Effects of melatonin on lipid peroxidation and antioxidative enzyme activities in the liver,kidneys and brain of rats administered with benzo(a)pyrene

Benzo(a)pyrene [B(a)P] is a widespread pollutant with a mutagenic, carcinogenic and strong prooxidative properties. The present study evaluated the melatonin effects on lipid peroxidation products levels and on activity of antioxidative enzymes in the course of B(a)P intoxication. Control rats were treated with 0.9% NaCl; another group was given 10 mg melatonin/kg bw; a third group was injected twice a week with B(a)P at the dose of 10 mg/kg bw; the fourth group received both B(a)P and melatonin at the dose as mentioned above. The experiment continued for 3 months. In homogenates of brain, liver and kidneys lipid peroxidation was appraised by evaluation of malonyldialdehyde and 4-hydroxyalkenal (MDA+4HDA) levels. Activities of glutathione peroxidase (GPx), superoxide dysmutase (SOD) and catalase (CAT) and concentration of reduced glutathione (GSH) were also estimated. In animals receiving both B(a)P and melatonin, lower levels of MDA+4HDA were observed in all organs as compared to the group treated with B(a)P only. Following administration of B(a)P, GSH level decreased in brain and kidney. Melatonin in combination with B(a)P induced rises in the GSH level in liver and brain, as compared to the receiving B(a)P alone. The activity of SOD increased in the rats treated with melatonin alone but the highest activity was observed in rats treated with B(a)P plus melatonin. CAT activity in the melatonin-treated group increased in brain and liver. Similar to SOD, activity of the enzyme significantly increased in the group treated in combination with B(a)P and melatonin, as compared to the remaining groups in all tested tissues. The results suggest that melatonin protects cells from the damaging action of B(a)P. According to our knowledge, there are no studies describing the effects of melatonin on lipid peroxidation markers and antioxidative enzymes during intoxication of B(a)P in the brain, liver and kidneys. The results of present study give a perspective for further studies of its free radical scavenger properties in prevention of oxidative stress dependent diseases, among others cancers caused by carcinogens such as B(a)P.     

Staphylococcus epidermidis and biofilm‐associated neutrophils in chronic rhinosinusitis. A pilot study

A key role of bacterial biofilm in the pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP) is commonly accepted. However, the impact of some bacterial species isolated from inflamed sinus mucosa on biofilm formation is unclear. In particular, the role of Staphylococcus epidermidis as aetiological agents of CRS is controversial. Moreover, the effect of biofilm formation on neutrophil infiltration and activity in CRSwNP calls for explanation. In this study, biofilms were found in three of 10 patients (mean age = 46 ± 14) with CRS undergoing endoscopic sinus surgery by means of scanning electron microscopy. Unexpectedly, S. epidermidis was the primary isolated bacteria and was also found to be present in all biofilm‐positive mucosa specimens, indicating its pivotal role in the pathogenesis of severe chronic infections associated with biofilm formation. We have also measured the activity of myeloperoxidase (MPO), the most abundant neutrophil enzyme, to demonstrate the presence of neutrophils in the samples tested. Our present results show that the level of MPO in CRS associated with biofilm is lower than that without biofilm. It may suggest either a low number of neutrophils or the presence of a type of neutrophils with compromised antimicrobial activity, described as biofilm‐associated neutrophils (BAN). Finally, we conclude that further studies with a large number of CRS cases should be performed to establish the association between S. epidermidis and other frequently isolated bacterial species from paranasal sinuses, with the severity of CRS, biofilm formation and the infiltration of BAN.     

Endothelial Markers: Thrombomodulin and Von Willebrand Factor and Risk of Kidney Thrombosis After Transplantation

ObjectiveEndothelial disturbance is well known as one of the causes of thrombosis. This study measured von Willebrand factor (vWF) and soluble thrombomodulin (sTM) in renal vein blood to evaluate for the risk of thrombosis after kidney transplantation.MethodsA cross-sectional study that included 61 consecutive recipients of kidney transplant. The sTM and activity of vWF were evaluated in blood of the renal vein at the time of reperfusion.ResultsThe renal vein blood had higher values of vWF activity and sTM concentration than the peripheral blood. In the first minutes of reperfusion, the concentration of thrombomodulin was the highest but activity of vWF was the lowest. As the reperfusion continued, thrombomodulin gradually decreased, but vWF increased. The strong correlations of TMs and vWF with warm ischemia were observed (r = 0.5577 and r = 0.3429, respectively). Thrombosis was found in about 10% of all recipients. However, other complications, such as delayed graft function or ureter necrosis, were associated with high values of vWF and sTM. They were correlated with increased sTM concentration and activity of vWF (P < .006 and P < .05, respectively). This was confirmed by analysis of the receiver operator characteristic curve. The area under the curve values for TMs and vWF were 0.762 and 0.602, respectively (P < .0001 and P < .015, respectively). The cutoff points for sTM and vWF were 14.89 ng/mL and 129.89%, respectively. Positive prediction value sTM and vWF were 76% and 66% and negative prediction value 69% and 59%, respectively.ConclusionsThe endothelium of a transplanted kidney could be involved in the pathogenesis of renal thrombosis. Endothelial protection during harvesting can greatly contribute to the improvement of transplantation outcomes. The renal pool of sTM and vWF could be a useful marker of the risk of renal thrombosis.     

The effect of experimental long-term exposure to low-dose zearalenone on uterine histology in sexually immature gilts

The objective of this study was to determine whether long-term (48-day) oral administration of low-dose zearalenone (ZEA) resulted in changes in uterine histology in sexually immature gilts. The study involved 12 clinically healthy 2-month-old gilts with a determined immune status. The animals were randomly divided into two experimental groups (E1, n = 4; E2, n = 4) and a control group (C, n = 4). ZEA (20 μg/kg bw for group E1 and 40 μg/kg bw for group E2) was administered in gelatin capsules per os before the morning feeding for 48 days; group C was given placebo rather than ZEA. The animals were then sacrificed and the uteri were subjected to histological examination. Low doses of ZEA (50% and 100% of no observable adverse effect levels values) induced experimental hyperestrogenism and stimulated the proliferation of nearly all uterine wall tissues, as shown by significant increases in the index of proliferation values. The accompanying uterine hyperaemia caused uterine reddening and swelling. Atypical endometrial hyperplasia (hyperplasia simplex atypica) could be interpreted as the endometrium's physiological response to an excessive level of endogenous and/or exogenous estrogenic stimuli. The results of this study and the effects of ZEA in the uterus suggest that there is a possibility of detrimental health effects when the level of endogenous estrogens is low and the body is supplied with an additional dose of exogenous estrogens. Such effects probably results from synergic interaction that produce hyperestrogenism and lead to excessive estrogenic stimulation.     

Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy: the effect of vessel calibre

Pulmonary endarterectomy (PEA) is a curative therapeutic approach in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The location-dependent structural differences of thrombotic material found in pulmonary arteries in CTEPH are poorly investigated. We present the case of a 47-year-old woman with antiphospholipid syndrome, diabetes mellitus and abnormal fibrin phenotype, who underwent PEA for CTEPH. Intravascular material removed bilaterally during PEA (from lobar, segmental and sub-segmental arteries) has been studied using light and scanning electron microscopy (SEM). Light microscopy showed tighter fibrous network in the portions of intraluminal thrombotic material facing the vessel wall, which contained collagen and fibrin fibers, and abundant cells. Cells, evaluated by immunostaining, were present in the whole removed material. Tissue factor expression was also observed with the highest values in the portions of intravascular material facing the vessel wall. In the main pulmonary arteries, SEM images revealed thick fibers of fibrous proteins loosly meshed and few erythrocytes and platelets between them (both dysmorphic “wedged” and fresh cells were present). In the fibrotic layers, containing mainly collagen and fibrin, removed from the lobar/segmental pulmonary arteries we found a stepwise increase in fiber density with decreasing vessel calibre, followed by denser fibrous networks composed of thinner fibers. Elastic fibers in the lobar and segmental arteries were aligned along the blood flow vector. These findings demonstrate differences in the structure of endarterectomized PEA material dependent on the vessel calibre and might contribute to understanding of CTEPH pathophysiology.