Meta-analysis of warmed versus standard temperature CO2 insufflation for laparoscopic cholecystectomy.

BACKGROUND: There is conflicting evidence for the use of warmed, humidified carbon dioxide (CO2) for creating pneumoperitoneum during laparoscopic cholecystectomy. Few studies have reported less post-operative pain and analgesic requirement when warmed CO2 was used. AIM: This systematic review and meta-analysis aims to analyse the literature on the use of warmed CO2 in comparison to standard temperature CO2 during laparoscopic cholecystectomy. METHODS: Systematic review and meta-analysis carried out in line with the PRISMA guidelines. Primary outcomes of interest were post-operative pain at 6 h, day 1 and day 2 following laparoscopic cholecystectomy. Secondary outcomes were analgesic usage and drop in intra-operative core body temperature. Standard Mean Difference (SMD) was calculated for continuous variables. RESULTS: Six randomised controlled trials (RCTs) met the inclusion criteria (n = 369). There was no significant difference in post-operative pain at 6 h [3 RCTs; SMD = -0.66 (-1.33, 0.02) (Z = 1.89) (P = 0.06)], day 1 [4 RCTs; SMD = -0.51 (-1.47, 0.44) (Z = 1.05) (P = 0.29)] and day 2 [2 RCTs; SMD = -0.96 (-2.30, 0.37) (Z = 1.42) (P = 0.16)] between the warmed CO2 and standard CO2 group. There was no difference in analgesic usage between the two groups, but pooled analysis was not possible. Two RCTs reported significant drop in intra-operative core body temperature, but there were no adverse events related to this. CONCLUSIONS: This review showed no difference in post-operative pain and analgesic requirements between the warmed and standard CO2 insufflation during laparoscopic cholecystectomy. Currently there is not enough high quality evidence to suggest routine usage of warmed CO2 for creating pneumoperitoneum during laparoscopic cholecystectomy.

Cytoprotective dibenzoylmethane derivatives protect cells from oxidative stress-induced necrotic cell death.

Screening of a small in-house library of 1863 compounds identified 29 compounds that protected Jurkat cells from hydrogen peroxide-induced cytotoxicity. From the cytoprotective compounds eleven proved to possess antioxidant activity (ABTS radical scavenger effect) and two were found to inhibit poly(ADP-ribosyl)ation (PARylation), a cytotoxic pathway operating in severely injured cells. Four cytoprotective dibenzoylmethane (DBM) derivatives were investigated in more detail as they did not scavenge hydrogen peroxide nor did they inhibit PARylation. These compounds protected cells from necrotic cell death while caspase activation, a parameter of apoptotic cell death was not affected. Hydrogen peroxide activated extracellular signal regulated kinase (ERK1/2) and p38 MAP kinases but not c-Jun N-terminal kinase (JNK). The cytoprotective DBMs suppressed the activation of Erk1/2 but not that of p38. Cytoprotection was confirmed in another cell type (A549 lung epithelial cells), indicating that the cytoprotective effect is not cell type specific. In conclusion we identified DBM analogs as a novel class of cytoprotective compounds inhibiting ERK1/2 kinase and protecting from necrotic cell death by a mechanism independent of poly(ADP-ribose) polymerase inhibition.

Protein kinase C protects from DNA damage-induced necrotic cell death by inhibiting poly(ADP-ribose) polymerase-1.

The goal of the current study, conducted in freshly isolated thymocytes was (1) to investigate the possibility that the activation of poly(ADP-ribose) polymerase-1 (PARP-1) in an intact cell can be regulated by protein kinase C (PKC) mediated phosphorylation and (2) to examine the consequence of this regulatory mechanism in the context of cell death induced by the genotoxic agent. In cells stimulated by the PKC activating phorbol esters, DNA breakage was unaffected, PARP-1 was phosphorylated, 1-methyl-3-nitro-1-nitrosoguanidine-induced PARP activation and cell necrosis were suppressed, with all these effects attenuated by the PKC inhibitors GF109203X or Gö6976. Inhibition of cellular PARP activity by PKC-mediated phosphorylation may provide a plausible mechanism for the previously observed cytoprotective effects of PKC activators.

Protein tyrosine nitration and poly(ADP-ribose) polymerase activation in N-methyl-N-nitro-N-nitrosoguanidine-treated thymocytes: implication for cytotoxicity.

1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) is a DNA alkylating agent. DNA alkylation by MNNG is known to trigger accelerated poly(ADP-ribose) metabolism. Various nitroso compounds release nitric oxide (NO). Therefore, we set out to investigate whether MNNG functions as NO donor and whether MNNG-derived NO or secondary NO metabolites such as peroxynitrite contribute to MNNG-induced cytotoxicity. MNNG in aqueous solutions resulted in time- and concentration-dependent NO release and nitrite/nitrate formation. Moreover, various proteins in MNNG-treated thymocytes were found to be nitrated, indicating that MNNG-derived NO may combine with cellular superoxide to form peroxynitrite, a nitrating agent. MNNG also caused DNA breakage and increased poly(ADP-ribose) polymerase activity and cytotoxicity in thymocytes. MNNG-induced DNA damage (measured by the comet assay) and thymocyte death (measured by propidium iodide uptake) was prevented by the PARP inhibitor PJ-34 and by glutathione (GSH) or N-acetylcysteine (NAC). The cytoprotection provided by PJ-34 against necrotic parameters was paralleled by increased outputs in apoptotic parameters (caspase activity, DNA laddering) indicating that PARP activation diverts apoptotic death toward necrosis. As MNNG-induced cytotoxicity showed many similarities to peroxynitrite-induced cell death, we tested whether peroxynitrite was responsible for at least part of the cytotoxicity induced by MNNG. Cell-permeable enzymic antioxidants (superoxide dismutase and catalase), the NO scavenger cPTIO or the peroxynitrite decomposition catalyst FP15 failed to inhibit MNNG-induced DNA breakage and cytotoxicity. In conclusion, MNNG induces tyrosine nitration in thymocytes. Furthermore, MNNG damages DNA by a radical mechanism that does not involve NO or peroxynitrite.

High Throughput Screening Identifies a Novel Compound Protecting Cardiomyocytes from Doxorubicin-Induced Damage.

Antracyclines are effective antitumor agents. One of the most commonly used antracyclines is doxorubicin, which can be successfully used to treat a diverse spectrum of tumors. Application of these drugs is limited by their cardiotoxic effect, which is determined by a lifetime cumulative dose. We set out to identify by high throughput screening cardioprotective compounds protecting cardiomyocytes from doxorubicin-induced injury. Ten thousand compounds of ChemBridge's DIVERSet compound library were screened to identify compounds that can protect H9C2 rat cardiomyocytes against doxorubicin-induced cell death. The most effective compound proved protective in doxorubicin-treated primary rat cardiomyocytes and was further characterized to demonstrate that it significantly decreased doxorubicin-induced apoptotic and necrotic cell death and inhibited doxorubicin-induced activation of JNK MAP kinase without having considerable radical scavenging effect or interfering with the antitumor effect of doxorubicin. In fact the compound identified as 3-[2-(4-ethylphenyl)-2-oxoethyl]-1,2-dimethyl-1H-3,1-benzimidazol-3-ium bromide was toxic to all tumor cell lines tested even without doxorubicine treatment. This benzimidazole compound may lead, through further optimalization, to the development of a drug candidate protecting the heart from doxorubicin-induced injury.

Appendiceal faecaliths are associated with right iliac fossa pain.

INTRODUCTION: There is debate over whether a normal-looking appendix should be removed at diagnostic laparoscopy performed for right iliac fossa (RIF) pain. Faecaliths are associated with appendicitis. This study assessed whether there was an association between the removal of normal appendices containing faecaliths and improvement of symptoms. PATIENTS AND METHODS: Analysis of the histology database for all appendicectomies during 2003-2007 with normal histology, noting presence of a faecalith. Retrospective study using a telephone questionnaire for frequency/duration of pre-operative symptoms, postoperative symptom recurrence, re-admission rates and complications. The faecalith-positive (f(+)) group was compared to a similar control group of patients who had a normal appendix removed which did not contain a faecalith (f(-)). RESULTS Out of 203 appendicectomies performed with normal histology, 26 (13%) were f(+). Of these, 21 responded to the questionnaire. Thirty-one consecutive patients with normal histology and no faecalith were identified. A similar proportion in each group presented with three or more episodes of pain prior to appendicectomy (38% f(+); 39% control). Only one (5%) of the f(+) patients had recurring symptoms after the operation, compared with 14 (48%) of the control group (P = 0.0016). Only one (5%) of the f(+) patients underwent further investigations, compared with 11 (36%) of the control group (P < 0.02). None of the f(+) patients were re-admitted, compared to 19% of the control population. There were no significant postoperative complications in either group. CONCLUSIONS: Appendiceal faecaliths may be a cause of right iliac fossa pain in the absence of obvious appendiceal inflammation. In this study, the policy of routine removal of a normal-looking appendix at laparoscopy in the absence of any other obvious pathology appeared to be an effective treatment for recurrent symptoms in those cases with a faecalith. Further studies are needed to assess this putative association.

Genetic ablation of PARP-1 protects against oxazolone-induced contact hypersensitivity by modulating oxidative stress.

Contact hypersensitivity (CHS) reaction is a form of delayed-type of hypersensitivity caused by contact allergens such as oxazolone (OXA). In previous studies it has been shown that poly(ADP-ribose) polymerase (PARP) inhibition reduces the extent of inflammation in CHS. We aimed to shed light on the molecular events causing the protective effect of PARP inhibitors. PARP-1 and -2 knockout mice were sensitized by abdominal delivery of OXA, and a week later CHS was induced by applying OXA on the ears of the mice. PARP-1(-/-) mice were protected against OXA-induced CHS in contrast to PARP-2(-/-) mice. In PARP-1(-/-) mice, neutrophil infiltration was reduced in line with the suppressed expression of proinflammatory cytokines, cell adhesion factors, and matrix metalloproteinase-9, which is likely because of impaired activation of NF-κB p65 and activating transcription factor-2, the two redox-sensitive transcription factors. Moreover, reduced nitrosative and oxidative stress was observed under inflammatory conditions in the PARP-1(-/-) mice when compared with PARP-1(+/+). In conclusion, PARP-1 activation is necessary for proinflammatory gene expression through which PARP-1 enhances neutrophil infiltration and hence oxidative/nitrosative stress, forming a vicious circle, and further aggravating the inflammatory process. Our data identify PARP-1 as a possible target in CHS.

Strangulated inguinal hernia due to an omental band adhesion within the hernial sac: a case report.

INTRODUCTION: Strangulated Inguinal hernia is one of the most common surgical emergencies dealt with by surgeons worldwide. Usually the narrow internal inguinal ring or the external inguinal ring is the site of constriction of the viscus, which forms the content of the hernia resulting in strangulation. We report a rare case of strangulated inguinal hernia where the constricting element is not the internal or external inguinal ring, but an omental band adhesion causing closed loop small bowel obstruction and gangrene within the hernial sac in the inguinal canal. CASE REPORT: A 56-year-old Caucasian gentleman presented to us with a 6 hours history of non-reducible tender lump in his right groin. His groin was explored urgently under general anaesthesia and was found to have an omental band adhesion causing closed loop small bowel obstruction with gangrene within the hernial sac in the inguinal canal with a wide internal inguinal ring. Gangrenous small bowel was resected and primary anastomosis was performed through the same inguinal incision. CONCLUSION: Strangulation of the inguinal hernial content is usually due to the tight constriction at the level of internal inguinal ring or at external inguinal ring. Uncommonly strangulation of the contents can occur due to other causes like omental band adhesion. Anyone presenting with clinical features of strangulated inguinal hernia with small bowel obstruction mandates prompt exploration of the inguinal canal. Although it may not change the treatment approach, one should be aware about this special entity. Resection of the gangrenous small bowel and primary anastomosis can be safely performed through the same inguinal incision.

Torsion of parietal-peritoneal fat mimicking acute appendicitis: a case report.

INTRODUCTION: Infarctions of the greater omentum and appendices epiploicae are uncommon, but well documented causes of acute abdominal pain. We present a rare case of torted fat on the parietal peritoneum over the anterior abdominal wall, mimicking clinical signs of acute appendicitis, which was diagnosed at laparoscopy. We are aware of only two other similar reported cases, both of which were diagnosed at the time of laparotomy. CASE PRESENTATION: A 41-year-old Caucasian woman presented with clinical signs of acute appendicitis. On diagnostic laparoscopy, a non-inflamed appendix was found. Further exploration revealed a necrotic torted appendage of fat overlying the parietal peritoneum of the right iliac fossa of the anterior abdominal wall. CONCLUSION: Torted fatty appendages can be a diagnostic dilemma often mimicking more common causes of an acute abdomen. Laparoscopy is an excellent tool making the correct diagnosis in such cases.