This has been observed after accidental injuries with nonsterile needles29

or in chimpanzee studies.16 Two conclusions can be drawn from these observations: (1) the majority of the genome containing HBV and HDV particles is infectious; (2) HBV and HDV must have evolved a mechanism that efficiently promotes them to the liver. The molecular basis for this liver tropism is unknown. The work presented here suggests a mechanism on the level of receptor recognition. The data were acquired through application of chemically synthesized lipopeptide fragments of the HBV L-protein that interact Tanespimycin solubility dmso with and inactivate an unknown HBV receptor. We provide evidence that the ability of HBV to address hepatocytes with high efficacy is triggered by the myristoylated N-terminal preS1-subdomain of L. The exclusive targeting of the respective

lipopeptides to the liver suggests that the HBV-receptor is liver-specific and not expressed in substantial amounts in other organs. The most remarkable finding of our study is the observation that wildtype HBVpreS1-lipopetides accumulate in livers of animals that are not susceptible for HBV. Using 26 peptides with different mutations, including exchanges of single L-amino acids with their respective D-enantiomers we demonstrated a tight correlation between the liver tropism in mice and the potency to inhibit HBV infection in vitro. Thus, receptor recognition of the HBVpreS-ligand is indistinguishable between mice and humans (and according DNA Damage inhibitor to the

data presented in Fig. 4A,B, also rats and dogs). The presence of an HBVpreS-receptor in rodents was unexpected and questions the hypothesis that the refractiveness of mice against HBV infection is caused by a deficiency in receptor-binding. However, the previous identification of Tupaia belangeri as a model for HBV infection30 implied that receptor expression is not limited to only closely related human species. The presence of an HBVpreS-specific receptor in mice and rats has important implications for the systematic development of immune competent small animal models for HBV and/or HDV. Since resistance learn more against infection cannot solely be explained by the lack of an HBV-specific binding receptor it is probably related to the lack of either a cofactor, involved in membrane fusion (which could even be functionally associated with the same molecule), or a factor controlling a subordinated step after the release of the nucleocapsid or both. Using the transplanted uPA-SCID mouse model Lutgehetmann et al.31 demonstrated that mouse hepatocytes are not susceptible to HDV infection in vivo. Given that mouse hepatocytes bind HDV we conclude that a factor/activity required for triggering membrane fusion is missing. The presence of an HBVpreS-specific receptor in mice should also be considered when using transplanted uPA/RAG2 mice as an in vivo infection model.32 These mice are susceptible to HBV and HDV.

The products of four genes (GPIBA, GPIBB, GP9 and GP5) assemble within maturing MK in the marrow to form the GPIb-IX-V complex. Mutations within GPIBA, GPIBB and GP9 in BSS prevent formation or trafficking of the complex through endoplasmic reticulum (ER) and the Golgi apparatus [6]. In rare variant forms, platelets express nonfunctional GPIbα; in platelet-type von Willebrand Carfilzomib in vitro disease (VWD), specific GPIBA mutations lead to upregulated GPIbα function and a clinical condition resembling type 2B VWD where macrothrombocytopenia (and sometimes circulating platelet aggregates) due to activating mutations in exon 28 of the VWF gene may also affect

megakaryopoiesis [7]. The platelet-collagen interaction under flow is a multistep process involving α2β1 and GPVI which signals through the FcRγ-chain [2,6]. Like α2β1, GPVI density is under Selleckchem Depsipeptide the control of SNPs and epigenetic factors; however, a loss in the collagen response due to mutations in GP6 occurs in rare families. Members of the seven transmembrane domain family of G-protein-linked receptors mediate platelet responses to soluble agonists. Rare patients with a decreased and reversible platelet aggregation to ADP have mutant alleles at the P2YR12 locus while a defective platelet aggregation to TXA2 is caused by mutations in TA2R. Significantly, these patients mimic the

platelet function modifications achieved in anti-thrombotic

therapy by clopidogrel (and prasugrel) and aspirin respectively. Decreased platelet aggregation to adrenaline is often seen in routine screening although its contribution to excessive bleeding is unclear. Abnormalities of signal transduction pathways into which surface receptors are locked mostly concern patients with mild bleeding while congenital deficiencies of metabolic pathways also lead to platelet function abnormalities [2,6,8–10]. IPDs of secretion (storage pool disease, SPD) cause selective defects learn more in aggregation. SPD affecting dense granules, storage sites for serotonin, ADP and ATP, may be quite common and the granule deficiency severe or partial. When associated with abnormalities of other lysosome-related organelles they give clearly defined phenotypes [e.g. Hermansky–Pudlak (HPS) and Chediak–Higashi (CHS) syndromes] where melanosomal defects cause a lack of pigmentation of the skin and hair. Defects in at least 8 genes (HPS-1 through HPS-8) in HPS cause distinct subtypes with the encoded proteins interacting in complexes (BLOCS); the genetic defects disrupt these thereby affecting organelle biosynthesis and protein trafficking. In CHS, bleeding is associated with severe immunologic defects and progressive neurological dysfunction, a lymphoproliferative syndrome and an accelerated phase is seen in ∼90% of patients.

(HEPATOLOGY 2010;52:1758-1768) Chronic cholestatic liver diseases such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are characterized by impaired biliary secretion of bile acids

and other potentially harmful cholephiles. Intrahepatic accumulation of endogenous hydrophobic bile acids, together with cytokine- and chemokine-mediated inflammatory bile ductular and liver parenchymal Enzalutamide concentration injury, may contribute to development of fibrosis and cirrhosis in chronic cholestatic disorders. The ratio of toxic to less toxic bile acids correlates with severity of liver injury.1 The hydrophilic C24 bile acid, ursodeoxycholic acid (UDCA) improves biochemical and histological features in PBC, halts progression to cirrhosis in the majority of patients with PBC, BMN 673 research buy normalizes life expectancy in two-thirds of patients with PBC2-5 and currently represents the only approved therapy for PBC.6 In PSC, its therapeutic long-term benefit remains so far unclear although serum liver tests and surrogate markers of long-term prognosis improved during UDCA treatment in pilot trials.6 Mechanisms of action of UDCA in cholestatic disorders have not yet been fully resolved.7 Stimulation of impaired hepatocellular secretion by mainly

posttranscriptional mechanisms, detoxification of bile, antiapoptotic effects in hepatocytes and cholangiocytes, and stimulation of cholangiocyte HCO secretion may contribute to the beneficial effect observed during UDCA treatment in cholestatic disorders.7 NorUDCA is a C23 homolog of UDCA. C23 bile acids are found only in trace amounts in human bile.8 They are poorly conjugated with taurine and glycine in liver, and their pharmacokinetic properties differ from their naturally occurring C24 homologs.8NorUDCA has recently been shown to exert therapeutic effects superior to those of UDCA in

multidrug resistance protein 2 (Mdr2)/ATP-binding cassette b4 (Abcb4) knockout mice, a murine model of nonsuppurative, sclerosing cholangitis.9, 10 The mechanisms of action of norUDCA selleck chemicals in Mdr2−/− mice remain obscure.10NorUDCA is a potent (hyper-)choleretic bile acid as a result of cholehepatic shunting.8, 10 Whether this property may explain, at least in part, the anticholestatic, anti-inflammatory, and antifibrotic effects of norUDCA in Mdr2−/− mice9, 10 still remains unresolved. Most importantly, it is unclear whether norUDCA, like UDCA, may exert anticholestatic effects at the level of the hepatocyte.7, 11 Lithocholic acid conjugates are the most potent cholestatic agents among the major human bile acids.12 Taurolithocholic acid (TLCA)-induced cholestasis is an established experimental model of hepatocellular cholestasis.

The rationale for adding metformin to rosiglitazone was to further improve the insulin Palbociclib supplier sensitivity and to mitigate the weight gain caused by rosiglitazone. However, presumably due to insufficient metformin dose, these benefits were not evident in this trial. There was no systematic monitoring of alcohol consumption, nutrient and calorie intake, or physical activity during the trial. Notwithstanding these limitations, we find this study to be appealing not only

because it represents the first serious attempt to use combination therapy to treat NASH but also is the first serious effort to investigate the role of losartan to improve fibrosis in NASH. What is next for the NASH treatment trials? Since there are no approved treatments for NASH, we believe that placebo-controlled trials are ethical and should be encouraged. It is possible that recent findings from the PIVENS and TONIC clinical trials may lead to extensive use of vitamin E by patients and practitioners, and in such a scenario the newer treatments would need to be tested against a vitamin E background. An important question selleck chemicals llc is if a combination of pioglitazone and vitamin E is more effective in treating NASH than these two agents given separately. There is an ongoing study of vitamin E and pioglitazone

combined in United States veterans and its results are awaited. There are two ongoing multicenter, phase IIb/III, placebo-controlled, randomized clinical trials in the United

States; one is comparing two different doses of ethyl icosapentate (EPA-E) to placebo, and the other trial is comparing obeticholic acid (FXR agonist) to placebo. It is possible that one or both may yield positive results, but it is unlikely that either compound will prove to be the magic bullet. We believe that combining agents that reduce hepatic influx/load of fatty acids (e.g., weight loss, insulin sensitizers) with agents that reduce lipotoxicity and cell injury (e.g., vitamin E, caspase inhibitors, pentoxifylline) is the best therapeutic strategy to investigate moving forward. Losartan and other proprietary antifibrotic compounds need to be tested, but more thought is needed with regard to the study population and the endpoints. Clinical trials with hard endpoints such as mortality, this website liver decompensation, and time to transplantation are difficult to conduct, and commonly used fibrosis endpoints are not sufficiently dynamic. One may have to consider alternative options such as elastography, enhanced liver fibrosis panel, or quantitative histological assessments that include markers of fibrogenesis and fibrosis. It is more logical to test antifibrotic compounds in combination with insulin sensitizers and/or antioxidants, rather than investigating them as sole agents. We encourage the academic and industry investigators to consider combination therapies and to incorporate recently published endpoints and clinical trial design for future clinical trials.

pylori multiple drug resistance (multidrug resistance, MDR). The purpose of this study is to study the role of efflux pump in clinical isolates of H. pylori, which resistant to dual or multiple antibiotics. Methods: Eight H. pylori clinical strains resistant to dual or multiple antibiotics were selected. We detected the expression of mRNA in three efflux pumps including hefA, hefB and hefC by Real-time Quantitative Polymerase chain Reaction (Real-time PCR). H.pylori strain 26695 was included as a control strain. Results: Compared

with the standard strains, there were two strains Decitabine price have different degrees of mRNA over-expression of hefC gene in the selected eight resistant strains. One strain had mRNA over-expression of hefB gene, two strains had over-expression of hefC and hefB. Over-expression of hefA was not found in any strain. Conclusions: There are difference in mRNA expression of efflux pump system in different H.pylori resistant strains. Further study about the role of efflux pump system in resistance of H.pylori R428 research buy are needed. Conclusion: There are difference in mRNA expression of efflux pump system in different H.pylori

resistant strains. Further study about the role of efflux pump system in resistance of H.pylori are needed. Key Word(s): 1. Helicobacter pylori; 2. antibiotic resistant; 3. efflux pump; 4. Real-time PCR; Presenting Author: ZHEN YANG Additional Authors: CHUAN XIE, GONGMEIZI LIU, XIMEI CAO, WEI LI, WENTING XU, NONGHUA LU Corresponding Author: NONGHUA LU Affiliations: The First Affiliated Hospital of Nanchang University Objective: Phosphorylation is the most important mechanism of post-translational modification of PTEN tumor suppressor, which results in loss of tumor suppressor function and increased cancer susceptibility. We investigated the role of PTEN phosphorylation in gastric cancer development in relation to learn more H. pylori infection. Methods: Gastric cancer tissues and cell lines, and tissue specimens of various stages of gastric carcinogenesis were used to

detect expression of PTEN and p-PTEN using Western blot or immunohistochemistry. Mongolian gerbils were challenged with H. pylori and their gastric tissues were used to detect expression of PTEN/PI3K/Akt signaling pathway related proteins using immunohistochemistry. Gastric epithelial cells were co-cultured with H. pylori and the regulation of PTEN/PI3K/Akt pathway was assessed by Western blot, flow cytometry, and MTT assay. Dominant-negative mutant or chemical inhibitors were used to inhibit activities of PTEN, PI3K, or Akt. Results: We found that in addition to previously reported reduced expression of PTEN, increased PTEN phosphorylation is also detected in gastric carcinogenesis, and more importantly, H. pylori is a trigger of PTEN phosphorylation, and induce PTEN phosphorylation started in chronic non-atrophic gastritis. H.

pylori multiple drug resistance (multidrug resistance, MDR). The purpose of this study is to study the role of efflux pump in clinical isolates of H. pylori, which resistant to dual or multiple antibiotics. Methods: Eight H. pylori clinical strains resistant to dual or multiple antibiotics were selected. We detected the expression of mRNA in three efflux pumps including hefA, hefB and hefC by Real-time Quantitative Polymerase chain Reaction (Real-time PCR). H.pylori strain 26695 was included as a control strain. Results: Compared

with the standard strains, there were two strains Daporinad price have different degrees of mRNA over-expression of hefC gene in the selected eight resistant strains. One strain had mRNA over-expression of hefB gene, two strains had over-expression of hefC and hefB. Over-expression of hefA was not found in any strain. Conclusions: There are difference in mRNA expression of efflux pump system in different H.pylori resistant strains. Further study about the role of efflux pump system in resistance of H.pylori PKC inhibitor are needed. Conclusion: There are difference in mRNA expression of efflux pump system in different H.pylori

resistant strains. Further study about the role of efflux pump system in resistance of H.pylori are needed. Key Word(s): 1. Helicobacter pylori; 2. antibiotic resistant; 3. efflux pump; 4. Real-time PCR; Presenting Author: ZHEN YANG Additional Authors: CHUAN XIE, GONGMEIZI LIU, XIMEI CAO, WEI LI, WENTING XU, NONGHUA LU Corresponding Author: NONGHUA LU Affiliations: The First Affiliated Hospital of Nanchang University Objective: Phosphorylation is the most important mechanism of post-translational modification of PTEN tumor suppressor, which results in loss of tumor suppressor function and increased cancer susceptibility. We investigated the role of PTEN phosphorylation in gastric cancer development in relation to selleck compound H. pylori infection. Methods: Gastric cancer tissues and cell lines, and tissue specimens of various stages of gastric carcinogenesis were used to

detect expression of PTEN and p-PTEN using Western blot or immunohistochemistry. Mongolian gerbils were challenged with H. pylori and their gastric tissues were used to detect expression of PTEN/PI3K/Akt signaling pathway related proteins using immunohistochemistry. Gastric epithelial cells were co-cultured with H. pylori and the regulation of PTEN/PI3K/Akt pathway was assessed by Western blot, flow cytometry, and MTT assay. Dominant-negative mutant or chemical inhibitors were used to inhibit activities of PTEN, PI3K, or Akt. Results: We found that in addition to previously reported reduced expression of PTEN, increased PTEN phosphorylation is also detected in gastric carcinogenesis, and more importantly, H. pylori is a trigger of PTEN phosphorylation, and induce PTEN phosphorylation started in chronic non-atrophic gastritis. H.

The animals were placed in a stereotactic frame and, with the head fixated, a midline scalp incision was made and two small boreholes were drilled in the skull. One borehole was used for the Veliparib placement of a catheter (PE-10) in the cisterna magna for ICP monitoring by connection to a pressure transducer. In the second borehole, we placed a laser Doppler probe (Probe 407; Perimed, Stockholm, Sweden) on the surface of the brain. The probe was connected to a Periflux Laser Doppler System 5000 monitor, allowing us to measure arbitrary values of blood velocity for later calculation of relative changes in CBF. Continuous measurements

of mean arterial pressure (MAP), ICP, and blood velocity were recorded on a computer using the software Perisoft (Perimed, Stockholm, Sweden). During the experiment, body temperature was monitored with an intraabdominal thermistor and maintained at 37°C with a heating blanket. Arterial blood

samples were taken regularly and pO2 and pCO2 analyzed (ABL 505; Radiometer, Copenhagen, Denmark). After an initialization period, stable baseline values were recorded, and intravenous ammonium acetate infusion 55 μmol/kg × min or saline infusion 2 mL/hour (0.9 mg/mL) was initiated (t = 0). Hypermagnesemia was induced in the appropriate groups by administration of MgSO4 as stated previously. The control groups in experiment B received an learn more equal volume of saline (vehicle) intraperitoneally Arterial blood samples Acalabrutinib were taken at t = 2 hours and t = 4 hours for measurement of total plasma magnesium (P-Mg), which were determined on a Roche Modular P analyzer with the use of colorimetry according to the manufacturer’s instructions. In addition, plasma levels of alanine aminotransferase, coagulation factors II+VII+X (PP), and ammonia

were determined at t = 4 hours. The experiment was ended after 4 hours, and the animals were sacrificed while anesthetized. After decapitation, cerebral cortex was removed from the brain and immediately frozen in liquid nitrogen and stored at −80°C for later analysis of glutamate, glutamine, and Aqp4 content. The cerebral cortical tissue was weighed and homogenized in a sixfold amount of ice-cold 1 mol/L HClO4. The homogenate was centrifuged and the supernatant neutralized by ice-cold 1.6 mol/L KOH containing 0.4 mol/L K2CO3. The concentrations of glutamate and glutamine were then measured in the supernatant by an enzymatic method using a YSI 2700 (YSI, Yellow Springs, OH), and the actual cortical concentration in the unit mmol/100 g could then be calculated. Frozen cortical brain tissue was homogenized in a Potter Elverhjem (B. Braun, Melsungen, Germany) at high speed for 4 minutes on ice in dissection buffer containing 0.32 M sucrose, 50 mM 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid buffer (pH 7.

The animals were placed in a stereotactic frame and, with the head fixated, a midline scalp incision was made and two small boreholes were drilled in the skull. One borehole was used for the selleck chemicals placement of a catheter (PE-10) in the cisterna magna for ICP monitoring by connection to a pressure transducer. In the second borehole, we placed a laser Doppler probe (Probe 407; Perimed, Stockholm, Sweden) on the surface of the brain. The probe was connected to a Periflux Laser Doppler System 5000 monitor, allowing us to measure arbitrary values of blood velocity for later calculation of relative changes in CBF. Continuous measurements

of mean arterial pressure (MAP), ICP, and blood velocity were recorded on a computer using the software Perisoft (Perimed, Stockholm, Sweden). During the experiment, body temperature was monitored with an intraabdominal thermistor and maintained at 37°C with a heating blanket. Arterial blood

samples were taken regularly and pO2 and pCO2 analyzed (ABL 505; Radiometer, Copenhagen, Denmark). After an initialization period, stable baseline values were recorded, and intravenous ammonium acetate infusion 55 μmol/kg × min or saline infusion 2 mL/hour (0.9 mg/mL) was initiated (t = 0). Hypermagnesemia was induced in the appropriate groups by administration of MgSO4 as stated previously. The control groups in experiment B received an selleck inhibitor equal volume of saline (vehicle) intraperitoneally Arterial blood samples check details were taken at t = 2 hours and t = 4 hours for measurement of total plasma magnesium (P-Mg), which were determined on a Roche Modular P analyzer with the use of colorimetry according to the manufacturer’s instructions. In addition, plasma levels of alanine aminotransferase, coagulation factors II+VII+X (PP), and ammonia

were determined at t = 4 hours. The experiment was ended after 4 hours, and the animals were sacrificed while anesthetized. After decapitation, cerebral cortex was removed from the brain and immediately frozen in liquid nitrogen and stored at −80°C for later analysis of glutamate, glutamine, and Aqp4 content. The cerebral cortical tissue was weighed and homogenized in a sixfold amount of ice-cold 1 mol/L HClO4. The homogenate was centrifuged and the supernatant neutralized by ice-cold 1.6 mol/L KOH containing 0.4 mol/L K2CO3. The concentrations of glutamate and glutamine were then measured in the supernatant by an enzymatic method using a YSI 2700 (YSI, Yellow Springs, OH), and the actual cortical concentration in the unit mmol/100 g could then be calculated. Frozen cortical brain tissue was homogenized in a Potter Elverhjem (B. Braun, Melsungen, Germany) at high speed for 4 minutes on ice in dissection buffer containing 0.32 M sucrose, 50 mM 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid buffer (pH 7.

In conclusion, we believe that previous studies proposing EMT as a significant source for collagen-producing myofibroblasts in the liver are limited by the approach, methodology, and quality of data. These studies rely on double-immunofluorescence staining of epithelial markers and surrogate markers for EMT but lack functional evidence for ECM production by hepatocytes-derived cells. Our study clearly identifies collagen-expressing cells, but none of which are derived from hepatocytes in vivo. Although we recognize the limitation of our study, our results strongly challenge

the concept that hepatocytes in vivo acquire a mesenchymal phenotype through EMT to produce ECM in liver Buparlisib nmr fibrosis. Additional Supporting Information may be found in the online version of this article. “
“Aim:  In spite of numerous studies on the association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC), the results are inconsistent and whether and how the effect of DM on the risk for HCC is PI3K Inhibitor Library modified or synergistically exerted by hepatitis virus infection are still unclear. We aimed to elucidate and quantify the effect modification and synergism between hepatitis B and C virus (HBV and HCV, respectively) and DM leading to the risk for HCC and also assess the independent contribution of DM to the risk for HCC at population level (population attributable fraction) in a high prevalence area of hepatitis virus infection. Methods:  A hospital-based

case–control study was conducted from one medical center. Information on hepatitis B and C virus infection and DM status

(defined by 8-h fasting blood glucose level ≥126 mg/dL, current use of oral hyperglycemic agent or insulin injection) was collected to assess interaction of hepatitis virus infection with DM on the risk for HCC. Results:  selleck chemical The association between DM and the risk for HCC was significant regardless of the presence of HBV infection, whereas a significant positive association was noted for HCV negativity. Synergistic interactions between DM and HBV infection were significant. In the absence of both hepatitis virus infections, the independent effect of DM accounted for 7.5% risk for HCC from the underlying population. Conclusion:  The effect of DM on the risk for developing HCC is higher in HCV negative patients and synergistic with HBV infection. The independent effect of DM provides a new insight to the prevention of HCC other than virus-related mechanism. “
“The impact of viral status on recurrence of hepatitis B-related hepatocellular carcinoma (HCC) after curative therapy remains controversial. This meta-analysis aimed to determine whether the presence of viral load, genotype, specific mutation and antiviral therapy influenced HCC recurrence after curative therapy. We performed a meta-analysis including 20 studies to assess the effect of viral status and antiviral therapy with nucleoside analog on recurrence of HCC after curative therapy.

The leak pressure of the suture closures (79 mm Hg) was comparatively higher than leak

pressures of clips (40 mm Hg) and OTSC (49.3 mm Hg) as previously reported using similar methods. Endolumenal suturing may offer the most robust method of reliable endoscopic full-thickness defect closure. Key Word(s): 1. Endoscopic closure; 2. endoscopic suturing; 3. perforation; 4. leak pressure Presenting Author: WILLIAM TAM Additional Authors: S YEAP Corresponding Author: WILLIAM TAM Affiliations: Lyell Mcewin Hospital Objective: Up to 5% of colonoscopies may be incomplete due to technical limitations such as bowel tortuosity or acute bowel angulation. Current options to visualise the remaining colon include CT/MRI colonography and enteroscope-assisted colonoscopy using either the push enteroscope or the single-balloon Selleck ITF2357 enteroscope. The former does not allow endoscopic intervention, while the latter technique is technically challenging. The study aims to evaluate the utility of cap and water-assisted colonoscopy www.selleckchem.com/products/FK-506-(Tacrolimus).html in patients with previous unsuccessful colonoscopy due to technical reasons. Methods: Patients with current indications for colonoscopy but who had a history of previous failed or incomplete colonoscopy underwent colonoscopy using combined cap application and water insufflation. Technical factors were deemed the major reasons for the incomplete colonoscopy

rather than inadequate bowel preparation or patient discomfort (all procedures had been performed using propofol sedation). In the current series, a transparent cap was attached to the tip of the scope for colonoscopy. Water insufflation was achieved using a foot-controlled water pump. Caecal intubation time (CIT) and total procedure time (TPT) were recorded using the Endobase software program. Results: Four consecutive patients underwent combined cap and water-assisted colonoscopy under propofol sedation by the same endoscopist check details (Table). Bowel preparation was satisfactory in all cases. The caecum was intubated in all cases, and polypectomy was successfully performed. There were no adverse events. Table: Results of patients who underwent cap and water-assisted

colonoscopy Age Sex Reason(s) for failed colonoscopy Previous unsuccessful attempts (No.) Pathology encountered Polypectomy (No.) CIT TPT 66M Acute angulation Colonoscopy (2) Diverticulosis Yes (1) <5 min 16 min 71F Bowel tortuosity Colonoscopy, Single balloon colonoscopy nil Yes (2) <10 min 23 min 79F Bowel tortuosity Colonoscopy nil Yes (1) <5 min 20 min 70M Bowel tortuosity, acute angulation Colonoscopy (3) Diverticulosis Yes (2) <10 min 33 min Conclusion: Performance of colonoscopy using both the distal cap attachment and water insufflation appeared to facilitate caecal intubation in patients in whom previous colonoscopies have been unsuccessful due to technical difficulties. Water insufflation in the left colon may straighten the left colon and shorten caecal intubation time.