Foreign bodies in the rectum – an unusual surgical problem

A foreign body in the rectum is not a very common emergency case in surgical practice, of various etiology. In the years 2003-2011, 8 people were hospitalised in the Clinic of General and Colorectal Surgery due to a foreign body in the rectum. All the patients were male. All of them were qualified for foreign body removal in a surgical suite, under general anaesthesia due to a potential need for expanding the scope of the procedure. In all situations attempts were made at removing the object through the anus, which proved successful in 7 cases, without complications.In one case the scope of the procedure needed to be expanded with laparotomy and sigmoidotomy, through which the foreign body was removed. This procedure was also carried out with no complications

Antiproliferative Activity of Melanoidins Isolated from Heated Potato Fiber (Potex) in Glioma Cell Culture Model

Potex constitutes a potato fiber preparation widely used as an ingredient to meat and bakery products which thermal treatment results in creation of new compounds. Melanoidins are high molecular weight brown end products of Maillard reaction, and few data presenting tumor cell growth inhibiting activity of melanoidins have been reported. Thus, in present study we utilized water extract of Potex roasted (180 degrees C for 2 h), whose chemical characterization revealed the presence of melanoidin complexes. Heated Potex extract inhibited C6 glioma cell proliferation in a dose-dependent manner measured by MTT method. High molecular weight components present in initial extract were responsible for stronger antiproliferative effect compared with low molecular weight fraction. Impaired MAPK (mitogen-activated protein kinase) and Akt signaling was found in cells treated with the extract. Moreover, flow cytometry analyses revealed the extract to induce G(1)/S arrest in glioma cells. Simultaneously, Western blot analysis showed elevated levels of p21 protein with concomitant decrease of cyclin D1. In conclusion, observed antiproliferative activity of melanoidins present in heated Potex was linked to disregulated MAPK and Akt signaling pathways, as well as to cell cycle cessation. These results suggest potential application of Potex preparation as a functional food ingredient and chemopreventive agent

Melanoidins isolated from heated potato fiber (Potex) affect human colon cancer cells growth via modulation of cell cycle and proliferation regulatory proteins

Melanoidins are brown, nitrogen containing, high molecular weight end products of Maillard reaction with poorly established activity towards tumor cells. The goal of present study was to verify whether both heated potato fiber Potex extract (180 degrees C for 2 h) and melanoidins isolated from the extract exerts growth-inhibiting activity in human colon cancer cells in vitro. The cells of LS180 colon cancer cell line were tested upon treatment with roasted potato fiber extract (AM4) as well as with high (HMW) and low (LMW) molecular weight fractions isolated from the extract, since both may be regarded as/or contain melanoidins. The tested compounds at concentration of 1000 mu g/ml reduced cell growth down to 45%, 69% and 54%, respectively. Furthermore, deregulated ERK1/2 signaling was revealed upon treatment. Moreover, multiple alternations in cell cycle regulators activity were found (i.e. cyclinD1, cyclin-dependent kinase 4 and 6, p21, p27, p53, pRb) leading to cell cycle cessation in GO phase. Importantly, LMW compounds revealed markedly stronger potential to alter specific molecular targets comparing to HMW compounds. Summarizing, the results emphasize that both high and low molecular weight melanoidins contribute to antiproliferative activity of heated potato fiber in LS180 colon cancer cells in vitro. (C) 2013 Elsevier Ltd. All rights reserved

Alpha-ketoglutarate (AKG) inhibits proliferation of colon adenocarcinoma cells in normoxic conditions

Background and objective. Alpha-ketoglutarate (AKG), a key intermediate in Krebs cycle, is an important biological compound involved in the formation of amino acids, nitrogen transport, and oxidation reactions. AKG is already commercially available as a dietary supplement and its supplementation with glutamine, arginine, or ornithine alpha-ketoglutarate has been recently considered to improve anticancer immune functions. It is well documented that AKG treatment of Hep3B hepatoma cells in hypoxia induced HIF-alpha (hypoxia-inducible factor) degradation and reduced vascular endothelial growth factor (VEGF) synthesis. Moreover, AKG showed potent antitumor effects in murine tumor xenograft model, inhibiting tumor growth, angiogenesis, and VEGF gene expression. However, the mechanisms of its anticancer activity in normoxia have not been examined so far. Results. Here, we report that in normoxia, AKG inhibited proliferation of colon adenocarcinoma cell lines: Caco-2, HT-29, and LS-180, representing different stages of colon carcinogenesis. Furthermore, AKG influenced the cell cycle, enhancing the expression of the inhibitors of cyclin-dependent kinases p21 Waf1/Cip1 and p27 Kip1. Moreover, expression of cyclin D1, required in G1/S transmission, was decreased, which accompanied with the significant increase in cell number in G1 phase. AKG affected also one the key cell cycle regulator, Rb, and reduced its activation status. Conclusion. In this study for the first time, the antiproliferative activity of AKG on colon adenocarcinoma Caco-2, HT-29, and LS-180 cells in normoxic conditions was revealed. Taking into consideration an anticancer activity both in hypoxic and normoxic conditions, AKG may be considered as a new potent chemopreventive agent

Expression of matricellular proteins in human uterine leiomyomas and normal myometrium

Growth of human leiomyomas can probably be initiated as a response to injury, in a way similar to the development of keloids. Among many bioactive molecules, which are implicated in tissue repair, a pivotal role is attributed to matricellular proteins. The aim of the current study was to evaluate the immunohistochemical expression of tenascin-C (TNC), thrombospondin-1 (TSP-1), SPARC/osteonectin and tenascin-X (TNX) in human uterine leiomyomas and normal myometrium. Immunostaining was performed on 33 pairs of paraffin-fixed sections and 9 cell-lines derived from uterine leiomyomas and normal myometrium. Fifteen (45.5%) leiomyomas investigated were positive for TNC, whereas all normal myometrial samples were immunonegative (χ2=19.41; p<0.001). Immunostaining for TSP-1 was observed in 20 (60.6%) uterine fibroids and in 12 (36.4%) control samples (χ2=3.88; p<0.05). The expression of SPARC/osteonectin protein was more frequently found in leiomyomas than in normal myometrium, but this difference was not significant. Apart from one fibroid culture and one myometrial culture, all the others revealed strong TNC immunostaining. Expression of TSP-1 and SPARC/osteonectin was weak to moderate in all established cell-lines. None of the tissues or cell lines investigated showed positive staining for TNX. In conclusion, TSP-1 and TNC are likely to play important roles in the pathogenesis of uterine leiomyomas, presumably affecting cell proliferation and/or extracellular matrix deposition

Antiglioma Potential of Coumarins Combined with Sorafenib

Coumarins, which occur naturally in the plant kingdom, are diverse class of secondary metabolites. With their antiproliferative, chemopreventive and antiangiogenetic properties, they can be used in the treatment of cancer. Their therapeutic potential depends on the type and location of the attachment of substituents to the ring. Therefore, the aim of our study was to investigate the effect of simple coumarins (osthole, umbelliferone, esculin, and 4-hydroxycoumarin) combined with sorafenib (specific inhibitor of Raf (Rapidly Accelerated Fibrosarcoma) kinase) in programmed death induction in human glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cells lines. Osthole and umbelliferone were isolated from fruits: Mutellina purpurea L. and Heracleum leskowii L., respectively, while esculin and 4-hydroxycoumarin were purchased from Sigma Aldrich (St. Louis, MO, USA). Apoptosis, autophagy and necrosis were identified microscopically after straining with specific fluorochromes. The level of caspase 3, Beclin 1, PI3K (Phosphoinositide 3-kinase), and Raf kinases were estimated by immunoblotting. Transfection with specific siRNA (small interfering RNA) was used to block Bcl-2 (B-cell lymphoma 2), Raf, and PI3K expression. Cell migration was tested with the wound healing assay. The present study has shown that all the coumarins eliminated the MOGGCCM and T98G tumor cells mainly via apoptosis and, to a lesser extent, via autophagy. Osthole, which has an isoprenyl moiety, was shown to be the most effective compound. Sorafenib did not change the proapoptotic activity of this coumarin; however, it reduced the level of autophagy. At the molecular level, the induction of apoptosis was associated with a decrease in the expression of PI3K and Raf kinases, whereas an increase in the level of Beclin 1 was observed in the case of autophagy. Inhibition of the expression of this protein by specific siRNA eliminated autophagy. Moreover, the blocking of the expression of Bcl-2 and PI3K significantly increased the level of apoptosis. Osthole and sorafenib successfully inhibited the migration of the MOGGCCM and T98G cells

Pacjenci z nasilonymi zwapnieniami w naczyniu odpowiedzialnym za niedokrwienie, poddawani zabiegom angioplastyki wieńcowej z powodu zawału serca cechują się złym rokowaniem w obserwacji odległej

Background: To assess the influence of severe target lesion calcification (TLC) on the outcomes of patients undergoing percutaneous coronary interventions (PCI) due to acute myocardial infarction (AMI). Aim: Contemporary data concerning coronary artery calcifications (CAC) are based on pooled analyses from randomised trials with short follow-up. We still lack the knowledge on how CAC in target lesions affect long-term prognosis of patients with AMI in everyday practice. Methods: We evaluated clinical and laboratory data of 206 consecutive patients who underwent coronary angiography and PCI due to AMI. Primary endpoints were all-cause death and recurrent hospitalisations due to acute coronary syndrome (ACS). Results: Severe TLC lesions were present in 17% of patients. These patients were older (71 vs. 65 years, p = 0.02) and more often diagnosed with non-ST segment elevation myocardial infarction (77% vs. 58%, p = 0.03). Patients with severe TLC had lower rates of PCI success (80% vs. 97%, p &lt; 0.0001) and less often achieved full revascularisation during index procedure (14% vs. 41%, p = 0.003). During 30 months follow-up patients with severe TLC more often suffered from another ACS (37% vs. 13%, p = 0.0005) and had higher all-cause mortality (31% vs. 16%, p = 0.04). Multivariate Cox regression model showed severe TLC to be an independent predictor of another ACS (HR 2.8; 95% CI 1.4–5.6; p = 0.004). Conclusions: Severe TLC are not uncommon in patients with ACS. The presence of severe TLC is a prognostic factor of another ACS in AMI patients undergoing PCI.Wstęp: Aktualne dane dotyczące wyników leczenia przezskórnego pacjentów z nasilonymi zwapnieniami w tętnicach wieńcowych pochodzą z badań klinicznych o krótkim okresie obserwacji. Nadal brakuje aktualnych informacji na temat odległych wyników zabiegów angioplastyki u chorych z zawałem serca i nasilonymi zwapnieniami w naczyniu odpowiedzialnym za niedokrwienie. Cel: Celem pracy była ocena częstości występowania i wpływu na odległe wyniki leczenia przezskórnego nasilonych zwapnień w naczyniu odpowiedzialnym za niedokrwienie u pacjentów hospitalizowanych z powodu zawału serca. Metody: Oceniono dane kliniczne i zabiegowe 206 kolejnych pacjentów poddanych zabiegom angioplastyki wieńcowej z powodu zawału serca. Pierwszorzędowymi punktami końcowymi były zgon z dowolnej przyczyny i kolejna hospitalizacja z powodu ostrego zespołu wieńcowego. Wyniki: Nasilone zwapnienia w naczyniu odpowiedzialnym za niedokrwienie były obecne u 17% chorych. Pacjenci ci byli starsi (71 vs. 65 lat; p = 0,02) i częściej hospitalizowani z rozpoznaniem zawału serca bez uniesienia odcinka ST. Skuteczność zabiegów angioplastyki wieńcowej (80% vs. 97%; p &lt; 0,0001) oraz odsetek pełnej rewaskularyzacji podczas pierwszego zabiegu (14% vs. 41%; p = 0,003) były również niższe w tej grupie chorych. Podczas 30-miesięcznej obserwacji osoby z nasilonymi zwapnieniami w naczyniu odpowiedzialnym za niedokrwienie częściej doznawali kolejnego ostrego zespołu wieńcowego (37% vs. 13%; p = 0,0005) oraz charakteryzowali się wyższą śmiertelnością całkowitą (31% vs. 16%; p = 0,04). Wieloczynnikowy model regresji Coxa wskazał nasilone zwapnienia w naczyniu odpowiedzialnym za niedokrwienie jako niezależny predyktor kolejnej hospitalizacji z powodu ostrego zespołu wieńcowego (HR 2,8; 95% CI 1,4–5,6; p = 0,004). Wnioski: Nasilone zwapnienia w naczyniu odpowiedzialnym za niedokrwienie nie są rzadkim zjawiskiem u chorych hospitalizowanych z powodu zawału serca. Ich obecność jest czynnikiem predykcyjnym wystąpienia kolejnego ostrego zespołu wieńcowego w tej populacji pacjentów

Photoactive Liposomal Formulation of PVP-Conjugated Chlorin e6 for Photodynamic Reduction of Atherosclerotic Plaque

Background: Liposomes serve as delivery systems for biologically active compounds. Existing technologies inefficiently encapsulate large hydrophilic macromolecules, such as PVP-conjugated chlorin e6 (Photolon). This photoactive drug has been widely tested for therapeutic applications, including photodynamic reduction of atherosclerotic plaque. Methods: A novel formulation of Photolon was produced using &ldquo;gel hydration technology&rdquo;. Its pharmacokinetics was tested in Sus scrofa f. domestica. Its cellular uptake, cytotoxicity, and ability to induce a phototoxic reaction were demonstrated in J774A.1, RAW264.7 macrophages, and vascular smooth muscle (T/G HA-VSMC) as well as in vascular endothelial (HUVEC) cells. Results: Developed liposomes had an average diameter of 124.7 &plusmn; 0.6 nm (polydispersity index (PDI) = 0.055) and contained &gt;80% of Photolon). The half-life of formulation in S. scrofa was 20 min with area under the curve (AUC) equal to 14.7. The formulation was noncytotoxic in vitro and was rapidly (10 min) and efficiently accumulated by macrophages, but not T/G HA-VSMC or HUVEC. The accumulated quantity of photosensitizer was sufficient for induction of phototoxicity in J774A.1, but not in T/G HA-VSMC. Conclusions: Due to the excellent physical and pharmacokinetic properties and selectivity for macrophages, the novel liposomal formulation of Photolon is a promising therapeutic candidate for use in arteriosclerosis treatment when targeting macrophages but not accompanying vascular tissue is critical for effective and safe therapy