The effects of exogenous l-carnitine on lipid peroxidation and tissue damage in an experimental warm hepatic ischemia-reperfusion injury model

Background:l-Carnitine is the essential endogenous factor for the transport of long-chain fatty acids from the cytoplasm to within the mitochondrion where the β-oxidation process takes place. l-Carnitine is a superoxide scavenger and an antioxidant that possesses an anti-ischemic action and a stabilizing effect on cell membranes. It may be of help in liver ischemia reperfusion injury. Results regarding the effects of l-carnitine on liver ischemia and reperfusion injury are few and conflicting.Objective: The aim of this study was to investigate the efficacy of exogenous l-carnitine on lipid peroxidation and protecting liver at different stages of experimental total warm hepatic ischemia-reperfusion (TWHIR) procedure in rats.Methods: This experimental study in healthy, weanling, male Wistar rats (weighing 180-200 g) was conducted at the Experimental Animal Research Laboratory of the Faculty of Medicine of Mersin University, Mersin, Turkey. Rats were randomly divided into 5 groups: (A) Control group; (B) TWHIR procedure only; (C) l-carnitine administered 2 hours before the TWHIR procedure; (D) l-carnitine administered just before the TWHIR procedure; and (E) l-carnitine administered after total warm hepatic ischemia but just before the reperfusion procedure. Total warm hepatic ischemia (via the Pringle maneuver) and reperfusion were performed for 45 and 30 minutes, respectively. l-Carnitine (200 mg/kg) was administered intravenously. At the end of each procedure a blood sample was drawn and total hepatectomy was performed following reperfusion. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels of both plasma and liver tissue, total antioxidant capacity (TAOC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma, and histopathologic examination were analyzed to assess lipid peroxidation and damage in liver tissue.Results: Thirty-four rats (mean [SD]age, 59.26 [1.2]days; mean [SD] weight, 194.1 [5.1] g) were used in the study. There was a significant difference observed between groups A (n = 5) and B (n = 5) for all evaluation parameters. The TWHIR procedure performed in group B was associated with significant increases versus baseline in ALT, AST, MDA, and MPO in plasma, and MDA and MPO in liver tissue, but a significant decrease of TAOC in plasma. ALT, AST, serum and liver MDA, and MPO levels of group B were significantly higher than all groups administered l-carnitine. l-Carnitine administration between total warm hepatic ischemia and reperfusion was associated with a significant attenuation in all parameters. The liver MDA levels of groups C (n = 8) and D (n = 8) were significantly lower than that of group E (n = 8) (mean [SD]: C, 16.53 [3.32] and D, 18.28 [1.67] vs E, 23.05 [3.52]; P = 0.001 and P = 0.016, respectively). The mean (SD) liver MPO level of group C (1.09 [0.16]) was significantly lower than that of groups D (2.12 [0.25]) and E (2.11 [0.28]) (both, P = 0.001). The TAOC of group B (0.77 [0.12]) was significantly lower than that of groups C (1.34 [0.19]) and D (1.08 [0.20]) (P = 0.001 and P = 0.015, respectively). The TAOC of group C was significantly higher than that of the other l-carnitine groups (E, 0.94 [0.13]) (P = 0.023 vs group D; and P = 0.001 vs group E). Histopathologic scores of groups A, C, and E were significantly lower than that of group B, but the difference between groups B and D was not statistically significant.Conclusions: In this experimental study, administration of exogenous l-carnitine was associated with significantly decreased lipid peroxidation in plasma and liver tissue when administered prior to a TWHIR procedure. In addition, l-carnitine seemed to be more effective with regard to decreasing lipid peroxidation in liver tissue when administered before warm hepatic ischemia. l-Carnitine was associated with significantly decreased leukocyte sequestration in plasma and liver tissue. A significant increase in TAOC was associated with l-carnitine administered prior to ischemia. These observations suggest that l-carnitine might have a protective effect against ischemia-reperfusion injury in rat liver tissue.     

N-acetylcysteine enhances multidrug resistance-associated protein 1 mediated doxorubicin resistance

BACKGROUND: Resistance of cancer cells against anticancer agents is caused partly by multidrug resistance-associated protein 1 (MRP1). The exact mechanism of MRP1-involved multidrug resistance has not yet been clarified, although glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-buthionine (S,R)-sulfoximine (BSO) inhibits GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated doxorubicin resistance in human embryonic kidney (HEK293) and its MRP1-transfected 293MRP cells. MATERIALS AND METHODS: Human embryonic kidney cells were transfected with a plasmid encoding the whole MRP1 gene. Both cells were incubated with doxorubicin in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. Glutathione, glutathione S-transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. RESULTS: N-acetylcysteine increased the resistance of both cells against doxorubicin. DL-buthionine (S,R)-sulfoximine decreased NAC-enhanced MRP1-mediated doxorubicin resistance, indicating that induction of MRP1-mediated doxorubicin resistance depends on GSH synthesis. Doxorubicin decreased the cellular GSH concentration and increased GPx activity. Glutathione S-transferase activity was decreased by NAC. CONCLUSION: Our results demonstrate that NAC enhances MRP1-mediated doxorubicin resistance and this effect depends on GSH synthesis. DL-buthionine (S,R)-sulfoximine seems a promising chemotherapy improving agent in MRP1 overexpressing tumour cells.     

Recovery of conduction disorders after sutureless aortic valve replacement

 Open in a separate windowOBJECTIVESConduction disorders and the need for permanent pacemaker (PPM) implantation after surgical aortic valve replacement are well-recognized complications. However, in the case of sutureless valve prostheses, it remains unknown whether pacemaker (PM) dependency and conduction disturbances resolve over time. Our aim was to evaluate whether conduction disorders after Perceval sutureless valve implantation recover during follow-up. METHODSPatients undergoing isolated surgical aortic valve replacement or concomitant aortic valve replacement with coronary artery bypass surgery using the Perceval sutureless valve, between January 2010 and July 2018, were included. Postoperative electrocardiogram findings were analysed to determine the incidence of new-onset left bundle branch blocks (LBBBs) and the requirement for PPM implantation. During a postoperative period of 6–18 months, electrocardiogram findings during PM checks were analysed to determine PM dependency and LBBB persistence.RESULTSOut of 184 patients who received a Perceval prosthesis during the study period, 39 (21.2%) patients developed new-onset LBBB and 10 patients (5.4%) received a PPM postoperatively. The occurrence of conduction disorders was not associated with valve size. Follow-up was completed in 176 (95.7%) patients. In patients with a new-onset LBBB, 35.9% recovered during follow-up (P = 0.001). Seven out of 10 (70%) patients remained PM dependent.CONCLUSIONSAfter Perceval aortic valve implantation, new-onset LBBB recovers in more than one-third of patients during follow-up. In patients who needed a postoperative PPM, the majority remained PM dependent.     

Development and characterization of rapid dissolving ornidazole loaded PVP electrospun fibers

Gingivitis is a common and mild form of periodontal disease and can be described as a limited inflammation of the gingiva. This study aims to develop and characterize rapid releasing mucoadhesive fibers containing ornidazole with electrospinning process for the treatment of gingivitis. Polyvinylpyrrolidone (PVP) was chosen as a polymer and used at different concentrations of 10%, 12.5%, and 15%. Scanning electron microscopy images showed that fiber diameters increased with increasing polymer concentrations. Tensile strength and elongation at break values of fibers increased with increasing PVP amount, whereas the loading of ornidazole into the fibers decreased these parameters. The contact angle values of all fibers were found to be 0° due to the hydrophilic nature of PVP. Ornidazole was released within 5?min and diffused from all of the fibers faster than that of gel and solution formulations. Electrospun ornidazole fibers were found efficient against Porphyromonas gingivalis in antimicrobial activity studies. The results demonstrated that ornidazole loaded fibers could be a potential drug delivery system for the treatment of gingivitis.     

Single square hemostatic suture for postpartum hemorrhage secondary to uterine atony

Objective

The objective of this study is to describe a novel technique for the treatment of postpartum hemorrhage and evaluate its effectiveness and safety.

Methods

Single square hemostatic suture was performed for uterine atony when postpartum hemorrhage did not respond to medical therapy and bilateral uterine artery ligation. We retrospectively reviewed the data of 11 women and evaluated their endometrial cavity with hydrosonography after a follow-up period of 8–34 months.

Results

The single square hemostatic suture successfully stopped bleeding in all of the cases. Of the 11 women, 2 could not be traced. Menstruation started without delay in nine women. One of the women achieved pregnancy 25 months after surgery. The six women who underwent hydrosonography had an intact endometrial cavity.

Conclusions

For women who desire future fertility, and when bilateral uterine artery ligation is not sufficient to control PPH, single square suturing may be used as an effective and safe procedure.     

A morphological and micro-tensile bond strength evaluation of a single-bottle adhesive to caries-affected human dentine after four different caries removal techniques

OBJECTIVES: This study evaluated the influence of different caries removal techniques (conventional bur; chemomechanical removal/Carisolv()-MediTeam; a sonic preparation system/SonicsysMicro-Kavo and air abrasion/PrepStar-Danville Engineering) on microtensile bond strength to caries-affected human dentine. METHODS: Occlusal surfaces of extracted human permanent third molars with coronal dentine caries extending approximately halfway through the dentine was ground perpendicular to the long axis of the tooth to expose a flat surface of normal dentine surrounding the carious lesion with laser fluorescence values of approximately 30 (DIAGNODent), KaVo). Carious lesions were excavated with one of the four techniques until laser fluorescence values decreased to 15 in the center of the lesions. An ethanol-based dentine adhesive (Single Bond, 3M) was used to bond composite resin (P60, 3M) to the substrate. Vertical slices (n=11/group), approximately 0.8 mm thick were made through the caries-affected portions of each tooth, perpendicular to the bonding surface. Specimens were subjected to tensile stress at a crosshead speed of 1 mm/min. Data were analyzed by Kruskal-Wallis test. SEM investigation was performed for the qualitative evaluation of resin-dentine hybridization. RESULTS: The microtensile bond strengths were as follows (mean+/-SD in MPa): 6.4+/-5.3 (bur), 8.4+/-3.3 (Carisolv), 8.5+/-5.9 (Sonicsys Micro), and 8.8+/-8.8 (air abrasion). Statistical analysis did not show significant differences between any of the treatment modalities (p=0.160). Tensile fracture was cohesive within caries-affected dentine in all specimens. CONCLUSIONS: The four different caries removal techniques used within this study did not influence the bond strength of the tested dentine adhesive to caries-affected human dentine.     

Role of Radial Endosonography in the Diagnosis of Acute Cholangitis

Background and Study Aim  

We aimed to assess radial endoscopic ultrasound (EUS) features of the bile duct wall as well as biliary luminal liquid characteristics in cases with acute cholangitis.