Effectiveness of Palosuran in Bleomycin-Induced Experimental Scleroderma

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups—group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-β1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-β1 levels (p?<?0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-β1 levels (p?>?0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.     

Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p?<?0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p?=?0.001). Finally, in the 50–125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p?<?0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.     

Validation of multiple subject-specific finite element models of unicompartmental knee replacement

Accurate computer modelling of the fixation of unicompartmental knee replacements (UKRs) is a valuable design tool. However, models must be validated with in vitro mechanical tests to have confidence in the results. Ten fresh-frozen cadaveric knees with differing bone densities were CT-scanned to obtain geometry and bone density data, then implanted with cementless medial Oxford UKRs by an orthopaedic surgeon. Five strain gauge rosettes were attached to the tibia and femur of each knee and the bone constructs were mechanically tested. They were re-tested following implanting the cemented versions of the implants.Finite element models of four UKR tibiae and femora were developed. Sensitivity assessments and convergence studies were conducted to optimise modelling parameters. The cemented UKR pooled R² values for predicted versus measured bone strains were 0.85 and 0.92 for the tibia and femur respectively. The cementless UKR pooled R² values were slightly lower at 0.62 and 0.73 which may have been due to the irregularity of bone resections. The correlation of the results was attributed partly to the improved material property prediction method used in this project. This study is the first to validate multiple UKR tibiae and femora for bone strain across a range of specimen bone densities.     

Antioxidative effects of cysteamine,hyaluronan and fetuin on post‐thaw semen quality,DNA integrity and oxidative stress parameters in the Brown Swiss bull

The aim of this study was to compare the effectiveness of antioxidants including cysteamine (2.5, 7.5 mm ), hyaluronan (0.25, 1 mg ml^?1) and fetuin (5, 10 mg ml^?1) in the freezing of Brown Swiss bull semen. The best percentages of CASA motilities were achieved with 10 mg ml^?1 of fetuin and 2.5 mm of cysteamine. For sperm morphology, 10 mg ml^?1 of fetuin and 2.5 mm of cysteamine had better protective effects (P < 0.001). The results of hypo‐osmotic swelling test showed that the percentage values of membrane integrity in all the groups, excluding that supplemented with 5 mg ml^?1 of fetuin, were higher than those of the control group (P < 0.001). Results obtained for the DNA damage of sperm cells demonstrated that 0.25 mg ml^?1 of hyaluronan, and 2.5 and 7.5 mm of cysteamine led to lower rates of spermatozoa with damaged DNA, compared with the control group (P < 0.001). The maintenance of superoxide dismutase and glutathione peroxidase antioxidant activities following freeze‐thawing with 2.5 and 7.5 mm of cysteamine and 10 mg ml^?1 of fetuin was demonstrated to be at a higher level in comparison with the control group (P < 0.001). Malondialdehyde formation was found to be lower in the groups supplemented with 0.25 mg ml^?1 of hyaluronan and 7.5 mm of cysteamine after the freeze‐thawing process (P < 0.001).     

P wave dispersion is prolonged in patients with Wilson＇s disease

AIM： To investigate the P wave dispersion as a noninvasive marker of intra-atrial conduction disturbances in patients with Wilson＇s disease.
METHODS： We compared Wilson＇s disease patients （n = 18） with age matched healthy subjects （n = 15） as controls. The diagnosis was based on clinical symptoms, laboratory tests （ceruloplasmin, urinary and hepatic copper concentrations）. P wave dispersion, a measurement of the heterogeneity of atrial depolarization, was measured as the difference between the duration of the longest and the shortest P-waves in 12 lead electrocardiography.
RESULTS： All the patients were asymptomatic on cardiological examination and have sinusal rhythm in electrocardiography. Left ventricular and left atrial diameters, left ventricular ejection fraction and left ventricular mass index were similar in both groups. The Wilson＇s disease patients had a significantly higher P wave dispersion compared with the controls （44.7 ± 5.8 vs 25.7 ± 2.5, P 〈 0.01）.
CONCLUSION： There was an increase in P wave dispersion in cardiologically asymptomatic Wilson＇s disease patients which probably represents an early stage of cardiac involvement.     

<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine: a new insight into the pathogenesis of endometrial cancer

Objectives

The present study aims to specify the role of l-carnitine in the pathogenesis of endometrial cancer by comparing the serum total l-carnitine levels of endometrial cancer patients with those of healthy women.

Methods

Serum total l-carnitine concentrations were measured in patients with endometrioid-type endometrial cancer (n = 20) and healthy controls (n = 20) who were matched with respect to age and body mass index (BMI).

Results

Stage I endometrial cancer was diagnosed in 12 women (60.0 %) whereas three women (15.0 %) had stage II disease, three women (15.0 %) had stage III disease and two women (10.0 %) had stage IV disease. The healthy controls and endometrial cancer patients were statistically similar in aspect of age, gravidity, parity, BMI, waist-to-thigh ratio, waist-to-hip ratio, menopause, complete blood count parameters, and serum biochemistry. Serum total l-carnitine levels of women with endometrial cancer were significantly lower than those of healthy women (respectively, 5,519.4 ± 2,712.5 vs 7,940.8 ± 3,566.6 ng/dl, p = 0.021). Moreover, serum total l-carnitine levels decreased significantly and progressively with advancing stage (stage I vs II vs III vs IV; 6,294.0 ± 2,885.1 vs 5,800.0 ± 441.2 vs 4,016.0 ± 2,833.3 vs 2,560.0 ± 67.9 ng/dl; p = 0.021).

Conclusions

This is the first study to hypothesize that l-carnitine deficiency participates in the pathogenesis of endometrial cancer by means of a mechanism which is unrelated with obesity and increased amount of fat in human body.