Influence of flow design on microcirculation in conditions of undulation pump-left ventricle assist device testing

To study the microvessels in bulbar conjunctiva, we conducted an experiment in goat with a pneumatically driven left heart bypass pump, which was replaced with an undulation pump-left ventricle assist device for 9 days. Three flow patterns were tested: complete pulsatile, continuous, and percentage of pulsatile. We studied the morphology of arterioles and venules of the bulbar conjunctiva using photograph records. The setting up of continuous flow caused global vasoconstriction (significant in venules-P < 0.05). During the pumping in the pulsatile and percentage of pulsatile modes, no significant changes of microvessel morphology were observed. The findings described could point to some disturbances in the microcirculatory bed in conditions of continuous flow.     

Primary bilateral angiosarcoma of the breast treated with neoadjuvant chemotherapy combined with propranolol

A case report of bilateral primary angiosarcoma treated with neoadjuvant chemotherapy was presented. A routine diagnostic mammography and ultrasound examinations indicated abnormalities in both breasts of the patient, confirmed on MRI as large bilateral masses. Core needle biopsy revealed angiosarcoma G1. The treatment agreed during the interdisciplinary meeting involved chemotherapy combined with simultaneous blockade of beta-adrenergic receptors, followed by bilateral simple mastectomy. This case highlights the importance of a patient-focused care.     

Hepatocyte expression of TRAIL pathway regulators correlates with histopathological and clinical parameters in chronic HCV infection

Background and aims

Treatment with pegylated interferon-alpha (PEG-IFN) and ribavirin is the backbone of standard therapy of HCV by mechanisms that are not completely understood. Besides a direct antiviral effect, different immunomodulatory and apoptotic effects have been discussed. Tumor necrosis factor-related apoptosis inducing-ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family with immunomodulatory as well as pro- and antiapoptotic effects and is putatively involved in control of HCV infection. Thus, we analyzed the expression of the TRAIL/TRAIL-receptor system, caspase-8 and cFLIP and examined their prognostic and predictive value for HCV infection and antiviral therapy, respectively.

Methods

We immunohistochemically analyzed liver biopsies of 116 therapy-naive HCV patients before treatment with PEG-IFNα and ribavirin in comparison to healthy liver tissue. Expression levels of TRAIL, TRAIL-R1 to TRAIL-R4, caspase-8 and cFLIP were correlated with sustained virologic response (SVR), genotype and staging of chronic hepatitis.

Results

Caspase-8, cFLIP, TRAIL-R2 and TRAIL-R4 were strongly upregulated in HCV patients, whereas TRAIL-R3 was downregulated. SVR correlated with high expression of TRAIL and pro-apoptotic TRAIL-R2 on HCV infected hepatocytes.

Conclusions

Our results suggest a pathophysiological role of TRAIL in both, HCV infection and therapy. Further studies need to elaborate possible TRAIL-related targets for clinical applications.     

Ultrasound appearances after mesh implantation��evidence of mesh contraction or folding?

Introduction and hypothesis  

Polypropylene meshes are frequently used in abdominal and vaginal reconstructive surgery. Recently, several authors have claimed that mesh-associated complications may be linked to mesh shrinkage. We have performed a prospective study with postoperative follow-up by ultrasound examination at two time points after Prolift anterior implantation to assess changes in the ultrasound appearance of mesh implants over time.     

Phosphorylation of carbonic anhydrase IX controls its ability to mediate extracellular acidification in hypoxic tumors

In the hypoxic regions of a tumor, carbonic anhydrase IX (CA IX) is an important transmembrane component of the pH regulatory machinery that participates in bicarbonate transport. Because tumor pH has implications for growth, invasion, and therapy, determining the basis for the contributions of CA IX to the hypoxic tumor microenvironment could lead to new fundamental and practical insights. Here, we report that Thr443 phosphorylation at the intracellular domain of CA IX by protein kinase A (PKA) is critical for its activation in hypoxic cells, with the fullest activity of CA IX also requiring dephosphorylation of Ser448. PKA is activated by cAMP, which is elevated by hypoxia, and we found that attenuating PKA in cells disrupted CA IX-mediated extracellular acidification. Moreover, following hypoxia induction, CA IX colocalized with the sodium-bicarbonate cotransporter and other PKA substrates in the leading edge membranes of migrating tumor cells, in support of the concept that bicarbonate metabolism is spatially regulated at cell surface sites with high local ion transport and pH control. Using chimeric CA IX proteins containing heterologous catalytic domains derived from related CA enzymes, we showed that CA IX activity was modulated chiefly by the intracellular domain where Thr443 is located. Our findings indicate that CA IX is a pivotal mediator of the hypoxia-cAMP-PKA axis, which regulates pH in the hypoxic tumor microenvironment.