Endothelin 1 and transforming growth factor-ß1 correlate with liver function and portal pressure in cirrhotic patients.

OBJECTIVE: The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. MATERIALS AND METHODS: We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-ß1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4-6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. RESULTS: (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-ß1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-ß2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-ß1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. CONCLUSIONS: Peripheral endothelin-1 and transforming growth factor-ß1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

[Embolization of carotid arteria branch in stanching of nasal bleeding]. / Embolizacja galezi tetnicy szyjnej zewnetrznej w tamowaniu krwawien z nosa.

BACKGROUND: Epistaxis is a common clinical problem, especially in otolaryngology. This disorder affects equally both genders. Most cases manifest as spontaneous nasal bleeding. It can also appear as a result of trauma, high blood pressure, Osler-Rendu-Weber disease. When the bleeding is massive it can be potentially life-threatening. A great majority of epistaxis can be treated conservatively, if not it sometimes requires endovascular treatment. It is specially reserved for extensive, dangerous epistaxis. Angiography with selective embolization has become an accepted method of treating epistaxis that is not controlled with conservative methods. MATERIAL AND METHODS: Authors analyzed the efficacy of selective embolization treatment of epistaxis. 61 patients treated in the Department of Otolaryngology in Bialystok in years 1999-2011 were examined. There were 39 men and 22 women aged 24-48 years. Patients were referred for endovascular treatment when primary management was ineffective. Arteries suspected of bleeding were embolized superselectively. RESULTS: Immediate, complete control of bleeding was achieved in 100% patients. After few hours recurrent nasal bleeding occurred in 4 (7%) patients who underwent successful reembolization. There were no severe complications after procedure. Nine patients experienced few days lasting mild headache which disappeared after medicament treatment. Five patients suffered from unaided removing facial oedema. Out of 61 patients, 56 were available for 12-month follow-up evaluation. No neurological or otolaryngological complications were certified. There was also no relapse of epistaxis. CONCLUSIONS: Selective angiographic embolization is an effective method that should be considered in the treatment of refractory epistaxis. It is safe and not traumatic for patients.

Role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice.

Postmenopausal women frequently develop hypothyroidism. Estrogen depletion is accompanied by an increase of IL-6, accelerating bone turnover. The influence of hypothyroidism on bone metabolism in postmenopausal women is poorly understood. The aim of the study was an attempt to clarify the role of interleukin-6 on RANKL-RANK/osteoprotegerin system in hypothyroid ovariectomized mice. The study was performed on 56, 12-13 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6JIL6-/-Kopf (IL-6 knock-out; IL6KO). The mice were randomly divided into 8 groups with 7 mice in each one: 1/ WT controls, 2/ IL6KO controls, 3/ WT hypothyroid mice, 4/ IL6KO hypothyroid mice, 5/ WT ovariectomized, 6/ IL6KO ovariectomized, 7/ WT ovariectomized hypothyroid mice and 8/ IL6KO ovariectomized hypothyroid mice. Experimental model of menopause was produced by bilateral ovariectomy carried out in 8-9 weeks old mice. Experimental model of hypothyroidism was induced by propylthiouracyl administration in driking water. The serum levels of TRACP 5b, osteocalcin, OPG and RANKL were determined by ELISA. Serum RANKL concentrations were elevated significantly in all groups of ovariectomized mice as compared to respective controls, but in a minor degree in IL6KO hypothyroid mice as compared to wild-type animals. Moreover sRANKL values were significantly lower in IL6KO as compared to WT controls and IL6KO PTU injected mice. Osteoprotegerin serum levels were decreased in all IL-6 deficient mice and in a highest degree in sham-operated hypothyroid mice. To sum up, the results of the present study suggest that estrogens deficit is a strong stimulus for RANKL-RANK/OPG pathway that breaks an inhibitory influence of hypothyroidism even in IL-6 deficient mice.

Interleukin-6 is not essential for bone turnover in hypothyroid mice.

Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by an imbalance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) and osteocalcin in IL-6-deficient mice to assess the role of IL-6 in bone metabolism in hypothyroidism in mice. C57BL/6J (wild-type; WT) and C57BL/6J(IL6-/-Kopf) (IL-6 knock-out; IL6KO) mice randomly divided into 4 groups with 10 in each one: 1/ WT mice in hypothyroidism (WT-ht), 2/ WT controls, 3/ IL6KO mice with hypothyroidism (IL6KO-ht) and 4/ IL6KO controls. Experimental model of hypothyroidism was induced by intraperitoneal injection of propylthiouracyl. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentrations of TRACP 5b (median and interquartile ranges) were significantly decreased in both groups of mice with hypothyroidism: WT (3.2 (2.5-4.7) U/l) and IL6KO (2.6 (1.8-3.5) U/l) as compared to the respective controls. Similarly, serum osteocalcin levels were significantly reduced in both groups of mice in experimental hypothyroidism: WT (25.8 (23.0-28.2) ng/ml) and IL6KO (21.5(19.0-24.6) ng/ml) in comparison to the respective controls. There were no significant differences in bone turnover markers between IL6KO and WT mice both in hypothyroid and control animals. The results of the present study suggest that IL-6 does not play an important role in bone turnover in both euthyroid and hypothyroid mice.

Bone mineral density and bone metabolism are not related to leptin in hemodialyzed and peritoneally dialyzed uremic patients.

BACKGROUND: In chronic renal failure leptin levels are elevated and BMD decreased, however, so far data about correlations between leptin and BMD in dialyzed patients are scarce. It has been suggested that leptin is a predictor of BMD in postmenopausal women. We examined the relationships between leptinemia, BMD and bone metabolism in HD and CAPD patients. We also assessed whether leptin is significant and independent predictor of BMD in dialyzed patients. MATERIAL/METHODS: BMD was measured using dual energy X-ray absorptiometry (DEXA) at lumbar spine and femoral neck in 25 HD and 23 CAPD patients. Markers of bone turnover and leptin were studied using commercially available kits. RESULTS: In femoral neck BMD was significantly higher in CAPD patients, without significant differences in BMD in lumbar spine. There was a negative correlation between BMD at the femoral neck and time on hemodialysis (r= -0.45, p < 0.05). In CAPD patients BMD at the lumbar spine correlated negatively with vitamin D3 (r= -0.54, p < 0.05), osteocalcin (r= 0.54, p < 0 .05), and positively with BMI (r= 0.63, p < 0.01). BMD at the femoral neck correlated positively with BMI (r= 0.59, p < 0.01), and negatively with osteocalcin (r= -0.63, p < 0.05) and time on CAPD (r= -0.52, p < 0.05). Leptin correlate only with cholesterol (r= 0.25, p < 0.05), TSH (r= 0.35, p < 0.01), ss(2) microglobulin (r= 0.32, p < 0.001) and BMD at the femoral neck (r= -0.23, p < 0.05)in all dialyzed (HD and CAPD) patients. CONCLUSIONS: BMD depends on time of renal replacement therapy. Biochemical markers of bone metabolism poorly correlate with BMD and leptin in dialyzed patients. Leptin is not a predictor of BMD in dialyzed patients.