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.     

Effects of montelukast on the healing of ischemic colon anastomoses

Background

The aim of this study was to examine whether treatment with montelukast, a selective leukotriene antagonist, would affect anastomotic healing in a reperfused colon rat model with remote ischemia/reperfusion injury.

Methods

Rats (n = 12 per group) were intraperitoneally administered normal saline or 10 mg/kg montelukast sodium 60 minutes before and for 5 days after surgery. Ischemia was induced for 45 minutes through superior mesenteric artery occlusion. A left colon anastomosis was made. Blood and perianastomotic tissue samples were obtained on postoperative day 5.

Results

Mean anastomotic bursting pressures of the control and montelukast groups were 159.17 ± 29.99 and 216.67 ± 26.40, respectively (P < .001). Compared with saline, montelukast treatment increased the mean tissue hydroxyproline level (2.46 ± .30 vs 3.61 ± .33 μmol/L) and decreased tissue caspase-3 activity (36.06 ± 5.72 vs 21.78 ± 3.87) and malondialdehyde levels (3.43 ± .34 vs 2.29 ± .34 nmol/g) (P < .001 for all). Other plasma markers of injury also showed differences.

Conclusions

Montelukast prevented ischemia/reperfusion-induced damage in a rat model of colonic anastomotic wound healing.     

Idiopathic granulomatous mastitis with erythema nodosum: Is it a variant of clinical presentation indicating treatment resistance? A retrospective cohort study

Idiopathic granulomatous mastitis (IGM) rarely occurs with erythema nodosum (EN) as a systemic finding. However, the impact of their coexistence on disease severity and response to steroids has not been investigated yet. Patients diagnosed with IGM between September 2014 and October 2018 were divided into two groups according to the presence or absence of EN during the first admission retrospectively. The IGM was more severe in patients with EN as it was presented more often as bilateral and diffuse involvement of the breast. Findings of mastitis did not resolve with steroids in 50% of this group. Repetitive excisions and mastectomy with reconstructions were required to control the disease. Coexistence of EN and IGM was found to be related to bilateral and aggressive involvement, which could be associated with insufficient response to steroids. Associated patients should be informed in terms of the aggressive course, and surgery can be highlighted as a first‐line treatment.     

Serum ghrelin, leptin and resistin levels in adolescent girls with polycystic ovary syndrome

Aim:  The aim of the present study was to investigate the levels of leptin, resistin and ghrelin in polycystic ovary syndrome (PCOS), and to assess their possible correlations with the hormonal and metabolic features of PCOS.
Methods:  Sixteen obese (ObPCOS) and 12 lean (LeanPCOS) subjects with PCOS and 19 obese control subjects were enrolled in the study.
Results:  Ghrelin, leptin and resistin concentrations were similar between groups when body mass index (BMI) was used as a covariate ( P  > 0.05). Mean androgen, SHBG, luteinizing hormone (LH) levels and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio tended to be similar between polycystic ovary syndrome (PCOS) groups. However, when compared with the control group, SHBG was lower and androgen, LH levels and LH/FSH ratio were higher in the PCOS groups. Free testosterone levels significantly correlated with resistin (r = −0.38), SHBG correlated significantly with body mass index (BMI) (r = −0.45) and resistin (r = −0.67), LH/FSH ratio was significantly correlated with ghrelin (r = −0.52) and estradiol (E2) levels (r = 0.51).
Conclusion:  ObPCOS and LeanPCOS groups having higher LH/FSH ratios and lower SHBG levels suggest that there could be factors other than adiposity responsible for the clinical features of PCOS patients. In the light of our results, those factors can be suggested as ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG.