Distribution of alkaline phosphatase, osteopontin, RANK ligand and osteoprotegerin in calcified human carotid atheroma.

Ectopic vascular calcification is a significant component of atherosclerotic disease. Osteopontin (OPN), Osteoprotegerin (OPG), Receptor Activator of NFκB Ligand (RANKL), and alkaline phosphatase (ALP) are each thought to play central roles in the calcification or demineralization of atherosclerotic lesions. Abnormalities in the balance of these proteins may lead to perturbations in bone remodeling and arterial calcification. The purpose of this study was to measure the distribution of these proteins in human carotid lesions and to elucidate possible mechanism(s) whereby they control the deposition or depletion of arterial calcification. Thirty-three patients who had undergone carotid endarterectomy (CEA) within the previous 18 months and 11 control patients were enrolled. CEA specimens were analyzed by EBCT for calcification content in terms of Agatston (AGAT) and Volume scores. CEA specimens were then cut into 5 mm segments which were homogenized and extracted. Extracts were analyzed for tissue levels of calcium, phosphorus, ALP, OPN, RANKL, and OPG. Fasting blood samples were analyzed for the same components. In CEA tissue segments, the calcification levels (CHA AGAT) were inversely associated with the levels of OPG (r = -0.432/-0.579, p < 0.05) and positively associated with the levels of RANKL (r = 0.332/0.415, p < 0.05). In turn, the tissue levels of OPG were associated with homologous serum levels of OPG (r = 0.820/0.389, p < 0.001), and the tissue levels of RANKL were associated with the serum levels of homologous RANKL (r = 0.739/0.666, p < 0.0001). This study suggests that serum levels of OPG and RANKL may be useful biomarkers for estimating the degree of calcification in carotid atherosclerotic lesions.

Effects of levobupivacaine on wound healing.

BACKGROUND: Local anesthetic infiltration along the incision may be used to provide surgical anesthesia or postoperative analgesia. However, the effect of local anesthetics on wound healing remains controversial. In this investigation, we evaluated the effects of levobupivacaine on wound healing. METHODS: Sixty Wistar albino female rats weighing 230±20 g were included, with 10 rats in each group: group early c (early control): 3 mL isotonic saline; group early l1.25 (early levobupivacaine 1.25): 1.25 mg/kg per 3 mL levobupivacaine; group early l2.5 (early levobupivacaine 2.5): 2.5 mg/kg per 3 mL levobupivacaine; group late c (late control): 3 mL isotonic saline; group late l1.25 (late levobupivacaine 1.25): 1.25 mg/kg per 3 mL levobupivacaine; and group late l2.5 (late levobupivacaine 2.5): 2.5 mg/kg per 3 mL levobupivacaine. Rats in groups early c to early l2.5 were euthanized on the 8th day. Rats in groups late c to late l2.5 were euthanized on the 21st day. Wound tension strength, tissue hydroxyproline, and fibrotic index levels of the tissue samples from the early c and early l2.5 and late c and late l2.5 groups, respectively, on the 8th and 21st days were examined. RESULTS: Levobupivacaine decreased wound tension strength on the 8th day, especially a 2.5 mg/kg dose (P<0.001), and increased it on the 21st day (P<0.001). It also increased the inflammatory response (P<0.001) and collagen synthesis (8th day, P=0.109; 21st day, P=0.103) on both the 8th and 21st days. CONCLUSIONS: While levobupivacaine had a positive effect on wound healing during the early period, negative effects were observed thereafter. Additional studies at the molecular level are necessary to determine the cause of these apparently opposite effects.

Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury.

OBJECTIVE: Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury. MATERIALS AND METHODS: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups. RESULTS: APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p=0.032) and 28.5±8.2 (p<0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and p<0.001, respectively). CONCLUSIONS: PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.

Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.

BACKGROUND: In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity. MATERIALS AND METHODS: A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC. RESULTS: The tissue TNF-α, IL-1ß, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1ß levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue. CONCLUSIONS: Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.