5×10⁵ U human recombinant IL-2 per rat per day sc for 14 consecutive days (n=5), or normal saline (n=5). The activities of both phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME) were increased slightly in the IL-2 group. Furthermore, LPL activity was significantly increased in the adipose tissue of the TNF group and in the cardiac muscle of the IL-2 group, but not in that of the TNF group. These results show that there is a significant difference between the metabolic alterations seen in the tumor-bearing state and those induced by either TNF- or IL-2 alone. Thus, it is unlikely that IL-2 or TNF- is the sole mediator of cancer cachexia in this tumor and rat model.     

Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells

Purpose

The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-α production in activated Kupffer cells.

Methods

Rats received LPS (500 μg/kg) under Urethane? sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or Intralipid? from 1 h before to 6 h after LPS administration. Some rats were treated with 10 mg/kg gadolinium chloride (GdCl₃) to induce Kupffer cell depletion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-α mRNA and protein expression, caspase-3 activation and apoptosis were evaluated in hepatocytes. Immunofluorescence staining revealed expression of the pan-macrophage marker CD68 as well as TNF-α in Kupffer cells.

Results

ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with Intralipid?-treated rats at 6 h after LPS administration, whereas propofol and GdCl₃ reduced the LPS-induced increases. LPS simultaneously augmented TNF-α expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF-α expression in Kupffer cells was inhibited by propofol and GdCl₃, resulting in a reduction of caspase-3 activity and apoptosis in LPS-treated rat hepatocytes.

Conclusions

Propofol (5 mg/kg/h) attenuated LPS-triggered liver dysfunction via inhibition of TNF-α production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo.

     

Impact of all-trans retinoic acid on COX-2 expression and Smad pathway in rat glomerular mesangial cells induced by TGF-β1

转化生长因子β1(TGF-β1)可能是致组织纤维化的核心因子,其经典信号通路为Smad通路.环氧化酶2(COX-2)是一种膜结合蛋白,在炎性反应中起重要作用.局部浸润的炎性细胞、肾小球的巨噬细胞、系膜细胞都是COX-2的来源[1].维甲酸能抑制肾脏纤维化,保护肾功能[2],其主要包括全反式维甲酸(atRA),92顺式维甲酸和132顺式维甲酸.本研究探讨atRA对肾小球系膜细胞TGF-β-Smad信号通路中COX-2表达的影响.     

Impact of all-trans retinoic acid on COX-2 expression and Smad pathway in rat glomerular mesangial cells induced by TGF-β1

转化生长因子β1(TGF-β1)可能是致组织纤维化的核心因子,其经典信号通路为Smad通路.环氧化酶2(COX-2)是一种膜结合蛋白,在炎性反应中起重要作用.局部浸润的炎性细胞、肾小球的巨噬细胞、系膜细胞都是COX-2的来源[1].维甲酸能抑制肾脏纤维化,保护肾功能[2],其主要包括全反式维甲酸(atRA),92顺式维甲酸和132顺式维甲酸.本研究探讨atRA对肾小球系膜细胞TGF-β-Smad信号通路中COX-2表达的影响.     

Is there a role of radial rigidity in the evaluation of erectile dysfunction?

RigiScan has been the most widely utilized device for measuring erectile rigidity. However, the use of the RigiScan in the evaluation of erectile dysfunction has questionable because the RigiScan device does not directly determine axial rigidity. The aim of this study is to clarify that radial rigidity measured by RigiScan reflects the intracorporeal pressure and erectile capability efficiently. From January 1998 to May 1999, a total of 23 patients with erectile dysfunction were involved in the study. They were evaluated by RigiScan and duplex ultrasonography after intracorporeal injection of prostaglandin E1. We investigated the relationship between radial rigidity and the resistance index. The results of radial rigidity were also compared with that of the degree of erection. For the entire group, significant correlations were found between radial rigidity and the resistance index (r=0.680, P<0.001 for tip rigidity; r=0.703, P<0.001 for base rigidity). In addition, for 12 patients whose tip rigidity exceeded 60% and for 10 whose base rigidity exceeded 60%, the correlations between radial rigidity and the resistance index remained (r=0.659, P=0.020 for tip rigidity; r=0.759, P=0.011 for base rigidity). Based on the response determined by patients, radial rigidity represented the degree of erection efficiently.Our findings suggest that RigiScan is a useful diagnostic tool. Radial rigidity represents the intracorporeal pressure efficiently and has an acceptable role in the evaluation of erectile dysfunction.     

Impact of PCI-neo-HGF on the expression of TGF-β1 and proliferation of glomerular mesangial cells in rats

肾小球系膜细胞(GMC)的过度增生是导致肾小球硬化及肾间质纤维化的重要机制之一[1].肝细胞生长因子(HGF)是一种多效性的细胞因子,其可通过加速细胞外基质降解,阻断小管上皮细胞转分化等实现对肾脏的保护[2-4].目前HGF对正常及增生的GMC是否有抑制作用尚不明确.本研究采用可在体内持续平稳表达的PCI-neo-HGF质粒进行研究[5],主要探讨HGF是否能抑制正常及脂多糖(LPS)刺激后的大鼠GMC的增生,以及这种作用是否与抑制转化生长因子β1(TGF-β1)的表达相关.     

Low-level laser therapy can reduce lipopolysaccharide-induced contractile force dysfunction and TNF-α levels in rat diaphragm muscle

Our objective was to investigate if low-level laser therapy (LLLT) could improve respiratory function and inhibit tumor necrosis factor (TNF-α) release into the diaphragm muscle of rats after an intravenous injection of lipopolysaccharide (LPS) (5 mg/kg). We randomly divided Wistar rats in a control group without LPS injection, and LPS groups receiving either (a) no therapy, (b) four sessions in 24 h with diode Ga–AsI–Al laser of 650 nm and a total dose of 5.2 J/cm², or (c) an intravenous injection (1.25 mg/kg) of the TNF-α inhibitor chlorpromazine (CPZ). LPS injection reduced maximal force by electrical stimulation of diaphragm muscle from 24.15 ± 0.87 N in controls, but the addition of LLLT partly inhibited this reduction (LPS only: 15.01 ± 1.1 N vs LPS + LLLT: 18.84 ± 0.73 N, P < 0.05). In addition, this dose of LLLT and CPZ significantly (P < 0.05 and P < 0.01, respectively) reduced TNF-α concentrations in diaphragm muscle when compared to the untreated control group.     

Impact of PCI-neo-HGF on the expression of TGF-β1 and proliferation of glomerular mesangial cells in rats

肾小球系膜细胞(GMC)的过度增生是导致肾小球硬化及肾间质纤维化的重要机制之一[1].肝细胞生长因子(HGF)是一种多效性的细胞因子,其可通过加速细胞外基质降解,阻断小管上皮细胞转分化等实现对肾脏的保护[2-4].目前HGF对正常及增生的GMC是否有抑制作用尚不明确.本研究采用可在体内持续平稳表达的PCI-neo-HGF质粒进行研究[5],主要探讨HGF是否能抑制正常及脂多糖(LPS)刺激后的大鼠GMC的增生,以及这种作用是否与抑制转化生长因子β1(TGF-β1)的表达相关.     

The role of the general practitioner in men's health

The general practitioner(GP)is pivotally placed as an access point to provide holistic healthcare for men.GPs are the gateway to men's health.It is the GP who has the power to impact on the present health and ameliorate the future health of men.With active health promotion and targeted advice and investigation,the healthcare shy man has the potential to look forward to a healthier,more fulfilled,and active life.     

The role of LFA-1 in the lysis of bladder cancer cells by bacillus Calmette-Guérin and interleukin 2-activated killer cells

Activated cytotoxic effector cells such as bacillus Calmette-Guérin (BCG)-activated killer (BAK) and lymphokine-activated killer (LAK) cells are thought to mediate the antitumor effects in the immunotherapy of superficial bladder cancer with BCG. We investigated the role of the leukocyte-function-antigen-1 and its two subunits CD11a and CD18 in the lysis of bladder tumor cells by both effector cell populations. We used flow cytometry to measure CD11a and CD18 expression on BAK and LAK cells. The involvement of both surface molecules in the lysis of bladder tumor cells was determined by phase contrast microscopy and a set of radioactive-release assays using specific inhibitory antibodies. BAK and LAK cells expressed more CD11a and CD18 on their surfaces than unstimulated peripheral blood mononuclear cells. Effector-target cell adhesion was a prerequisite for the cell-mediated cytotoxicity of BAK and LAK cells against bladder tumor targets. Cytotoxicity of both BAK and LAK cells was inhibited by a combination of anti-CD11a and -CD18 monoclonal antibodies. Our study gives further insight into the complex interactions of the adhesion molecules of activated immune cells and their respective tumor targets and might help to increase our knowledge of the molecular mechanisms of BCG-immunotherapy.