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.

Atherogenic index of plasma may be strong predictor of subclinical atherosclerosis in patients with Behçet disease.

OBJECTIVES: Behcet's disease (BD) is a systemic vasculitis characterized by cardiovascular complications. Early diagnosis of these complications can reduce morbidity and mortality. Carotid artery intima-media thickness (cIMT) and the logarithmic value of triglyceride to high density lipoprotein ratio (atherogenic index of plasma, AIP) are good markers of atherosclerosis. The purpose of this study was to investigate whether AIP is a predictive marker of subclinical atherosclerosis in BD patients. PATIENTS AND METHODS: A total of 84 BD patients (60 male, 24 female) and 84 healthy control individuals (58 male, 26 female) were included in this study. cIMT measurements were made, and AIP values were calculated. RESULTS: cIMT (p < 0.001) and AIP (p < 0.001) values of the BD patients were higher than those of the control group. A strong independent relationship was found between the AIP value and cIMT (ß = 0.232, p = 0.018). In the subgroup analysis, the cIMT and AIP values of male BD patients were higher than those of female BD patients. CONCLUSION: Increased AIP and cIMT values can be a good marker for subclinical atherosclerosis in BD patients, especially in male BD patients.

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.

Serum YKL-40 levels as a novel marker of inflammation in patients with endometriosis.

PURPOSE: To establish serum YKL-40 concentrations in patients with endometriosis compared to age-matched healthy subjects. MATERIALS AND METHODS: This was a cross-sectional clinical study conducted in a tertiary care center. Demographics and serum YKL levels were determined and noted in a total of 63 cases (33 endometriosis patients, 30 healthy controls). Measurement of YKL-40 levels was made using a YKL-40 enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's protocol. RESULTS: The mean serum YKL-40 levels of the patient group was 106.0 +/- 15.9 (range 23.44 to 382.55) years, while the mean serum YKL-40 levels of the controls was 52.2 +/- 7.0 (range 22.35 to 160.0) years (p = 0.003). CONCLUSIONS: This is the first study evaluating serum YKL-40 levels in endometriosis. The present results indicate that YKL-40 levels were increased in patients with endometriosis compared to controls. The authors propose that circulating YKL-40 levels could be a novel biomarker for diagnosis and follow-up of endometriosis.

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.

Do hummingbirds see in ultraviolet?

We present a numerical model to fit the electroretinogram (ERG), a gross evoked eye visual potential, that originate in the retina through photons absorption by photoreceptors and then involve the contribution form others retinal neurons. We use the ERG measured in a hummingbird, to evaluate the most likely retinal mechanism - cones visual pigments and oil-droplets - that participate in their high dimensional tetra or pentachromatic color hyperspace. The model - a nonlinear fit - appears to be a very useful tool to predict the underlying contribution visual mechanism for a variety of retinal preparation.

Regional specificity of the long-term variation of tyrosine hydroxylase protein in rat catecholaminergic cell groups after chronic heat exposure.

The present study was carried out to investigate the effect of chronic heat exposure on tyrosine hydroxylase (TH) protein content in catecholaminergic rat brain-stem areas such as the anterior (LCA) and posterior (LCP) locus coeruleus, the substantia nigra (SN), the ventral tegmental area, and the dorsomedial (DMM) and the ventrolateral medulla and in the adrenal gland (AG). Male Sprague-Dawley rats were exposed to 34 degrees C during 3, 7, or 14 days. Controls were kept at 25 degrees C for the same period. In the LCA, TH content was decreased on day 7 (-34%) and 14 (-37%) of heat exposure. In the SN, TH protein content was decreased on day 7 (-25%) and 14 (-20%) after 34 degrees C. In the DMM cell group, 14 days at 34 degrees C produced a decrease (-20%) of TH content. In all of these structures, TH content variations were correlated with body temperature variations. In the AG, TH content increased progressively to peak (+31%) after 14 days of chronic heat exposure. This increase was also associated with body temperature modification. The selective and body temperature-related response to long-term TH protein content variations following chronic heat exposure observed in the LCA, SN, DMM, and AG could represent an adaptive physiological response of these catecholaminergic cells.

Effect of ingestion pattern on rehydration and exercise performance subsequent to passive dehydration.

Six male volunteers performed three tests, each comprising a passive heating session to obtain dehydration (loss of 2.6% body mass), followed by exercise on a treadmill until exhaustion (50% of maximal oxygen consumption) in a warm environment (dry bulb temperature 35 degrees C, relative humidity 20%-30%). In one test, the subjects exercised without rehydration (Dh). In the two other tests, 50% of the fluid lost in the dehydration session was replaced by drinking mineral water given either in one amount [913 (SEM 23) ml] before the exercise (Rh1) or divided into four equal portions [228 (SEM 5) ml] before the exercise and on three occasions at 15-min intervals during exercise (Rh4). Rehydration increased exercise duration in Rh1 compared to Dh [112 (SEM 7) min and 82 (SEM 3) min, respectively; P < 0.05]. The difference was not significant with Rh4 [103 (SEM 9) min]. A restoration of the time course of changes in plasma volume, plasma osmolality, heart rate and rectal temperature occurred immediately in Rh1 and as delayed in Rh4 until after 60 min of exercise. Our results demonstrated that the swift replacement of the fluid loss in the dehydrated subjects was beneficial to exercise performance by rapidly correcting the disturbances in body fluid balance.

Behavioral heterogeneity in Sprague-Dawley rats.

Because of consistent individual differences in animal behavior, it is often difficult to interpret experimental data. We therefore attempted to rank Sprague Dawley rats by a hierarchical ascendant clustering technique using data from avoidance conditioning and open-field testing (scores of exploratory activity before, during, and after an unpredictable noise stress, and calculated stress-related inhibition). This procedure allowed partition of the animal population into distinctive groups and subgroups, extremes being represented by low avoidance-low emotional and high avoidance-high emotional animals. These results are in discrepancy with others showing an opposite pattern of emotional responses in rat lines selectively bred for low or high avoidance. Considering the psychophysiological variability of the animal population in experimental designs may thus be more informative than classical statistical methods, particularly in the evaluation of drug effects or environmental adaptation.

Exertional heatstroke and muscle metabolism: an in vivo 31P-MRS study.

An impairment of muscle energy metabolism has been suggested as a predisposing factor for, as well as a consequence of exertional heatstroke (EHS). Thirteen young men were investigated 6 months after a well-documented EHS using 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). The relative concentrations of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), phosphomonoesters (PME), and the intracellular pH (pHi) were determined at rest, during a graded standardized exercise protocol (360 active plantar flexions) and during recovery. Also the leg tissue blood flow was determined by venous occlusion plethysmography during the MRS procedure. Sixteen age-matched healthy male volunteers served as control group. In resting muscle, there were no significant differences between the groups as regards pHi, Pi/PCr, and ATP/PCr+Pi+PME ratios. During steady state exercise conditions, effective power outputs were similar for both groups at each level of exercise: 20, 35, and 50% of maximal voluntary contraction (MVC) of the calf muscle. No significant differences were shown between the two groups in Pi/PCr, pHi, or changes of leg blood flow at each level of exercise. At 50% MVC, Pi/PCr was 0.48 +/- 0.08 vs 0.47 +/- 0.05 (P = 0.96), pHi was 6.94 +/- 0.03 vs 6.99 +/- 0.02, respectively (P = 0.13). Finally, the rate of PCr resynthesis during recovery was not significantly different between the two groups: t1/2 PCr = 0.58 +/- 0.07 vs 0.50 +/- 0.05 min, respectively (P = 0.35). Therefore, no evidence of an impairment of muscle energy metabolism was shown in the EHS group during a standardized submaximal exercise using 31P-MRS performed 6 months after an EHS.

Plasma atrial natriuretic peptide and vasopressin during thermal dehydration in supine posture.

After 30 minutes spent in an upright posture six healthy male subjects underwent two 130-minute experiments in a supine posture, the first in thermoneutral conditions (TC) and the second, 15 days later, in a hot environment (HE) in order to obtain a water loss of 2.5% body weight. In thermoneutral conditions, the supine posture induced plasma volume expansion, resulting in slightly lowered plasma vasopressin (AVP) levels and higher plasma atrial natriuretic peptide (ANP) levels, compared to the values obtained in the upright posture (P less than 0.05). During hot environment, the sweating-induced dehydration led to a significant reduction of plasma volume expansion and to an increase in rectal temperature and plasma osmolality (P less than 0.05). Plasma vasopressin levels were higher at the end of the heat exposure (P less than 0.05) but natriuretic peptide levels did not change, compared to the values observed in the upright posture. These data suggest that plasma volume reduction induced by thermal dehydration may limit the natriuretic peptide release, which occurs after changing from the upright to a supine position.

Plasma corticosterone response in continuous versus discontinuous chronic heat exposure in rat.

Effects of chronic exposure (25 days) to continuous (CHE) or discontinuous (DHE) hot environment (34 degrees C) on growth rate, food intake and cortico-adrenal function were studied in adult male rats. Growth rate and food intake were 40 and 31% less respectively in CHE and 7 and 9% less respectively in DHE than in control (CE) animals. The adrenal response to heat (40 degrees C) was reduced by 54 and 82% in CHE and DHE rats respectively but the plasma corticosterone (B) response to exogenous ACTH and ether stress was not altered by chronic heat. The plasma B rhythm was altered only in CHE rats which exhibited a 40% decrease in amplitude and a delayed nocturnal recession of plasma B values. These results indicate that 1) CHE induced major alterations of behavior specially during the nocturnal period of the L-D cycle, 2) that the altered circadian B rhythm of CHE rats could be linked to changes in feeding behavior and to reduced metabolic activity, 3) and that CHE induced a poorer adaptation than DHE.