Cancer-retina antigens as potential paraneoplastic antigens in melanoma-associated retinopathy

Melanoma-associated retinopathy is a rare paraneoplastic neurological syndrome characterized by retinopathy in melanoma patients. The main photoreceptor proteins have been found to be expressed as cancer-retina antigens in melanoma. Here we present evidence that these can function as paraneoplastic antigens in melanoma-associated retinopathy. Sera and one tumor cell line of such patients were studied and ret-transgenic mice spontaneously developing melanoma were used as a murine model for melanoma-associated retinopathy. Splenocytes and sera were used for adoptive transfer from tumor-bearing or control mice to wild-type mice. Retinopathy was investigated in mice by funduscopy, electroretinography and eye histology. Expression of photoreceptor proteins and autoantibodies against arrestin and transducin were detected in melanoma-associated retinopathy patients. In tumor-bearing ret-transgenic mice, retinopathy was frequently (13/15) detected by electroretinogram and eye histology. These pathological changes were manifested in degenerations of photoreceptors, bipolar cells and pigment epithelium as well as retinal detachment. Mostly these defects were combined. Cancer-retina antigens were expressed in tumors of these mice, and autoantibodies against arrestin were revealed in some of their sera. Adoptive transfer of splenocytes and sera from tumor-bearing into wild-type mice led to the induction of retinopathy in 4/16 animals. We suggest that melanoma-associated retinopathy can be mediated by humoral and/or cellular immune responses against a number of cancer-retina antigens which may function as paraneoplastic antigens in melanoma-associated retinopathy.     

Torque teno virus in liver diseases: On the way towards unity of view

The review presents the data accumulated for more than 20 years of research of torque teno virus(TTV). Its molecular genetic structure, immunobiology,epidemiology, diagnostic methods, possible replication sites, and pathogenicity factors are described. TTV is a virus that is frequently detectable in patients with different viral hepatitides, in cases of hepatitis without an obvious viral agent, as well as in a healthy population. There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection. There are sufficient histological signs of liver damage, which confirm that the virus can undergo a replicative cycle in hepatocytes. Along with this, cytological hybridization in TTV-infected cells has shown no substantial cytopathic(cell-damaging) effects that are characteristic of pathogenic hepatotropic viruses. Studying TTV has led to the evolution of views on its role in the development of human pathology. The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses, including the viruses of the known types of hepatitides. The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a nonpathogenic virus. It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body's immune status. The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses. Fortunately, the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties. The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study.     

Hypotensive and Hepatoprotective Properties of the Polysaccharide-Stabilized Foaming Composition Containing Hydrolysate of Whey Proteins

Whey protein hydrolysates (WPHs) are one of the most promising sources of biofunctional peptides with such beneficial properties as antioxidant, antihypertensive, anti-inflammatory and others. WPHs also could be used as foaming agents for aerated products (e.g., milk shake type drinks). However, WPH alone has a bitter taste and foamed WPH should be stabilized by additional ingredients. Here, we present a composition including WPH and three polysaccharides—pumpkin pectin, sodium alginate and ι-carrageenan—used as foam stabilizers. Polysaccharide content was selected according to foaming, organoleptic antioxidant and angiotensin-I-converting enzyme inhibitory characteristics of the resulted composition. Further, the hypotensive, antioxidant and hepatoprotective properties of the composition were proved by in vivo tests performed in spontaneously hypertensive rats and Wistar rats with CCl₄-induced hepatic injury.     

Development of novel biological resection criteria for safe and oncologically satisfying resection of hepatocellular carcinoma

Objective

To develop criteria for safe and oncologically satisfying liver resection in case of early hepatocellular carcinoma with a 5-year overall survival (OS) similar to liver transplantation.

ε-Aminocaproic Acid Esters as Transdermal Penetration Enhancing Agents

The synthesis of -aminocaproic acid esters is described. Two representative members from a group of five of the 1-alkyl homologues synthetized as flexible analogues of 1-alkylazacycloheptanone derivatives were evaluated in vitro for their effectiveness on the transport of theophylline through the excised human cadaver skin in comparison with Azone. The 1-octyl- and 1-dodecyl--aminocaproic acid esters (OCEAC and DDEAC) show excellent penetration enhancement. Donor samples contained 2.5% theophylline and 1% enhancers tested in three different vehicles. Fluxes of theophylline were increased with OCEAC about 19 times from olive oil, 45 times from water, and about 38 times from water–propylene glycol (3:2) vehicle toward controls (with DDEAC about 17, 39, and 35 times, respectively) and they were markedly higher than Azone under the given conditions. Acute LD₅₀'s (i.p. in mice) of OCEAC (DDEAC) were 245 mg/kg (352 mg/kg), with a slightly lower toxicity than Azone. OCEAC and DDEAC did not exhibit acute dermal irritation in vivo on rabbits at a 5% concentration in white petrolatum.     

Mixed epithelial/mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast in BRCA1 carrier

This case report describes a 35-year-old woman who was diagnosed with mixed epithelial/mesenchymal metaplastic carcinoma (carcinosarcoma) of the breast. Genetic analysis of blood DNA revealed a common founder mutation, BRCA1 5382insC. Examination of microdissected tumor samples determined that both epithelial and mesenchymal components contained deletion of the wild-type BRCA1 allele. This report exemplifies that even very uncommon breast tumor types may develop through biallelic inactivation of BRCA1 gene, that has to be considered in the genetic testing settings.     

Obesity – a social and physical risk

Overweight and obesity are an accepted cause of numerous metabolic disor‐ders. The obvious strategies for prevention and therapy of increased fat body mass (reduction of energy intake, increase of physical activity) fail in most cases, especially with respect to their sustainability. The lack of success of programs developed so far for prevention and therapy of obesity suggests the existence of poorly‐understood regulatory mechanisms leading to the imbalance between energy uptake and energy expenditure. Besides physiological factors,such as dysregulated levels of hunger‐controlling or satiation‐mediating hormones, the composition of the intestinal flora and synthetic compounds with hormone‐like activity have been suggested as triggers of the development of obesity. Along with biological and metabolic parameters, scientists have focused more and more on psychological and sociological factors in the development of a strategy for the prevention of obesity. Important factors in this context are the motivation and ability to self‐regulation and aspects of the socio‐cultural context. Consequently, the real challenge in reducing the prevalence of obesity is not only the identification of relevant parameters but also the assessment of proportionality of these factors. To achieve this goal, borders of disciplines dealing with obesity development (nutrition, medicine, kinematics, psychology, sociology) need to be overcome. Common models must be developed that facilitate the assessment of both the importance of single factors and their relationship to each other.     

Case Study of Polyvinylidene Fluoride Doping by Carbon Nanotubes

Modern material science often makes use of polyvinylidene fluoride thin films because of various properties, like a high thermal and chemical stability, or a ferroelectric, pyroelectric and piezoelectric activity. Fibers of this polymer material are, on the other hand, much less explored due to various issues presented by the fibrous form. By introducing carbon nanotubes via electrospinning, it is possible to affect the chemical and electrical properties of the resulting composite. In the case of this paper, the focus was on the further improvement of interesting polyvinylidene fluoride properties by incorporating carbon nanotubes, such as changing the concentration of crystalline phases and the resulting increase of the dielectric constant and conductivity. These changes in properties have been explored by several methods that focused on a structural, chemical and electrical point of view. The resulting obtained data have been documented to create a basis for further research and to increase the overall understanding of the properties and usability of polyvinylidene fluoride fiber composites.     

Smoking is an independent risk factor for oncogenic human papillomavirus (HPV) infections but not for high-grade CIN

Background Recent evidence implicates smoking as a risk factor for cervical cancer (CC), but the confounding from high-risk human papillomavirus (HPV) infections is not clear. Objectives To analyse the role of smoking as an independent predictor of CIN2+ and HR-HPV infections in a population-based prospective (NIS, New Independent States of former Soviet Union) cohort study. Study design and Methods A cohort of 3,187 women was stratified into three groups according to their smoking status: (i) women who never smoked; (ii) those smoking in the past; and (iii) women who are current smokers. These groups were analysed for predictors of (a) HR-HPV; (b) high-grade CIN, and (c) outcome of HR-HPV infections and cytological abnormalities during prospective follow-up (n = 854). Results The three groups were significantly different in all major indicators or risk sexual behaviour (or history) implicating strong confounding. There was no increase in HSIL/LSIL/ASC-US cytology or CIN1+/CIN2+/CIN3+ among current smokers. Only few predictors of HR-HPV and CIN2+ were common to all three groups, indicating strong interference of the smoking status. There was no difference in outcomes of cervical disease or HR-HPV infections between the three groups. In multivariate model, being current smoker was one of the five independent predictors of HR-HPV (P = 0.014), with adjusted OR = 1.52 (95%CI 1.09–2.14). In addition to age, HR-HPV was the only independent predictor of CIN2+ in multivariate model (OR = 14.8; 95%CI 1.72–127.31). Conclusions These data indicate that cigarette smoking is not an independent risk factor of CIN2+, but the increased risk ascribed to smoking is mediated by acquisition of HR-HPV, of which current smoking was an independent predictor in multivariate model.     

Renal Denervation—Hypes and Hopes

Catheter‐based renal denervation (RDN) is a novel invasive approach in the treatment of resistant hypertension. It is considered a minimally invasive and safe procedure which, as shown by initial experimental and clinical trials, is able not only to reduce blood pressure but also to modify its risk factors by modulation of autonomic nervous system. Recently published results of a randomized Symplicity HTN‐3 trial, which failed to demonstrate RDN‐induced reduction of blood pressure at six months, decreased the initial enthusiasm regarding RDN and raised a question about real efficacy of this procedure. Nevertheless, still there are some other conditions characterized by increased sympathetic tone such as heart failure, atrial fibrillation, or ventricular arrhythmias that may benefit from RDN. Furthermore, novel therapeutical approach toward RDN using adapted electrophysiological or new specially designed electrodes may improve effectiveness of RDN procedure.