Resveratrol and related compounds as antioxidants with an allosteric mechanism of action in epigenetic drug targets.

The present review is intended to focus on naturally occurring cytoprotective agents such as resveratrol (trans-3,4',5-trihydroxystilbene) and other related compounds, probably with similar molecular mechanisms of action and high capacity to find applications in medical fields. Several physiological aspects have been ascribed to resveratrol and similar compounds. Resveratrol, among others, has been recently described as a silent information regulator T1 (SIRT1) activator that increases AMP-activated protein kinase (AMPK) phosphorylation and reduces the oxidative damage biomarkers during aging in laboratory settings. The reports on resveratrol and other SIRT1 activators from various sources are encouraging. The pharmacological strategies for modulation of sirtuins by small molecules through allosteric mechanisms should gain a greater momentum including human research. Resveratrol and resveratrol-like molecules seem to fulfill the requirement of a new horizon in drug research since these molecules cover a growing research means as antioxidants with allosteric mechanism in epigenetic drug targets. However, one should keep in mind the challenges of extrapolation of basic research into clinical results. Overall, the issue of sirtuins in biology and disease provides an insight on therapeutic potentials of sirtuin-based therapeutics and demonstrates the high complexity of drug-targeting these modalities for human applications.

Differential oxidative stress responses to D-galactosamine-lipopolysaccharide hepatotoxicity based on real time PCR analysis of selected oxidant/antioxidant and apoptotic gene expressions in rat.

Oxidative stress and apoptosis are proposed mechanisms of cellular injury in studies of xenobiotic hepatotoxicity. This study is focused on addressing the mutual relationship and early signals of these mechanisms in the D-galactosamine and lipopolysaccharide (D-GalN/LPS) hepatotoxicity model, with the help of standard liver function and biochemistry tests, histology, and measurement of gene expression by RT-PCR. Intraperitoneal injection of 400 mg/kg D-GalN and 50 µg/kg LPS was able to induce hepatotoxicity in rats, as evidenced by significant increases in liver enzymes (ALT, AST) and raised bilirubin levels in plasma. Heme oxygenase-1 and nitric oxide synthase-2 gene expressions were significantly increased, along with levels of their products, bilirubin and nitrite. The gene expression of glutathione peroxidase 1 remained unchanged, whereas a decrease in superoxide dismutase 1 gene expression was noted. Furthermore, the significant increase in the gene expression of apoptotic genes Bid, Bax and caspase-3 indicate early activation of apoptotic pathways, which was confirmed by histological evaluation. In contrast, the measured caspase-3 activity remained unchanged. Overall, the results have revealed differential oxidative stress and apoptotic responses, which deserves further investigations in this hepatotoxicity model.

[Hemobilia].

The phenomenon now known as haemobilia was first recorded in XVII century by well known anatomist from Cambridge, Francis Glisson and his description was published in Anatomia Hepatis in 1654. Until today etiology, clinical presentation and management are clearly defined. Haemobilia is a rare clinical condition that has to be considered in differential diagnosis of upper gastrointestinal bleeding. In Western countries, the leading cause of haemobilia is hepatic trauma with bleeding from an intrahepatic branch of the hepatic artery into a biliary duct (mostly iatrogenic in origin, e.g. needle biopsy of the liver or percutaneous cholangiography). Less common causes include hepatic neoplasm; rupture of a hepatic artery aneurysm, hepatic abscess, choledocholithiasis and in the Orient, additional causes include ductal parasitism by Ascaris lumbricoides and Oriental cholangiohepatitis. Clinical presentation of heamobilia includes one symptom and two signs (Quinke triad): a. upper abdominal pain, b. upper gastrointestinal bleeding and c. jaundice. The complications of haemobilia are uncommon and include pancreatitis, cholecystitis and cholangitis. Investigation of haemobilia depends on clinical presentation. For patients with upper gastrointestinal bleeding oesophagogastroduodenoscopy is the first investigation choice. The presence of blood clot at the papilla of Vater clearly indicates the bleeding from biliary tree. Other investigations include CT and angiography. The management of haemobilia is directed at stopping bleeding and relieving biliary obstruction. Today, transarterial embolization is the golden standard in the management of heamobilia and if it fails further management is surgical.

[Ambulatory surgery of umbilical, epigastric and small incisional hernias: open preperitoneal flat mesh technique in local anaesthesia].

INTRODUCTION: The dilemma whether to use the mesh or non mesh technique in the management of umbilical, epigastric and small incisional hernia is slowly fading away. The open preperitoneal "flat mesh" technique performed as ambulatory surgery may be one of the solutions. THE AIM: The aim of this retrospective study is to present the results of open preperitoneal "flat mesh" technique in the management of umbilical, epigastric and small incisional hernia within MATERIAL AND METHODS: This study included 34 patients (11 of them with umbilical, 13 with epigastric and 8 of them with small incisional hernia) operated by one surgeon in the period January 2004-January 2006. RESULTS: The median operative time was 52 minutes for umbilical hernia's, 43 minutes for epgastric and 54 minutes for incisional hernia's. The ambulatory surgery was performed at 91% of patients. The median hospitalization was 4h for patients with umbilical hernia's, 3,7h for patients with epigastric and, 7,7h for patients with small incisional hernia. The follow up is 10,5 months. Apart of one superficial infection other complications were absent. CONCLUSION: The open preperitoneal "flat mesh" technique performed in local anesthesia as an ambulatory surgery provides good results in the management of umbilical, epigastric and small incisional hernia.

[Infection in hernia surgery].

Traditionally, the operation of hernia is considered as a clean operation due to expected, low incidence of infection, on the spot of surgical work (SSI). The incidence of SSI in hernia surgery is more frequent then it is assumed. The important risk factors for SSI are the following: type of hernia (inguinal, incisional), operative approach (open - laparoscopic), usage of the prosthetic material and drainage. Comparing to inguinal hernia repair, incisional hernia repair, is more frequently followed by the infection. The laparoscopic operations are followed with the lower incidence of SSI then in the case of open operations. The usage of the mesh does not increase the incidence of SSI, although the consequences of the mesh infection may be severe. A type I of the prosthesis is more resistant to the infection then prosthesis II and III. The mesh infection (type I) never involves its body but it is present around sutures and bended edges. The mesh infection Type II involves entire prosthesis while in the case of Type III it is present in its peripheral part. In the case of SSI, a prosthesis Type I is possible to be saved, while prosthesis Type II must be removed completely; and the same is for the Type III (the partial removal is rarely suggested). The defect that remained after excision of non-resorptive prosthesis is a long-term and very complicated surgical problem. In regard to the position of the mesh, SSI is more common if the mesh is placed subcutaneously then in the case of sub-aponeurotic premuscular, pre-aponeurotic retromuscular or pre-peritoneal mesh placemen. If the infection is present the nontension techniques using non-resorptive prosthetic implants are not recommended. The presence of drainage and its duration increases the incidence of SSI. It is more common for incisional hernioplasty then for inguinal hernia repair. If there is an indication for drainage it should be as short as possible. The cause of SSI for elective operations are bacteria's that arrives from the skin, while in the case of opening of various organs dominant bacteria's originate from them. The superficial infection does not lead to the recurrence, while it is very possible in the case for deep infection. There are no prospective studies that justify the usage of antibiotic prophylaxes in hernia surgery. The antibiotic prophylaxis is indicated for the clean operations when placing the implants and when severe complication is expected. The appearance of SSI increases the price of treatment and may lead to the recurrence.

[The Rives technique (direct inguinal approach) in treatment of large inguino-scrotal and recurrent hernias]. / Rivesova tenika (direktan ingvinalni pristup) u resavanju velikih ingvinoskrotalnih i recidivantnih kila.

In solving inguinal hernias, surgeons today have in front of them many variations of different operative procedures (both tensional and non-tensional techniques). They are performed through operative or endoscope approach. Classical tension techniques present the operation of choice for smaller indirect, direct or femoral hernias among younger patients while non/tensional techniques are the best solution for all types of inguinal hernia among older patients with big destruction of transversal fascia and the best solution for most of recurrent hernias. Positioning of mesh with non-tensional techniques can be completed on different levels, with big hernias where the biggest part of transversal fascia of miopectineal orifitium is destroyed it is anatomically the most useful to place the mesh in preperitoneal space. Rives technique is the base of that concept and it presents one of good solutions in that kind of situations. In the period January 2001 until december 2002 using different operative techniques the authors treated 99 inguinal hernias of which 78 were primary and 21 recurrent hernias. Rives technique was performed in 46 cases (46.5%) among which 26 cases were primary inguinoscrotal hernias (3 patients IIIA, 22 patients IIIB, 1 patient IIIC, according to Nyhus classification) and 20 cases were recurrent hernias (6 patients IVA, 11 IVB, 3 IVD). Complications after Rives technique were the following: 1 recurrence (2.17%), 1 ischemic orchitis (2.17%) and 1 scrotal hematoma (2.17%). Infections and chronic pain were not present. The follow up was from 30 days to 2 years. Authors have shown that Rives technique is reliable solution for primary indirect, direct and femoral hernias with big hernial defect (especially for big, so called "giant" inquinoscrotal hernias) and for all types of recurrent hernias. The advantage of the technique is an easy performance without some previous special training because of the fact that dissection and preparation is the same as for the tension techniques. With small amount of prosthetic material all weak points of miopectineal orifitium are closed. The real risks of this technique are ischemic orchitis and chronis neuralgia in treatment of recurrent hernias and the presence of polypropylene mesh in Bogras space.

[Modified Rives technic in the treatment of recurrent inguinal hernia]. / Modifikovana Rivesova tehnika u tretmanu recidivantnih ingvinalnih kila.

After the introduction of prosthetic material in hernia surgery the fundamental changes in operative strategy occurred. This is because the coverage of myopectineal orifitium with non-absorbable prosthesis decreases the incidence of recurrences. Because of the appearance of lateral re-recurrences after the classical Rives procedure, we modified the operative technique. The modified Rives technique consists of the following: always polypropilen mesh 15x10 cm; creation of the new internal inguinal ring between Poupart's ligament and mesh; no lateral notching the mesh and anchoring mesh 2-3 cm from the medial, inferior, lateral and superior edge. During the period January 2001-December 2003, 34 cases of recurrent hernias were operated on 7th dept. of I Surgical Clinic of CCS. The recurrences were managed by classical (10/34) or modified Rives technique through direct inguinal approach (22/34), less frequently Lichtenstein procedure (1/34) and McVay (1/34) technique. Among 10 patients with recurrent inguinal hernias managed by classical Rives technique 2 re-recurrences appeared (indirect and interstitial) and 2 cases of infection (immediately after the operation or 7 months after the operation), and in the group of 22 cases with recurrent inguinal hernias managed by modified Rives technique the aim complications didn't appear. Using the modified Rives technique we managed the primary hernias in 56 cases without recurrences and infections. The modified Rives technique, because of the way of mesh fixation (all around), no lateral notching of mesh and remaining hem in all directions secures abdominal wall protection 2-3 cm from the line of fixation and prevents any movement of the mesh. This procedure enables management of all inguinal hernias regardless to their size and full protection of the medial, femoral and lateral inguinal triangle. The modified Rives technique is the technique of choice for big multiple defects (giant inguino-scrotal and re-recurrences), especially among patients with increased intra-abdominal pressure when other techniques may be insufficient because of mesh protrusion.

[Elective resection of the spleen--overview of resection technics and description of a new technic based on radiofrequency coagulation and dessication]. / Elektivna resekcija slezine--pregled tehnika resekcije i prikaz nove tehnike zasnovane na radiofrekventnoj koagulaciji i desikaciji.

The authors present a short overview of the development of elective splenic resections. Past and present indications are presented. Contemporary hemostatic technique for elective splenic resection are discussed. An original new technique for transsegmental partial splenic resection using RF generator Radionic Cool Tip(without any aditional hemostatic procedures is presented. This technique is inovative and when use properly it is a practically zero blood loos technique. A patient with transsegmental splenic resection using RF generator is presented. Further clinical application of the technique is necessary.