Extracellular Histones H3 as a Prognostic Blood Marker for Delayed Liver Function Recovery After Donor Hepatectomy.

BACKGROUND: Early prediction of liver dysfunction after liver resection remains a challenge. We hypothesized that extracellular histone concentrations are a promising new biomarker for the detection of liver injury after donor hepatectomy. METHODS: This prospective study considered 93 living donors who underwent hepatectomy. Blood samples of donors were collected on postoperative day 1, and histone levels in the plasma samples of the patients were measured with total histone H3 sandwich ELISA kits. Among 86 right lobe donors, 23 (26.7%) were deemed to have a delayed liver function recovery according to the International Study Group of Liver Surgery's definition of posthepatectomy liver failure, whereas 63 (73.3%) were considered to have an adequate liver function recovery. RESULTS: The area under the receiver operating characteristic (ROC) curve for circulating histones in predicting persistent liver dysfunction was 0.618 ± 0.06 (95% confidence interval [CI], 0.501-0.735; P = .091). The cutoff point value obtained from the analysis of ROC curves was 0.895, with a sensitivity of 95.7% and a specificity of 32.9%, respectively, for examining a delayed liver function recovery (P = .015). The Fisher analysis significantly verified these results empirical influence function % 7.90 (95% CI, 3.91-11.90; P = .006). The univariate analysis determined that postoperative histones were identified as an independent risk factor of delayed liver function recovery (odds ratio, 10.8; 95% CI, 1.4-84.9; P = .024). CONCLUSIONS: The circulating histone negatively correlates with liver dysfunctions after donor hepatectomy and had the best value in predicting liver dysfunction within 24 hours after liver resection.

In vitro characterization and endocrine regulation of cholesterol and phospholipid transport in the mammary gland.

Cell-based studies previously showed that the ATP-binding cassette transporter A1 (ABCA1) transfers cholesterol across mammary epithelial cells (MEC). Data for phospholipid transport are lacking, and it is unclear from which cellular source the transported cholesterol stems, whether this transport activates signaling pathways, and how lactogenic hormones regulate it. To clarify these aspects, lipid transport and expressional analyses were performed in bovine primary (bMEC) and/or immortalized (MAC-T) MEC cultures. Lipid efflux and ABCA1, ABCG1 and liver X receptorα mRNA levels were higher in MAC-T than bMEC. In MAC-T, the transported cholesterol originated mainly from the plasma membrane. ABCA1 dependent cholesterol efflux was higher than phosphatidylcholine efflux, was suppressed by probucol (ABCA1 inhibitor), AG490 (janus kinase-2 inhibitor), PD98059 (mitogen activated protein kinase kinase inhibitor) and pretreatment with ß-cyclodextrin (lowering membrane cholesterol). Insulin was the only hormone significantly increasing cholesterol efflux. In conclusion, this study gives novel mechanistic and regulatory insights into the transport of cholesterol and phospholipids in MEC.

Hypoxic treatment of human dual placental perfusion induces a preeclampsia-like inflammatory response.

Preeclampsia is a human pregnancy-specific disorder characterized by a placental pro-inflammatory response in combination with an imbalance of angiogenic factors and clinical symptoms, including hypertension and proteinuria. Insufficient uteroplacental oxygenation in preeclampsia due to impaired trophoblast invasion during placentation is believed to be responsible for many of the molecular events leading to the clinical manifestations of this disease. We investigated the use of hypoxic treatment of the dual placental perfusion system as a model for preeclampsia. A modified perfusion technique allowed us to achieve a mean soluble oxygen tension within the intervillous space (IVS) of 5-7% for normoxia and <3% for hypoxia (as a model for preeclampsia). We assayed for the levels of different inflammatory cytokines, oxidative stress markers, as well as other factors, such as endothelin (ET)-1 that are known to be implicated as part of the inflammatory response in preeclampsia. Our results show a significant increase under hypoxia in the levels of different inflammatory cytokines, including IL-6 (P=0.002), IL-8 (P<0.0001), TNF-α (P=0.032) and IFN-γ (P=0.009) at 360 min in maternal venous samples (n=6). There was also a significant increase in ET-1 levels under hypoxia both on the maternal side at 30 min (P=0.003) and fetal side at 360 min (P=0.036) (n=6). Other markers of oxidative stress, including malondialdehyde and 8-iso-protaglandin F2α (P=0.009) also show increased levels. Overall, these findings indicate that exposure of ex vivo dually perfused placental tissue to hypoxia provides a useful model for mimicking the inflammatory response characteristic of preeclampsia. This would therefore provide a powerful tool for studying and further delineating the molecular mechanisms involved in the underlying pathophysiology of preeclampsia.

[En route in Switzerland - tick-borne and hantavirus infections]. / Unterwegs in der Schweiz - von Menschen, Mäusen und Zecken.

Tick-borne infections are endemic in Switzerland with borreliosis being the most frequent one, followed by the vaccine-preventable tick-borne encephalitis and more rarely by anaplasmosis, rickettsioses and babesiosis. Short characteristics of these infections are presented. The main preventive measures for stays in endemic regions include not leaving forest tracks and wearing closely fitted clothes and shoes, impregnated with an insecticide. Following at-risk activities, clothes as well as the body should be searched for ticks and they have to be removed using a tick removing tool. The body area of the tick bite has to be observed and a physician visit is strongly urged in case of rising fever and/or of erythema migrans. Hantavirus infections: Nephropathia epidemica is a zoonosis caused by the Puumala type of hantavirus and transmission occurs by inhaling aerolized excretions of the bank vole. There is no known human to human transmission. The incidence of this infection varies in a cyclic fashion and typical clinical symptoms include sudden onset of fever, headache, abdominal and back pain and transient renal impairment with initial oliguria and later polyuria. At-risk activities include camping and cleaning of rodent infestations. In these cases, face masks should be worn and the excretions be moistened before cleaning is started. In Germany, 2 - 3 years-cycles of outbreaks were observed between 2005 and 2012 with regional clusters approaching Switzerland. Therefore, disease awareness of physicians and infection surveillance are essential.

Vascular endothelial growth factor (VEGF) levels of gingiva and gingival crevicular fluid in diabetic and systemically healthy periodontitis patients.

It has been demonstrated that diabetes mellitus (DM) may have an inductive effect on the vascular endothelial growth factor (VEGF) levels of periodontium during periodontal disease. The aim of this study is to confirm this phenomenon, investigating whether it is also valid for diabetic periodontitis patients under good metabolic control. Sixteen type II DM patients, all with a glycosylated hemoglobin (HbA1c) value less than 7 (test), and 15 systemically healthy (control) chronic periodontitis patients were included in the study. The VEGF concentrations in the gingival supernatants and gingival crevicular fluid (GCF) samples of the study groups were measured by enzyme-linked immunosorbent assay. The data were analyzed by Student's t test in statistical means. The VEGF levels were significantly higher in the gingival supernatants of the test group (55.89 +/- 8.11 pg/ml) than that of the control group (24.81 +/- 2.04 pg/ml; p < 0.01). However, there was no statistically significant difference in the VEGF levels of GCF between the study groups (38.96 +/- 4.89 pg/ml in the test and 32.20 +/- 4.02 pg/ml in the control group; p > 0.05). Our study confirms that DM affects the VEGF levels of periodontal soft tissues in periodontal disease, and our results also suggest that this effect may not be influenced by the metabolic control of DM.

Increased expression of vascular endothelial growth factor in cyclosporin A-induced gingival overgrowth in rats.

BACKGROUND: Gingival overgrowth is a side effect associated with cyclosporin A (CsA) therapy. The lesion is characterized by increased epithelial thickness, enlargement of connective tissue, and increased vascularization. The aim of this experimental study was to examine the role of vascular endothelial growth factor (VEGF) in the pathogenesis of CsA-induced gingival overgrowth. METHODS: Twenty male Wistar rats were divided into two groups of 10 animals each. For the development of gingival overgrowth, one group received CsA therapy subcutaneously in a daily dose of 10 mg/kg for 60 days, and the other group was used as a control. At the end of the experimental period, rats were subsequently decapitated, and the mandibles with the surrounding gingiva and soft tissue were removed. Half of each sample was used for histomorphometric analysis, and the other half was used for biochemical analysis. Histomorphometric analysis included the measurements of the number and diameter of blood vessel profiles under a microscope, and biochemical analysis included the assessment of VEGF concentration by enzyme-linked immunosorbent assay (ELISA). RESULTS: The histomorphometric findings showed that the number of blood vessel profiles increased in the CsA group compared to the control group (P <0.001), although the increase in the diameter of blood vessel profiles was not significant (P >0.05). The biochemical findings showed that in vivo VEGF expression was higher in the CsA group compared to the control group (P <0.001). CONCLUSION: The results of this study suggest that increased VEGF expression may be associated with the pathogenesis of CsA-induced gingival overgrowth.

Reactive oxygen species scavenging activity during periodontal mucoperiosteal healing: an experimental study in dogs.

Excessive release of reactive oxygen species (ROS) in wounded tissue due to inflammation and ischaemia is a deleterious and destructive phenomenon for the healing process. Hence, scavenging of ROS is one of the essential steps in normal wound repair. In this study, we presented a profile of free radical scavenging enzyme (FRSE) activity of periodontal mucoperiosteal wounds in order to investigate ROS activity during periodontal wound healing. Mucoperiosteal periodontal flaps were elevated in the mandibular buccal region of seven dogs between the first premolar and first molar teeth, creating acute incisional wounds in the inner side of the flaps and they were replaced 30 min after elevation. Gingival samples taken from certain biopsy regions at baseline (before flap elevation), day 3, 12, 21 and 30 were processed for detection of active amounts of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). All enzyme activities had increased by more than 100% of their baseline levels by day 3. SOD activity decreased gradually from days 3 to 30 and reached a level lower than the baseline value. The increase in CAT activity continued until day 21, and decreased to a level higher than the baseline value by day 30. GPX also decreased from day 3, and reached a level less than its baseline value by day 30. Our results suggest that FRSEs may contribute to the detoxification of ROS during periodontal mucoperiosteal healing. This relationship may be utilized to facilitate soft tissue and/or flap management in periodontal or intra-oral treatments.

The effect of polylactide membranes on the levels of reactive oxygen species in periodontal flaps during wound healing.

It is consented that reactive oxygen species (ROS) are deleterious to wound healing process due to the harmful effects on cells and tissues. Absorbable synthetic biomaterials are considered to be degraded via ROS. Free-radical-scavenging enzymes (FRSE) are a cytoprotective enzymal group that has an essential role in the reduction, de-activation and removal of ROS as well as regulating wound healing process. In the present study, synthetic and absorbable polylactide (PLA) barrier membranes were evaluated by means of ROS activity levels during degradation in the healing periodontal flaps measuring the activity of FRSE superoxide dismutase (SOD) and catalase (CAT). Gingival biopsies taken from 10 patients allowing both guided tissue regeneration (test) and conventional flap surgery (control) before and 1 month after the operations were processed and the supernatants were studied by Mc Cord and Fridovich, Flohe and Otting, and Luck methods to measure total SOD and CAT levels respectively. A significantly increased enzyme activity of SOD and CAT was observed in both groups (p<0.05). SOD activity change was 62.92% in the test and 3.97% in the control group, and, CAT activity change was 48.04% in the test and 11.58% in the control group. Our results suggest that ROS, particularly superoxide anions, may contribute to the degradation phase of PLA membranes and this may affect the wound healing of periodontium at least for one-month period.