Antioxidant, antibacterial, and anti-adhesive activities of biosurfactants isolated from Bacillus strains.

Biosurfactants are surface-active compounds that display a range of physiological functions. The present study investigated the antioxidant, antimicrobial, and anti-adhesive or anti-biofilm potential of biosurfactants isolated from Bacillus subtilis VSG4 and Bacillus licheniformis VS16. The antioxidant activity of the biosurfactants was studied in vitro using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals. At 5 mg/mL of the biosurfactant concentration, the scavenging of DPPH and hydroxyl radicals was found to be between 69.1-73.5% and 63.3-69.8%, respectively. The biosurfactants also displayed significant antibacterial activities against both Gram-positive and Gram-negative bacteria. The anti-adhesive activities of the biosurfactants were evaluated against Staphylococcus aureus ATCC 29523, Salmonella typhimurium ATCC 19430, and Bacillus cereus ATCC 11778. The biosurfactants exhibited anti-adhesive activity, even at concentrations of 3-5 mg/mL. Moreover, both biosurfactants displayed notable anti-biofilm activities with a biofilm eradication percentage ranging from 63.9 to 80.03% for VSG4 biosurfactant, and from 61.1-68.4% for VS16 biosurfactant. Furthermore, VSG4 biosurfactant exhibited emulsification and surface tension stability over a wide range of pH (4-10) and temperature up to 100 °C. These results show that VSG4 and VS16 biosurfactants can be potentially used as natural antioxidants, antimicrobials, and/or anti-adhesive agents for food and biomedical applications.

Clinical Relationship between Cholestatic Disease and Pituitary-Dependent Hyperadrenocorticism in Dogs: A Retrospective Case Series.

BACKGROUND: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). HYPOTHESIS/OBJECTIVES: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. ANIMALS: Sixty-five client-owned dogs with naturally occurring PDH. METHODS: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. RESULTS: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane.

4-n-butylresorcinol enhances proteolytic degradation of tyrosinase in B16F10 melanoma cells.

OBJECTIVE: 4-n-butylresorcinol is a competitive inhibitor of tyrosinase and has been used as an antimelanogenic agent. However, its inhibition mechanism in intact cells is not fully understood. To elucidate the cellular mechanism, we compared in vitro and in vivo inhibitory effects of 4-n-butylresorcinol on tyrosinase activity. METHODS: B16F10 melanoma cells were cultured in media containing α-MSH in the presence or absence of 4-n-butylresorcinol. Tyrosinase mRNA levels, protein levels and activity in B16F10 cells were compared by real-time PCR, immunostaining combined with western blot and colorimetric analysis, respectively. Melanin concentration was measured by colorimetry both in the cells and in the media. Tyrosinase glycosylation and proteolytic degradation were analysed by immunoblotting after cells were treated with Endo H/PNGase F and E64/proteasome inhibitors, respectively. RESULTS: 4-n-butylresorcinol inhibited tyrosinase activity and melanin synthesis more effectively in intact cells than in cell lysates. Western blotting and real-time RT-PCR showed that 4-n-butylresorcinol reduced protein levels, but not mRNA levels, of tyrosinase in B16F10 cells. 4-n-butylresorcinol showed no effect on the processing of tyrosinase glycosylation or on trafficking to melanosomes. However, treatment of B16F10 cells with E64 or proteasome inhibitor abrogated the 4-n-butylresorcinol-induced decrease of tyrosinase. Moreover, 4-n-butylresorcinol activated p38 MAPK, resulting in increased ubiquitination of tyrosinase. CONCLUSION: 4-n-butylresorcinol inhibits melanogenesis by enhancing proteolytic degradation of tyrosinase as well as competitive binding to tyrosinase. These findings will help to develop new, effective and safe chemicals for the treatment of hyperpigmentation disorders.

Long-term outcomes of locally or radically resected T1 colorectal cancer.

AIM: Little is known about the long-term outcome of T1 colorectal cancer (CRC) following curative resection. The present study addressed the long-term outcome of locally or radically resected T1 CRCs. METHOD: A total of 430 patients with T1 CRC who underwent local or radical resection were considered. Unfavourable histological factors were defined as positive resection margin, deep submucosal invasion, vascular invasion, Grade 3 and budding. The patients were classified as low-risk (unfavourable histological factor negative, n = 65) or high-risk (unfavourable histological factor positive, n = 365). RESULTS: Over a median follow-up of 78.4 months, disease recurred in 16 (3.7%) patients in the high-risk group, and no recurrence in the low-risk group. Resection type and vascular invasion were significantly associated with recurrence. In the vascular invasion (+) high-risk group, both 5-year disease-free survival rate and 5-year overall survival rate were significantly associated with resection type (radical 94.6%, local 43.8%, P < 0.001, and radical 99.1%, local 66.7%, P < 0.001). In the vascular invasion (-) high-risk group, 5-year disease-free survival rate was also significantly associated with resection type (radical 98.9%, local 84.7%, P = 0.001). However, 5-year overall survival rate was not associated with resection type (radical 98.9%, local 95.2%, P = 0.816). CONCLUSION: Local resection may be effective and oncologically safe in low-risk T1 CRC. Although additional surgery should be recommended for the locally resected high-risk T1 CRC cases, intensive surveillance without additional surgery and timely salvage operation may offer another treatment option, if vascular invasion is negative.

Effect of diallyl disulfide on acute gastric mucosal damage induced by alcohol in rats.

This study investigated the gastroprotective effects of diallyl disulfide (DADS), a secondary organosulfur compound derived from garlic (Allium sativum L.) on experimental model of ethanol (EtOH)-induced gastric ulcer in rats. The antiulcerogenic activity of DADS was evaluated by gross/histopathological inspection, pro-inflammatory cytokines, and lipid peroxidation with antioxidant enzyme activities in the stomach. DADS (100 mg/kg) was administered by oral gavage 2 h prior to EtOH treatment (5 ml/kg). The animals were killed 1 h after receiving EtOH treatment. Pretreatment with DADS attenuated EtOH-induced gastric mucosal injury, as evidenced by decreased severity of hemorrhagic lesions and gastric ulcer index upon visual inspection. DADS also prevented histopathological alterations and gastric apoptotic changes caused by EtOH. An increase in tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase was observed in the gastric tissues of EtOH-treated rats that coincided with increased serum TNF-α and interleukin 6 levels. In contrast, DADS effectively suppressed production of pro-inflammatory mediators induced by EtOH. Furthermore, DADS prevented the formation of gastric malondialdehyde and the depletion of reduced glutathione content and restored antioxidant enzyme activities, such as catalase, glutathione peroxidase, and glutathione reductase in the gastric tissues of EtOH-treated rats. These results indicate that DADS prevents gastric mucosal damage induced by acute EtOH administration in rats and that the protective effects of DADS may be due to its potent antioxidant and anti-inflammatory activities.

The early protective effect of glutamine pretreatment and ischemia preconditioning in renal ischemia-reperfusion injury of rat.

BACKGROUND: Heat shock proteins (HSP) play an important role in protecting cells against stress. METHODS: Using a rat model, we tested the hypothesis that pretreatment with glutamine (Gln) and ischemia preconditioning (IPC) increase the expression of HSP resulting in attenuation of renal ischemia/reperfusion (I/R) injury. Sprague-Dawley rats were randomized into 4 groups [group I, Gln injection (+), IPC (+); group II, Gln injection (+), IPC (-); group III, saline injection (+), IPC (+); group IV, saline injection (+), IPC (-)]. Renal HSP70 expression was determined by Western blotting and kidney function was assessed by blood urea nitrogen and serum creatinine. Renal cross-sections were microscopically examined for tubular necrosis, exfoliation of tubular epithelial cells, cast formation, and monocyte infiltration. RESULTS: Gln pretreatment increased intrarenal HSP expression (P = .031). In group I, tubulointerstitial abnormalities were clearly slighter compared with the other groups (P < .001). CONCLUSION: Our experiments suggest that (1) a single dose of Gln could induce HSP expression and (2) IPC could relieve renal I/R injury. In addition, IPC combined with Gln pretreatment had a synergic protective effect against renal I/R injury.

Validation of a scoring tool to predict drug-resistant pathogens in hospitalised pneumonia patients.

BACKGROUND: Health care-associated pneumonia (HCAP) affects a heterogeneous group of patients in frequent contact with health care systems. However, HCAP criteria poorly predict infection with drug-resistant (DR) pathogens. OBJECTIVE: To validate our previously reported risk-scoring model (predictive of DR pathogen infection) in patients admitted to hospital with pneumonia. DESIGN: We evaluated 580 patients admitted with culture-positive bacterial pneumonia. We identified risk factors, evaluated the risk-scoring model's capacity to predict infection by DR pathogens and compared the model's diagnostic accuracy with that of current HCAP criteria. RESULTS: DR pathogens were observed in 227/580 patients (39.1%). Of 269 HCAP patients, 153 (56.9%) were infected with DR pathogens. Overtreatment was more common in HCAP than in community-acquired pneumonia (58.7% vs. 41.2%, P < 0.001). Recent hospitalisation, admission from a long-term care facility, recent antibiotic treatment and tube feeding were independently associated with DR pathogens. For pathogen prediction, the risk-scoring model showed better diagnostic accuracy than HCAP criteria (area under receiver operating-characteristic curve = 0.723 vs. 0.673, P < 0.001). CONCLUSION: According to current HCAP criteria, half of the HCAP patients were treated unnecessarily with broad-spectrum antibiotics. Risk scoring by stratifying risk factors could improve the identification of patients likely to be infected with DR pathogens.

Effect of Lactobacillus plantarum CJLP243 on the growth performance and cytokine response of weaning pigs challenged with enterotoxigenic Escherichia coli.

The purpose of the present study was to evaluate the effect of diets containing Lactobacillus plantarum CJLP243 on the growth and cytokine response of weaning pigs (Sus scrofa) challenged with enterotoxigenic Escherichia coli (ETEC). In a 28-d experiment (14 d before and 14 d after challenge), a total of 108 pigs at 20 ± 1 d of age were allotted to 1 of 6 diets. These were a control diet without ETEC challenge (CON) and 5 treatment diets with ETEC challenge, including a control diet with ETEC challenge (negative control, NC); a positive control diet containing antibiotics (PC); control diet plus (10(8), 10(9), or 10(10)) cfu/kg L. plantarum CJLP243 (T1, T2, and T3, respectively). After challenge, NC showed the least ADFI, whereas PC and T3 had the greatest ADFI (P = 0.002). The ADG of PC, T2, and T3 were greater (P = 0.001) than that of CON, NC, and T1 during wk 1 to wk 2. During wk 3 to wk 4, a marked decline was seen in NC (P = 0.001) compared with CON, whereas PC and T3 showed increased ADG (P = 0.001). The overall ADG of PC and T3 were greater (P < 0.001) than the remaining groups. The PC and T3 had the greatest G:F during the second 2 wk (P = 0.002), and the overall 4-wk experimental period (P = 0.003). At 3 h after challenge, all groups except CON had greater rectal temperatures (RT; P < 0.05). The RT decreased to prechallenge temperatures at 9 h (PC and T3), 24 h (T1 and T2), and remained increased until d 7 in NC. At 7 and 14 d postinfection, the number of animals detected positive for ETEC by PCR assay was the greatest in NC; however, the PC group had the fewest ETEC-positive animals (P < 0.05), which was similar to T3. All challenged pigs, except T2, had greater concentrations of serum haptoglobin compared with CON, with the greatest concentration observed in NC (P < 0.001). Challenged pigs had increased serum concentrations of tumor necrosis factor alpha (TNF-α) 3 to 48 h postinfection, with the greatest concentration of TNF-α at 48 h observed in NC (P < 0.05). Similarly, greater (P < 0.05) serum concentrations of interferon-γ were observed for 9 h (T1 and T3), 24 h (T2 and PC), and 48 h (NC) postinfection. The serum concentration of IL-6 increased (P < 0.05) for 3 h in T3 and 24 h in NC. In conclusion, our findings suggest that L. plantarum CJLP243, at a concentration of 10(10) cfu/kg, may serve as a potential alternative to antibiotic supplementation to improve the growth and health performance of weaning pigs, especially during acute inflammation of the gut after bacterial infections.

Predictors for lymph node metastasis in T1 colorectal cancer.

BACKGROUND AND STUDY AIMS: It is critical that the risk of lymph node metastasis (LNM) is evaluated for determining the suitability of endoscopic resection for T1 colorectal cancer (CRC). Reported risk factors for LNM in completely resected T1 CRC are deep submucosal invasion, grade 3, angiolymphatic invasion, and budding. The aim of the present study was to identify the histopathologic factors associated with LNM in T1 CRC. PATIENTS AND METHODS: The study involved 435 patients with T1 CRC treated by endoscopic or surgical resection between January 2001 and April 2010 at the National Cancer Center, Korea. The 435 patients were classified into two groups - those undergoing surgical resection (n = 324) and those undergoing endoscopic resection (n = 111). In the surgically resected group, details regarding depth of submucosal invasion, angiolymphatic invasion, tumor grade, budding, and background adenoma (BGA) were evaluated with respect to presence or absence of LNM. In the endoscopically resected group, the results of follow-ups and additional salvage surgeries were studied. RESULTS: In the surgically resected group, LNM was detected in 42 patients (13.0 %). Grade 3, angiolymphatic invasion, budding, and the absence of BGA were identified as factors associated with LNM in univariate and multivariate analyses (P < 0.05). Among the 50 patients in the endoscopically resected group with high risk, three were diagnosed as being LNM-positive during the follow-up period. There was no LNM in the endoscopically resected group with low risk. CONCLUSIONS: Grade 3, angiolymphatic invasion, budding, and the absence of BGA are the risk factors that predict LNM in patients with T1 CRC. In cases where endoscopically resected T1 CRC has no risk factor, cautious follow-up could be recommended. However, if the tumor has any risk factor, additional surgical resection should be considered.

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection.

PURPOSE: To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT). METHODS: Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤ 0.15 [n=80], 0.16-0.3 [n=44], >0.3 [n=30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS). RESULTS: LNR (≤ 0.15, 0.16-0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p<0.001) and DFS (66.7%, 55.8%, and 21.9%; p<0.001) rates. In a multivariate analysis, LNR (≤ 0.15, 0.16-0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p<0.001) and DFS (HRs, 1, 1.699, and 3.960; p<0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥ 12 harvested LNs (p<0.05). CONCLUSION: LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.

[Docetaxel-based systemic chemotherapy in elderly Korean men with castration-resistant prostate cancer]. / Quimioterapia sistémica basada en docetaxel en hombres coreanos mayores con cáncer de próstata resistente a la castración.

INTRODUCTION: The aim of this study was to determine the efficacy and safety of docetaxel-based systemic chemotherapy in elderly patients with castration-resistant prostate cancer (CRPC). MATERIAL AND METHODS: We retrospectively reviewed the clinical records of 36 patients with CRPC who were treated with docetaxel-based systemic chemotherapy at a single institution between May 2005 and April 2010. After screening, 30 patients met the eligibility criteria, and were included. Patients were placed into 2 groups: group 1 consisted of 9 patients aged <70 years, and group 2 consisted of 21 patients aged ≥70 years. The treatment consisted of prednisolone (5mg) twice daily and docetaxel (75 mg/m(2)) once every 3 weeks. RESULTS: The median age was 72 years, and the median performance status was 0. The median baseline prostate specific antigen (PSA) was 33.8 ng/mL. The mean number of docetaxel chemotherapy cycles was 5.8. The PSA response rate was 48.2%, and the measurable disease response rate was 15.0%, and these rates did not differ between the two groups. The median time to PSA progression and median overall survival were 6 and 9 months, respectively. Five patients experienced grade 3 or higher neutropenia. The drug-related toxicity was not different between the two groups. CONCLUSIONS: The response of elderly CRPC patients with good performance status to docetaxel-based systemic chemotherapy was similar to that of younger patients. Docetaxel-based systemic chemotherapy is generally tolerated in elderly patients with good performance status.

Melatonin attenuates doxorubicin-induced testicular toxicity in rats.

This study investigated the protective effects of melatonin (MLT) against doxorubicin (DXR)-induced testicular toxicity and oxidative stress in rats. DXR was given as a single intraperitoneal dose of 10 mg kg(-1) body weight to male rats at 1 h after MLT treatment on day 6 of the study. MLT at 15 mg kg(-1) body weight was administered daily by gavage for 5 days before DXR treatment followed by an additional dose for 5 days. Sperm analysis, histopathological examination and biochemical methods were used for this investigation. DXR caused a decrease in the weight of seminal vesicles, epididymal sperm count and motility and an increase in the incidence of histopathological changes of the testis. In addition, an increased malondialdehyde (MDA) concentration and decreased glutathione content, glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase activities were observed. On the contrary, MLT treatment significantly ameliorated DXR-induced testicular toxicity in rats. Moreover, MDA concentration and GR, GST and SOD activities were not affected when MLT was administered in conjunction with DXR. These results indicate that MLT had a protective effect against DXR-induced testicular toxicity and that the protective effects of MLT may be due to both the inhibition of lipid peroxidation and increased antioxidant activity.

[The relationship between intravesical prostatic protrusion and pressure flow study findings in patients with benign prostate obstruction/lower urinary tract symptoms]. / Relación entre la protrusión prostática intravesical y los hallazgos del estudio de presión-flujo en pacientes con obstrucción prostática benigna/síntomas del tracto urinario inferior.

OBJECTIVES: To evaluate relationship between intravesical prostatic protrusion (IPP) on transrectal ultrasonography (TRUS) and pressure-flow study (PFS) findings in patients with benign prostatic obstruction/lower urinary tract symptoms (BPO/LUTS). MATERIAL AND METHODS: Between March 2006 and August 2009, we reviewed medical records of 87 patients who were underwent TRUS and PFS for evaluation of their LUTS. The patients were classified by the IPP vertical degree: less than 5 mm (group A), 5-10 mm (group B), over than 10 mm (groupC). The extent of bladder outlet obstruction was calculated as the bladder outlet obstruction index (BOOI) by the PFS. The obstruction was defined as the BOOI over 40. RESULTS: Mean age was 71.1 years, and mean IPP vertical was 8.23 mm. The IPP vertical showed significant correlation with prostate volume (r=0.688, P<0.001) and transitional zone volume (TZV) (r=0.645, P<0.001), but there was no correlation between IPP and International Prostate Symptom Score, maximal flow rate, post-voided residual urine and BOOI. The IPP transverse was significantly correlated with BOOI (r=0.213, P=0.048). CONCLUSIONS: The IPP vertical showed significant correlation with prostate volume and transitional volume, but not with severity of symptom, quality of life, parameters of PFS. However, the IPP transverse on TRUS was correlated with BOOI.

Genomic sequence of infectious hypodermal and hematopoietic necrosis virus (IHHNV) KLV-2010-01 originating from the first Korean outbreak in cultured Litopenaeus vannamei.

Due to the need to track and monitor genetic diversity, the genome of the infectious hypodermal and hematopoietic necrosis virus (IHHNV) strain KLV-2010-01 in cultured Litopenaeus vannamei shrimp that originated from the first Korean outbreak in 2010 was sequenced and analyzed. The genome, with a length of 3914 nucleotides, was sequenced from the Korean IHHNV. The genome encoded three large and overlapping open reading frames: ORF1 (NS-1) of 2001 bp, ORF2 (NS-2) of 1092 bp and ORF3 (capsid protein) of 990 bp. The overall organization, size and predicted amino acid sequence of the three ORFs in Korean IHHNV were highly similar to those of members of the infectious IHHNV group, and the most closely related strains were IHHNVs described from Ecuador and Hawaii. Additionally, phylogenetic analysis showed that the Korean IHHNV was clustered with lineage III in the infectious IHHNV group and was most similar to IHHNV isolates from Ecuador, China and Taiwan.

Inflammatory responses to Mycoplasma hyopneumoniae in murine alveolar macrophage cell lines.

AIM: To investigate the mechanism by which Mycoplasma hyopneumoniae induces inflammatory responses in murine alveolar macrophage (MH-S) cells. METHODS: A pathogenic strain of M. hyopneumoniae cultured in modified Friis medium was used to investigate the inflammatory response in MH-S cell lines. The effect of stimulation by M. hyopneumoniae on the production of nitric oxide (NO) and cytokines in MH-S cells and inhibition of their production, using specific inhibitors of signalling pathways, was investigated using the Griess reaction and ELISA respectively. A Western blot assay was used to confirm activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Nuclear translocation of NF-κB was further confirmed using transient transfection and luciferase gene reporter assay. RESULTS: The results revealed dose-dependent production of NO in MH-S cells stimulated by M. hyopneumoniae. Increased concentrations of the cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-1ß and IL-6 were also observed (p<0.05). Using immunoblot analysis, involvement of three MAPK pathways, extracellular signal-regulated kinase I/II (ERK1/2), p38 and Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK) was confirmed. Specific inhibitors of signal pathways also demonstrated their effect on the NO and cytokine responses of MH-S cells. Degradation and phosphorylation of inhibitory kappa B (IκB)-alpha was observed, while the luciferase gene reporter assays revealed activation of NF-κB after stimulation by M. hyopneumoniae. Inhibition of NF-κB by pyrrolidine dithiocarbamate decreased M. hyopneumoniae-induced production of NO and IL-1ß (p<0.05), whereas no inhibitory effect was observed on concentrations of TNF-α, and IL-6. CONCLUSION: These findings indicate that M. hyopneumoniae induces NO and pro-inflammatory cytokines, and NF-κB and the three MAPK pathways are involved in the process.

Clinicopathological differences of laterally spreading tumors of the colorectum according to gross appearance.

BACKGROUND AND STUDY AIMS: Laterally spreading tumors (LST) are classified into two subtypes, with the nongranular type harboring a higher risk of (pre)malignant changes than the granular type. Further subdifferentiation into two subgroups each has been suggested, but the clinical significance of such a subdifferentiation has not previously been studied in detail in larger numbers. PATIENTS AND METHODS: Out of 6499 patients diagnosed with colorectal adenomas between January 2006 and November 2008, 153 patients (2.35 %) had 158 LSTs, 96 with a granular and 62 with a nongranular pattern. The former group was subdivided into homogeneous and nodular mixed, the latter group into flat elevated and pseudodepressed. Clinical and histopathological parameters were compared among the four subtypes. RESULTS: Parameters were variably distributed between the four groups, with nodular mixed tumors being larger than the other three types ( P < 0.0001). As in other studies, malignant transformation and premalignant lesion (HGIN/CIS) were more frequent in nodular mixed than in homogeneous tumors (45.0 % vs. 5.6 %, P < 0.001), and also more common in pseudodepressed than in flat elevated tumors (41.7 % vs. 13.2 %, P = 0.011). Submucosal invasive cancer was present in 8.3 % of nodular mixed tumors, 7.9 % of flat elevated, and 12.5 % of pseudodepressed, while it was absent in homogeneous tumors. Serrated adenoma was identified in 10.8 % of all LSTs, and sessile serrated adenoma tended to be more common in flat elevated tumors. CONCLUSIONS: Further subdifferentiation of the LST lesions to identify lesions at risk of malignant transformation makes most sense in the granular type. Among nongranular LSTs, both subtypes carry a significant risk.

Transglutaminase 2 suppresses apoptosis by modulating caspase 3 and NF-kappaB activity in hypoxic tumor cells.

The expression of hypoxia-inducible factor-1 (HIF-1) correlates with poor clinical outcomes and confers resistance to the apoptosis of the tumor cells that are exposed to hypoxia. Presently, the mechanism underlying this phenomenon is poorly understood. In this study we provide evidence that transglutaminase 2 (TG2), an enzyme that catalyses protein crosslinking reactions, is a transcriptional target of HIF-1 to enhance the survival of hypoxic cells. We found that hypoxia induces TG2 expression through an HIF-1 dependent pathway and concurrently activates intracellular TG2. The hypoxic cells overexpressing TG2 showed resistance to apoptosis. Conversely, the hypoxic cells treated with either TG2 inhibitor or small interfering RNA (siRNA) became sensitive to apoptosis. Activation of TG2 in response to hypoxic stress inhibited caspase-3 activity by forming crosslinked multimer, resulting in insoluble aggregates. TG2 also activates nuclear factor (NF)-kappaB pathway after hypoxic stress, and thereby induces the expression of cellular inhibitor of apoptosis 2. The anti-apoptotic role of TG2 was further confirmed in vivo using xenografts in athymic mice. Our results indicate that TG2 is an anti-apoptotic mediator of HIF-1 through modulating both apoptosis and survival pathways and may confer a selective growth advantage to tumor cells. These findings suggest that the inhibition of TG2 may offer a novel strategy for anticancer therapy.

Developmental toxic potential of 1,3-dichloro-2-propanol in Sprague-Dawley rats.

This study investigated the potential adverse effects of 1,3-dichloro-2-propanol (1,3-DCP) on pregnant dams and the embryo-fetal development after maternal exposure on gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 10, 30, and 90mg/kg per day (n=10 for each group). All dams underwent Caesarean sections on GD 20, and their fetuses were examined for morphological abnormalities. Maternal toxicity was noted at 90mg/kg/day. Manifestations of toxicity included clinical signs of illness, lower body weight gain, decreased food intake, and increases in the weight of the adrenal glands and the liver. Developmental toxic effects including decreases in fetal body weight and increases in visceral and skeletal variations also occurred at the highest dose. At 30mg/kg, only a minimal maternal toxicity, including a decrease in maternal food intake and an increase in the liver weight, was observed. No adverse maternal or developmental effects were observed at 10mg/kg/day. These results revealed that a 14-day repeated oral dose of 1,3-DCP was minimally embryotoxic but not teratogenic at a maternal toxic dose (90mg/kg/day), and was not embryotoxic at a minimally maternal toxic dose (30mg/kg/day) in rats. Because the developmental toxicity of 1,3-DCP was observed only in the presence of maternal toxicity, it is concluded that the developmental findings observed in the present study are secondary effects to maternal toxicity. Under these experimental conditions, the no-observed-adverse-effect level of 1,3-DCP is considered to be 10mg/kg/day for dams and 30mg/kg/day for embryo-fetal development.

Lupus-associated pancreatitis complicated by pancreatic pseudocyst and central nervous system vasculitis.

Pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE), but this can occasionally cause major complications. We report in this article, a case of 33-year-old female patient who developed lupus-associated pancreatitis that was subsequently complicated by pancreatic pseudocyst and central nervous system (CNS) vasculitis. Abdominal computed tomography (CT) showed an oedematous swelling of the pancreas and a pseudocyst measuring 4 x 3 cm2. Brain magnetic resonance imaging (MRI) showed multiple high-signal intensity lesions in both cerebral hemispheres. The pseudocyst did not completely resolve with high-dose steroid therapy, and it was later complicated by infection and rupture. After a surgical drainage for the complicated pseudocyst, her clinical symptoms and signs were markedly improved. This case shows the importance of performing early drainage rather than conservative treatment for a pancreatic pseudocyst in a patient with lupus-associated pancreatitis.