A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Pneumonia‐induced sepsis in mice: temporal study of inflammatory and cardiovascular parameters

The aim of the present work is to provide a better comprehension of the pneumonia‐induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF‐α and IL‐1β levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS‐2 expression appeared late after bacteria inoculation, whereas levels of NOS‐1 and NOS‐3 were unchanged. The high NOS‐2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae‐induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.     

Multivariate analysis of the influence of peri-implant clinical parameters and local factors on radiographic bone loss in the posterior maxilla: a retrospective study on 277 dental implants

Clinical Oral Investigations - The aim of the present study was to investigate whether peri-implant clinical parameters (modified plaque index (mPI), bleeding and/or suppuration on probing (B/SOP))...     

Histological and mucin histochemical study of the small intestine of the Persian squirrel (Sciurus anomalus)

This article describes the histological and mucin histochemical properties of the small intestine of the Persian squirrel (Sciurus anomalus). This species is widely distributed in the Middle East and can be found as a companion animal. The histological studies revealed that the plicae circulares were not visible in the tunica mucosa. The maximum height and width of the villi were observed in the duodenum, which then decreased toward the ileum. The muscularis mucosa was scattered, whereas the tunica submucosa was composed of dense connective tissue. The lymphatic nodules were seen in the submucosa of the distal part of the jejunum and ileum, and Brunner’s glands were embedded in the initial portion of the duodenum. The tunica muscularis was significantly thicker in the ileum, and the circular muscle layer was thicker than the longitudinal muscle layer throughout the entire length of the small intestine. The mucin histochemistry, which was examined using the periodic acid-Schiff (PAS) and alcian blue (AB) (pH 1.0 and 2.5) and also PAS–AB (pH 2.5) and aldehyde fuchsin-AB (pH 2.5) techniques coupled with methylation and saponification reaction for some sections, showed that the small intestine mucous content included both carboxylated and sulfated acidic mucins with few neutral mucins. The results of this study contribute to the knowledge of the histological and histochemical characteristics of the gastrointestinal tracts of exotic mammals and provide data for comparison with other mammals.     

No evidence of enteroviruses in the intestine of patients with type 1 diabetes

Aims/hypothesis  

The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes.     

Experimental periodontitis promotes transient vascular inflammation and endothelial dysfunction

Objectives

This study aimed to evaluate the systemic inflammatory response and cardiovascular changes induced by experimental periodontitis in rats.

Design

Experimental periodontitis was induced by placing a cotton ligature around the cervix of both sides of mandibular first molars and maxillary second molars in each male rat. Sham-operated rats had the ligature removed immediately after the procedure. Seven, 14 or 28 days after procedure, the effects of acetylcholine, sodium nitroprusside and phenylephrine were evaluated on blood pressure, aortic rings and isolated and perfused mesenteric bed. The blood was obtained for plasma Interleukin-6 (IL-6), C-reactive protein (CRP) and lipid evaluation. The mesenteric vessels were obtained to evaluate superoxide production and nitric oxide synthase 3 (NOS-3) expression.

Results

Ligature induced periodontitis reduced endothelium-dependent vasodilatation, a hallmark of endothelial dysfunction. This effect was associated with an increase in systemic inflammatory markers (IL-6 and CRP), worsens on lipid profile, increased vascular superoxide production and reduced NOS-3 expression. It is interesting to note that many of these effects were transitory.

Conclusion

Periodontitis induced a transient systemic and vascular inflammation which leads to endothelial dysfunction, an initial step for cardiovascular diseases. Moreover, the animal model of periodontitis used here may represent a valuable tool for studying the relationship between periodontitis and endothelial dysfunction.