Uncovering the Role of Methylmercury on DNA Lesions at Cytotoxic Concentrations in Glutathione-Depleted Cells: Insights from Experimental and Computational Studies.

Organomercurials (RHg), especially methylmercury (MeHg) and ethylmercury (EtHg), are considered to be more neurotoxic than the inorganic counterpart (Hg). They cause massive DNA damage in cells, especially in neurons, where cellular glutathione (GSH) levels are significantly low. However, the mechanism by which RHg exerts massive DNA damage at cytotoxic concentrations in brain cells remains obscure.

Regulation of Tyrosinase Enzyme Activity by Glutathione Peroxidase Mimics.

Hydrogen peroxide plays a crucial role in the melanogenesis process by regulating the activity of the key melanin-forming enzyme tyrosinase, responsible for the browning of fruits, vegetables, and seafood. Therefore, a molecule with dual activities, both efficient tyrosinase inhibition and strong hydrogen peroxide degrading ability, may act as a promising antibrowning agent. Herein, we report highly efficient selone-based mushroom tyrosinase inhibitors and with remarkable glutathione peroxidase (GPx) enzyme-like activity.

Open Versus Laparoscopic Ventral Hernia Repair: A Randomized Clinical Trial.

Introduction With the advancement in technology as well as surgical techniques, laparoscopic ventral hernia repair (LVHR) is more commonly being performed as compared to open repair in various centres throughout the world. Our study aimed to compare the short-term operative outcomes between LVHR and open repair. Materials and methods Sixty patients diagnosed with noncomplicated ventral hernias were included in this prospective study and were randomly divided into the laparoscopic group and the open group.

Open Lichtenstein Hernioplasty Versus Laparoscopic Transabdominal Preperitoneal Mesh Repair: The Pain Factor.

Introduction One of the most commonly performed surgery by a general surgeon is inguinal hernia repair. There have been numerous open surgical techniques and two laparoscopic techniques described in the literature for the treatment of inguinal hernias. The treatment outcome of all these surgeries remains the same which is reducing the hernia and preventing recurrence.

Hg-C bond protonolysis by a functional model of bacterial enzyme organomercurial lyase MerB.

Herein, we report a novel synthetic compound 1, having a highly nucleophilic selenolate (Se) moiety and a thiol (-SH) functional group, which showed efficient Hg-C bond protonolysis of various R-Hg-X molecules including neurotoxic methylmercury and thimerosal, via direct -SH proton transfer to the highly activated C-atom of a departed R group with low activation energy barrier at room temperature (21 °C), in the absence of any external proton source and, thus, acts as a functional model of MerB.

Intravascular Thrombolysis Followed by Stenting as Management of Retrohepatic Inferior Vena Caval Thrombosis due to a Twist in the Inferior Vena Cava after Deceased Donor Liver Transplant.

Inferior vena cava (IVC) occlusion due to acute thrombosis is a rare but important vascular complication after deceased donor liver transplantation (DDLT) that has been reported to occur up to 2% of recipients in a posttransplant period. This may be caused by direct instrumentation of the IVC stenosis at the anastomotic site, haematoma, and rarely by a twist in the retrohepatic IVC. The location of the thrombus, the timing after the surgery, and associated hemodynamic disturbances define the outcome of the patient.

Role of Hydrogen Bonding by Thiones in Protecting Biomolecules from Copper(I)-Mediated Oxidative Damage.

The sulfur-containing antioxidant molecule ergothioneine with an ability to protect metalloenzymes from reactive oxygen species (ROS) has attracted significant interest in both chemistry and biology. Herein, we demonstrated the importance of hydrogen bonding in S-oxygenation reactions between various thiones and HO and its significance in protecting the metal ion from HO-mediated oxidation. Among all imidazole- and benzimidazole-based thiones (1-10), ImS (2) showed the highest reactivity toward HO-almost 10 and 75 times more reactive than N, N'-disubstituted ImS (5) and BzS (10), respectively.

Simultaneous voltammetric immunodetection of alpha-fetoprotein and glypican-3 using a glassy carbon electrode modified with magnetite-conjugated dendrimers.

The authors describe an electrochemical immunoassay for simultaneous determination of alpha-fetoprotein (AFP) and glypican-3 (GPC-3) which are important biomarkers for early detection of hepatocellular carcinoma (HCC). Magnetite (FeO) nanoparticles (NPs) were decorated with hyperbranched amino functionalized dendrimers. The modified NPs were coupled to the antibodies against AFP and GPC-3.

Copper-Driven Deselenization: A Strategy for Selective Conversion of Copper Ion to Nanozyme and Its Implication for Copper-Related Disorders.

Synthetic organic molecules, which can selectively convert excess intracellular copper (Cu) ions to nanozymes with an ability to protect cells from oxidative stress, are highly significant in developing therapeutic agents against Cu-related disorder like Wilson's disease. Here, we report 1,3-bis(2-hydroxyethyl)-1 H-benzoimidazole-2-selenone (1), which shows a remarkable ability to remove Cu ion from glutathione, a major cytosolic Cu-binding ligand, and thereafter converts it into copper selenide (CuSe) nanozyme that exhibits remarkable glutathione peroxidase-like activity, at cellular level of HO concentration, with excellent cytoprotective effect against oxidative stress in hepatocyte. Cu-driven deselenization of 1, under physiologically relevant conditions, occurred in two steps.

Cytoprotective effects of imidazole-based [S] and [S]-donor ligands against mercury toxicity: a bioinorganic approach.

Here we report the coordination behaviour of an imidazole-based [S1]-donor ligand, 1,3-dimethyl-imidazole-2(3H)-thione (L1), and [S2]-donor ligand, 3,3'-methylenebis(1-methyl-imidazole-2(3H)-thione) (L2) or 4,4'-(3,3'-methylenebis-(2-thioxo-2,3-dihydro-imidazole-3,1-diyl))dibutanoic acid (L3), with HgX2 (X = Cl, Br or I) in solution and the solid state. NMR, UV-Vis spectroscopic, and single crystal X-ray studies demonstrated that L1 or L2 coordinated rapidly and reversibly to the mercury center of HgX2 through the thione moiety. Treatment of L2 with HgCl2 or HgBr2 afforded 16-membered metallacycle k1-(L2)2Hg2Cl4 or k1-(L2)2Hg2Br4 where two Cl or Br atoms are located inside the ring.

Metal-free C(sp)-H functionalization of azoles: KCO/I-mediated oxidation, imination, and amination.

The direct C2-H oxidation and imination of a wide variety of azoles was achieved by using a commercially available simple K2CO3/I2 reagent combination. The iodinated azole adduct, produced via the in situ generation of N-heterocyclic carbene, is the key intermediate for C2-H oxidation, imination, and amination of azoles. Significantly, these reactions proceed under mild conditions with high to excellent yields, are scalable to large quantity and exhibit a broad substrate scope.

Protection of Endogenous Thiols against Methylmercury with Benzimidazole-Based Thione by Unusual Ligand-Exchange Reactions.

Organomercurials, such as methylmercury (MeHg ), are among the most toxic materials to humans. Apart from inhibiting proteins, MeHg exerts its cytotoxicity through strong binding with endogenous thiols cysteine (CysH) and glutathione (GSH) to form MeHgCys and MeHgSG complexes. Herein, it is reported that the N,N-disubstituted benzimidazole-based thione 1 containing a N-CH CH OH substituent converts MeHgCys and MeHgSG complexes to less toxic water-soluble HgS nanoparticles (NPs) and releases the corresponding free thiols CysH and GSH from MeHgCys and MeHgSG, respectively, in solution by unusual ligand-exchange reactions in phosphate buffer at 37 °C.

A Special Extract of Bacopa monnieri (CDRI-08) Restores Learning and Memory by Upregulating Expression of the NMDA Receptor Subunit GluN2B in the Brain of Scopolamine-Induced Amnesic Mice.

In the present communication, we have investigated effects of the CDRI-08, a well characterized extract of Bacopa monnieri, on expression of the GluN2B subunit of NMDAR in various brain regions of the scopolamine-induced amnesic mice. Our behavioral data reveal that scopolamine-treated amnesic mice exhibit significant decline in the spatial memory compared to the normal control mice. Our RT-PCR and immunoblotting data revealed that the scopolamine treatment resulted in a significant downregulation of the NMDAR GluN2B subunit expression in prefrontal cortex and hippocampus.

Development- and age-related alterations in the expression of AMPA receptor subunit GluR2 and its trafficking proteins in the hippocampus of male mouse brain.

AMPA type glutamate receptor (AMPAR) on the post synaptic membrane plays important role in the process of synaptic plasticity involving various scaffolding and trafficking proteins. However, their alterations during development- and aging are not well understood. Here, we report that the expression of AMPAR-GluR2 subunit is gradually up regulated in the hippocampus from 0 day to adult (20 week) and down regulated thereafter in 70 week old male mice.

Liver transplantatation- an overview.

Liver transplantation is a therapeutic option of choice for acute and chronic end-stage liver disease. Indications, contraindications, and surgical procedures for the liver transplantation have become well established. In most part of the world, the main source of liver for transplantation remains the donation after brain death (DBD), but in view of increasing death on the waiting list due to shortage of brain dead organs other options such as split liver transplantation, living donor liver transplantation (LDLT), and donation after cardiac death (DCD) have been used.

Vascular leiomyoma of foot.

Vascular leiomyomas of the foot are relatively rare benign soft tissue tumours which arise from the tunica media and present as painful or painless solitary subcutaneous nodules. We are reporting a rare case of vascular leiomyoma with a dystrophic calcification and a myxoid change.

Surgery in a patient with liver disease.

Surgery is often needed in patients with concurrent liver disease. The multiple physiological roles of the liver places these patients at an increased risk of morbidity and mortality. Diseases necessitating surgery like gallstones and hernia are more common in patients with cirrhosis.

Augmented macrophage differentiation and polarization of tumor-associated macrophages towards M1 subtype in listeria-administered tumor-bearing host.

This study investigates the effect of Listeria administration on differentiation of macrophages from precursor bone marrow cells and functional status of tumor-associated macrophages (TAM). Listeria administration not only resulted in an augmented infiltration of tumor by F4/80 macrophages but also repolarized the functional status of TAM displaying features of some M1 macrophage subtype with upregulated phagocytosis and tumoricidal activity accompanied by altered expression of monocarboxylate transporter-1, toll-like receptor-2, surface markers: CD11c, interleukin-2 receptor, CD62L, and secreted molecules: nitric oxide, interleukin (IL)-1, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor. Declined tumor cell survival and modulated repertoire of cytokines: interferon-γ, IL-6, IL-10, and transforming growth factor-β in tumor microenvironment indicated their role in polarization of TAM towards proinflammatory state.

Jejunal atresia associated with idiopathic ileal perforation.

Jejunoileal atresia is one of the common causes of neonatal intestinal obstruction. Intestinal perforation with meconium peritonitis in the neonatal period, which carries a high mortality rate, is also common. The association of jejunal atresia with idiopathic ileal perforation is very rare.

Haemolytic uraemic syndrome following acute pancreatitis.

Context: Haemolytic uraemic syndrome is a common cause of renal failure in children but it is a rare condition in adults. Acute pancreatitis in adult as a cause of haemolytic uraemic syndrome is very rare.

Case Report: A 19-year-old male presented with symptom and signs suggestive of acute pancreatitis which was confirmed as his serum amylase was significantly raised.

Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation -- a case report.

Aim: To report the use of radiofrequency ablation in the treatment of recurrent cholangiocarcinoma in the transplanted liver.

Methods: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after transplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.

Radiofrequency ablation of unresectable liver tumours.

Unresectable liver tumours have a dismal prognosis. Treatment with systemic or regional chemotherapy rarely results in a durable complete response. Radiofrequency ablation is a novel technique to achieve local destruction, which can be repeated and has been shown to be safe and effective.

An unusual case of haemobilia.

Arterio-biliary fistula is an uncommon cause of haemobilia. We describe a case of right hepatic artery pseudo-aneurysm causing arterio-biliary fistula and presenting as severe melaena and cholangitis. Gastroduodenoscopy failed to establish the exact source of bleeding and hepatic artery angiography and selective embolization of the pseudo-aneurysm successfully controlled the bleeding.