Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats

BACKGROUND: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.     

The use of end-to-side nerve grafts to reinnervate the paralyzed orbicularis oculi muscle

Facial paralysis is a serious neurologic disorder, particularly when it affects the eye. Loss of the protective blink reflex may lead to corneal ulceration and, possibly, visual loss. The purpose of this study was to compare different nerve-grafting techniques to reanimate the paralyzed eyelid. Sixteen adult dogs (25 kg each) were allocated into four groups. Denervation of the left hemi-face was performed in all cases. One dog served as a control animal (group I). Group II dogs (n = 5) underwent end-to-side coaptation of the nerve graft to the intact palpebral branch and end-to-end coaptation to the denervated palpebral branch. Group III dogs (n = 5) underwent end-to-end coaptation of the nerve graft to the intact palpebral branch and end-to-end coaptation to the denervated palpebral branch. Group IV dogs (n = 5) underwent end-to-side coaptation of the nerve graft to the intact and denervated palpebral branches. The animals were monitored for 9 months after the surgical procedures, to allow adequate time for reinnervation. The dogs were postoperatively monitored with clinical observation, electrophysiologic testing, video motion analysis, and histologic assessments. Clinical observation and electrophysiologic testing demonstrated the production of an eye blink in the denervated hemi-face in all experimental groups. There was a trend toward increased speed of reinnervation for group III animals (end-to-end coaptations). It was concluded that end-to-side coaptation can produce a contralateral synchronous eye blink in a clinically relevant, large-animal model.     

Automated Detection of Soma Location and Morphology in Neuronal Network Cultures

Automated identification of the primary components of a neuron and extraction of its sub-cellular features are essential steps in many quantitative studies of neuronal networks. The focus of this paper is the development of an algorithm for the automated detection of the location and morphology of somas in confocal images of neuronal network cultures. This problem is motivated by applications in high-content screenings (HCS), where the extraction of multiple morphological features of neurons on large data sets is required. Existing algorithms are not very efficient when applied to the analysis of confocal image stacks of neuronal cultures. In addition to the usual difficulties associated with the processing of fluorescent images, these types of stacks contain a small number of images so that only a small number of pixels are available along the z-direction and it is challenging to apply conventional 3D filters. The algorithm we present in this paper applies a number of innovative ideas from the theory of directional multiscale representations and involves the following steps: (i) image segmentation based on support vector machines with specially designed multiscale filters; (ii) soma extraction and separation of contiguous somas, using a combination of level set method and directional multiscale filters. We also present an approach to extract the soma’s surface morphology using the 3D shearlet transform. Extensive numerical experiments show that our algorithms are computationally efficient and highly accurate in segmenting the somas and separating contiguous ones. The algorithms presented in this paper will facilitate the development of a high-throughput quantitative platform for the study of neuronal networks for HCS applications.     

DNA cleavage by homo- and heterotetranuclear Cu(II) and Mn(II) complexes with tetrathioether-tetrathiol moiety

Novel homotetranuclear Cu(II) and heteronuclear Cu(II)-Mn(II) complexes with tetrathioether-tetrathiol moiety have been prepared and their DNA relaxation activities with plasmid pCYTEXP (5kb) were electrophoretically established. The cleavage products analyzed by neutral agarose gel electrophoresis indicated that the interaction of the metal complexes with supercoiled plasmid DNA yielded linear, nicked or degraded DNA. The relaxation activities of both homo- and heterotetranuclear (SK4) complexes are time- and concentration-dependent. The findings suggest that SK4 with potent nucleolytic activity is a good nuclease substitute in the presence of cooxidant. Furthermore, the observation of induction of DNA into smaller fragments by SK4 is also significant.     

Physiological changes in them in post-stress emerging <Emphasis Type="Italic">Ctenanthe setosa</Emphasis> plants under drought conditions

The capability of Ctenanthe setosa (Rosc.) Eichler (Marantaceae), pre-exposed to severe drought stress, of adaptation to a new drought conditions was investigated. C. setosa unstressed plants were exposed to drought period of 70 days. These plants were named as primary-stress plants (PS). They were trimmed, and new plants were produced from their rhizomes. New growing plants were named as post-stress emerging (PSE) plants. It was observed that leaf area and petiole length of PSE plants were reduced, as compared to unstressed plants. When PSE plants were exposed to a second drought-stress cycle, it was determined that the degree of their leaf rolling was higher but their relative water content (RWC) was less than these parameters of PS plants during drought period. However, at the 81% rolling degree, RWC in PSE plants was higher than in PS plants. Consequently, it can be said that the PSE plant were more resistant to a new drought stress than unstressed and PS plants. In the leaves of PSE plants, which were exposed to a second drought-stress period, the content of soluble protein decreased in the early period of drought, but increased in the later periods. Also, the content of reducing sugar in PSE plants gradually decreased during the stress period. Proline content increased markedly during drought period, whereas peroxidase activity increased up to the 60th day and then decreased. This text was submitted by the authors in English.     

The effects of mesenchymal stem cell mitochondrial transplantation on doxorubicin‐mediated nephrotoxicity in rats

The effect of dysfunctional mitochondria in several cell pathologies has been reported in renal diseases, including diabetic nephropathy and acute kidney injury. Previous studies have reported that mitochondrial transplantation provided surprising results in myocardial and liver ischemia, as well as in Parkinson's disease. We aimed to investigate the beneficial effects of isolated mitochondria transplantation from mesenchymal stem cells (MSCs) in vivo, to mitigate renal damage that arises from doxorubicin‐mediated nephrotoxicity and its action mechanism. In this study, a kidney model of doxorubicin‐mediated nephrotoxicity was used and isolated mitochondria from MSCs were transferred to the renal cortex of rats. The findings showed that the rate of isolated mitochondria from MSCs maintains sufficient membrane integrity, and was associated with a beneficial renal therapeutic effect. Following doxorubicin‐mediated renal injury, isolated mitochondria or vehicle infused into the renal cortex and rats were monitored for five days. This study found that mitochondrial transplantation decreased cellular oxidative stress and promoted regeneration of tubular cells after renal injury (P < .001, P = .009). Moreover, mitochondrial transplantation reduced protein accumulation of tubular cells and reversed renal deficits (P = .01, P < .001). Mitochondrial transplantation increased Bcl‐2 levels, and caspase‐3 levels decreased in injured renal cells (P < .015, P < .001). Our results provide a direct link between mitochondria dysfunction and doxorubicin‐mediated nephrotoxicity and suggest a therapeutic effect of transferring isolated mitochondria obtained from MSCs against renal injury. To our knowledge, this study is the first study in the literature that showed good therapeutic effects of mitochondrial transplantation in a nephrotoxicity model, which is under‐researched.     

In vitro and in vivo activities of Haplophyllum myrtifolium against Leishmania tropica

This study aimed to evaluate the in vitro and in vivo leishmanicidal activity of an endemic Turkish plant and compare its efficacy with a reference drug. In addition to the in vitro activities of the ethanol, acidified and alkaloid extracts and furoquinoline alkaloids skimmianine and gamma-fagarine, in vivo antileishmanial activitiy of the acidified extract of Haplophyllum myrtifolium Boiss. (Rutaceae) were investigated against Leishmania tropica (L. tropica), a causative agent of cutaneous leishmaniasis. All the extracts and pure compounds showed in vitro inhibitory activity against the promastigotes of. L. tropica. The in vitro 50% inhibitory concentrations of y-fagarine, acidified extract, ethanol extract, skimmianine and alkaloid extract against promastigotes were determined as 8.7, 9.4, 10.9, 25.7 and 25.8 microg/ml respectively. In vivo results of Haplophyllum myrtifolium acidified extract showed that this plant has a limited effect on decreasing the lesion size of experimental mice infected with Leishmania tropica. To the best of our knowledge, this is the first time both the in vitro and in vivo antileishmanial activity of Haplophyllum mrytifolium have been reported in the same research.     

Serum Copper and Zinc Levels in Patients with Endometrial Cancer

Biological Trace Element Research - The aim of the present study was to evaluate serum concentrations of copper (Cu) and zinc (Zn), in relation with metabolic profile and clinicopathologic features...     

Salicylic acid pretreatment induces drought tolerance and delays leaf rolling by inducing antioxidant systems in maize genotypes

Salicylic acid (SA) acts as an endogenous signal molecule responsible for inducing abiotic stress tolerance in plants. In this study, the role of SA in improving drought tolerance in two maize cultivars (Zea mays L.) differing in their tolerance to drought was evaluated. The plants were regularly watered per pot and grown until the grain filling stage (R2) under a rainout shelter. At stage R2, parts of the plants were treated with SA, after which drought stress was applied. Leaf samples were harvested on the 10th and 17th days of the drought. Some antioxidant enzyme activity, such as the superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) content, was measured during the drought period. Exogenous SA prevented water loss and delayed leaf rolling in comparison with control leaves in both cultivars. As a consequence of drought stress, lipid peroxidation, measured in terms of malondialdehyde content, was prevented by SA. SA pretreatment induced all antioxidant enzyme activities, and to a greater extent than the control leaves, during drought. SA also caused a reduction in the ascorbate (ASC) and glutathione (GSH) content in two maize cultivars. The H₂O₂ level was higher in SA pretreated plants than the controls in both cultivars. Pretreatment with SA further enhanced the activities of antioxidant enzymes and the concentrations of non-enzymatic antioxidants in the tolerant cultivar compared with the sensitive cultivar. Results suggested that exogenous SA could help reduce the adverse effects of drought stress and might have a key role in providing tolerance to stress by decreasing water loss and inducing the antioxidant system in plants with leaf rolling, an alternative drought protection mechanism.     

Characterization of a thermoalkalophilic esterase from a novel thermophilic bacterium, Anoxybacillus gonensis G2

Poly-3-hydroxybutyrate (P3HB) degradation capabilities of a novel bacterium, Anoxybacillus gonensis G2, were investigated. Both changes on film surfaces of the solution-cast films monitored by scanning electron microscopy (SEM) and weight loss up to 24% after 72 h exposure to A. gonensis G2 cultures indicated secretion of an active esterase responsible for the degradation of P3HB films. Kinetic parameters, Vmax and Km for the esterase activity of crude enzyme from A. gonensis G2 in the presence of p-nitrophenylbutyrate as substrate were observed as 50 U/L and 0.125 mM, respectively, in 50 mM phosphate buffer, pH 7.5 at 60 degrees C. The stimulation of the activity by Ca2+ is an evidence for the requirement of Ca2+ as a cofactor for the enzyme activity which is a characteristic for lipases/esterases. Inhibition of the esterase activity by metal chelating agents such as ethylenediamine tetraacetate, azide and cyanide has also supported the requirement of a metal ion for the activity. The thermal and pH stability profiles for the enzyme showed that the thermophilic bacterium A. gonensis G2 secretes an extracellular thermoalkalophilic PHB depolymerase active at 60 degrees C, and stable at this temperature for 120 min at pH 7.5 and for 24 h at pH 7.5-9.5 range at 4 degrees C by retaining over 75% of its initial activities.