High dose zoledronic acid increases ischemia-reperfusion damage of the liver.

OBJECTIVE: Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, has been reported to exhibit a protective effect against cancers and prevent bone fractures. It also induces apoptosis by increasing proinflammatory cytokines and oxidative stress. Oxidative stress increases significantly during ischemia-reperfusion (IR) injury. The liver is highly sensitive to IR injury. In this study, we aim to investigate whether high-dose ZA treatment affects the liver during IR. MATERIALS AND METHODS: We used twenty-one Sprague-Dawley male rats in our study, and they were subdivided randomly into three groups, each containing seven rats. A single dose of 100 µg/kg ZA was administered via the intraperitoneal route in the ZA group. Forty-eight hours after the ZA administration, infrarenal abdominal aortic cross ligation was performed on the ZA and IR groups. After 2 hours of ischemia, 2 hours of reperfusion was applied. RESULTS: The malondialdehyde (MDA) level of the control group was significantly lower than the IR (p = 0.006) and ZA (p<0.001) groups. However, the superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) values of the control group were significantly higher than the values of the IR group (p<0.05, p<0.001, and p<0.05) and ZA group (p = 0.002, p<0.001, and p<0.001). Caspase-3 activity was significantly higher in the IR group as compared to the control group (p<0.001). The caspase-3 activity in the ZA group, on the other hand, was higher than both the control (p<0.001) and IR groups (p<0.001). CONCLUSIONS: High-dose ZA may exacerbate liver injury during IR by increasing reactive oxygen species production and apoptosis.

Helicobacter pylori can be related to carotid intima-media thickness, epicardial adipose tissue thickness and serum neutrophil gelatinase-associated lipocalin (NGAL) levels.

BACKGROUND: Helicobacter pylori (HP) affects the cardiovascular system. Our aim in this study was to evaluate, whether an infection with HP causes subclinical atherosclerosis. METHODS: We included 90 patients with dyspeptic symptoms in this study. The patients underwent an upper gastrointestinal endoscopy and biopsies were taken. The patients were grouped according to histopathologic examination, as HP infection negative (n = 21), HP infection positive (+) (n = 23), HP infection (++) (n = 22), HP infection (+++), (n = 24). RESULTS: The neutrophilic gelatinase-associated lipocalin (NGAL) and high-sensitive C-reactive protein (hs-CRP) levels and the carotid intima-media thickness (cIMT) and epicardial adipose tissue (EAT) thickness in the HP negative group were significantly lower than the NGAL (p < 0.001) and hs-CRP (p < 0.001) levels and the cIMT (p < 0.008) and EAT (p < 0.008) thickness in the HP (+++) group. There was a strong correlation between the serum NGAL and hs-CRP levels, cIMT and EAT thickness. CONCLUSION: HP-infection can lead to subclinical atherosclerosis via chronic inflammation. The higher the activity of HP infection, the higher the acceleration of atherosclerosis (Tab. 3, Fig. 2, Ref. 46). Text in PDF www.elis.sk.

Protective effects of thymoquinone and alpha-tocopherol on the sciatic nerve and femoral muscle due to lower limb ischemia-reperfusion injury.

OBJECTIVE: Thymoquinone (TQ) is an antioxidant and anti-apoptotic substance found in the Nigella sativa plant. Alpha-tocopherol (α-TP) is a potent antioxidant. We aimed to determine whether or not TQ and TP have a protective effect against lower limb ischemia-reperfusion (IR) injury of muscle and the sciatic nerve. MATERIALS AND METHODS: A single dose of TQ 25 mg/kg was given intraperitoneally to the TQ group, a single dose of α-TP 200 mg/kg was given intraperitoneally to the α-TP group. IR was performed for 45 minutes after the drugs' applications. RESULTS: While serum levels of malondialdehyde (MDA) and interleukin-6 (IL-6) of the IR group were significantly higher than those of the TQ plus α-TP, TQ and α-TP groups (p<0.001, p<0.001, p=0.008, respectively) and IL-6 (all p<0.001), the reduced glutathione (GSH) level of the IR group was lower than that of the other three groups. While neuronal nitric oxide synthase activity of nerve tissues of the IR group was significantly lower than that of the TQ plus α-TP group, the muscle tissue caspase-3 activity was higher than that of the TQ plus α-TP group. CONCLUSIONS: Administration of TQ plus α-TP may strongly protect muscle and nerve tissues against IR injury via their synergistic effects.

Relationship of osteoprotegerin to pulse wave velocity and carotid intima-media thickness in rheumatoid arthritis patients.

OBJECTIVE: Osteoprotegerin (OPG) is considered an important biomarker in cardiovascular (CV) disease. CV disease is the most common cause of mortality in patients with rheumatoid arthritis (RA), a consequence of accelerated atherosclerosis. The present study aimed to evaluate the relationship of serum OPG levels to arterial stiffness, carotid intima-media thickness (CIMT), and clinical and laboratory indices in RA patients. PATIENTS AND METHODS: Included in the study were 68 RA patients with no history or signs of CV disease and 48 healthy subjects Disease activity was assessed by the 28-joint disease activity score (DAS28) in RA patients. Serum OPG level was measured using enzyme-linked immunosorbent assay (ELISA). Carotid femoral pulse wave velocity (PWV) was measured as an index of arterial stiffness and CIMT was evaluated by carotid ultrasonography. RESULTS: The mean serum OPG level was significantly higher in RA patients than controls (p < 0.001). Mean PWV and CIMT were also significantly increased in RA patients compared to controls (both p < 0.001). In RA patients, serum OPG level was significantly correlated with PWV and CIMT, as well as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody; but not with DAS28, high-sensitivity C-reactive protein (hsCRP), or erythrocyte sedimentation rate. CONCLUSION: Serum OPG levels were increased and correlated with CIMT and PWV in RA patients. In addition to PWV and CIMT, OPG may be a useful biomarker for CV risk management in RA patients.

Topiramate has protective effect on renal injury.

BACKGROUND: Topiramate (TPM) decreases tumor necrosis factor-alpha (TNF-α) and oxidative stress. We investigated protective effects of TPM on cell damage in kidney tissue during ischemia-reperfusion (I/R) damage. METHODS: A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus TPM (I/R+TPM). Laparotomy without I/R injury was performed in control group. After laparotomy, cross ligation of infrarenal abdominal aorta was applied for two hours in I/R groups which was followed by two hours of reperfusion. TPM (100 mg/kg/day) was orally administrated to animals in the I/R+TPM group for seven consecutive days before I/R. RESULTS: The I/R group's TNF-α and interleukin-1 beta (IL-1ß) levels were significantly higher (1184.2 ± 129.1 pg/mg protein; 413.1 ± 28.8 pg/mg protein, respectively) than those of the control (907.8 ± 113.0 pg/mg protein, p = 0.002; 374.7 ± 23.7 pg/mg protein, p = 0.010, respectively) and I/R+TPM groups (999.5 ± 115.2 pg/mg protein, p < 0.001; 377.9 ± 30.9 pg/mg protein, p = 0.007, respectively). CONCLUSION: TPM may partially prevent renal damage in rats. The opening of new horizons of this kind of knowledge will help understand the complex challenge in the prevention of renal I/R damage (Tab. 1, Fig. 3, Ref. 42).

The association between serum YKL-40 levels, mean platelet volume, and c-reactive protein in patients with cellulitis.

BACKGROUND: Lower limb cellulitis is an infectious disease that has serious complications unless it is treated. OBJECTIVES: In this pilot study, we evaluated whether levels of YKL-40, an acute-phase reactant, and mean platelet volume (MPV), which occurs secondary to inflammation in cellulitis, increase compared to healthy subjects. We also aimed to investigate the association between YKL-40 and MPV in the prognosis of the patients. MATERIAL AND METHODS: A total of 55 patients with cellulitis (23 men and 32 women) and a similar age group of 46 healthy individuals (22 men and 24 women) were included in the study. Cellulitis was diagnosed according to guideline. Serum YKL-40 levels, MPV, C-reactive protein (CRP), and other biochemical values of both groups were compared. RESULTS: YKL-40 levels (52.2±34.5 ng/mL vs 34.6±18.0 ng/mL, P=0.004), MPV (7.7±1.0 fL vs 6.9±0.7 fL, P<0.001), and CRP (9.5±8.2 mg/dL vs 0.7±0.6 mg/dL, P<0.001) were significantly higher in the patients with cellulitis than the control. The mean recovery time (RT) of the patients was 22.6±6.9 days. We found that YKL-40 (odds ratio [OR] 0.1, confidence interval [Cl] 0.028-0.191, P=0.009) and MPV (OR 2.4, Cl 0.254-4.578, P=0.029) have an independent association with RT. CONCLUSION: YKL-40 and MPV values were correlated with higher CRP in the cellulitis group than in controls. According to these results, increased YKL-40 and MPV levels might be a prognostic factor for cellulitis in patients.

The protective effect of infliximab on cisplatin-induced intestinal tissue toxicity.

OBJECTIVE: Cisplatin (CP) is a popular chemotherapeutic agent. However, high doses of CP may lead to severe side effects to the gastrointestinal system. The aim of this study was to investigate the protective effects of infliximab on small intestine injury induced by high doses of CP. MATERIALS AND METHODS: The A total of 30 rats were equally divided into three groups, including sham (C), cisplatin (CP), and cisplatin + infliximab (CPI). The CP group was treated with 7 mg/kg intraperitoneal cisplatin, and a laparotomy was performed 5 days later. The CPI group received 7 mg/kg infliximab intraperitoneally, were administered 7 mg/kg cisplatin 4 days later, and a laparotomy was performed 5 days after receiving cisplatin. Histopathological and immunohistochemical analysis of small intestine tissue sections were performed, and superoxide dismutase, malondialdehyde, and TNF-α levels were measured. RESULTS: Histopathological evaluation revealed that the CP group had damage in the epithelium and connective tissue, but this damage was significantly improved in the CPI group (p < 0.05). In addition, these histopathological findings were confirmed by biochemical analyses. CONCLUSIONS: These results suggest that infliximab is protective against the adverse effects of CP.

Estimation by high-performance liquid chromatography of ketoprofen in plasma. Application to the study of its protein binding.

A method of estimation by high-performance liquid chromatography of ketoprofen in plasma is proposed. This method is rapid, simple, and very sensitive: it allows concentrations of 2 ng/ml to be determined. The internal standard is (benzoyl-4-phenyl)-2-butyric acid. The drug is extracted from a biological fluid in ether, which is then evaporated; the residue is taken up in chromatographic eluant (acetonitrile/phosphate buffer pH 7), analysed by reverse-phase chromatography and detected by spectrophotometry at 256 nm. In spite of the very strong protein binding of this drug, this method allowed the determination of its free concentration in plasma.