Relationship between formaldehyde exposure, respiratory irritant effects and cancers: a review of reviews.

OBJECTIVES: Formaldehyde is an organic compound used in the production of resins, paper, wood plywood, solvents and cleaning products. Formaldehyde is also present when tobacco is smoked. Formaldehyde has been defined as an irritant and is classified as a human carcinogen by the International Agency for Research on Cancer. The purpose of this study was to demonstrate the following two distinct correlations: (1) the association between formaldehyde exposure and development of irritant diseases affecting the respiratory tract, mainly asthma; and (2) the association between formaldehyde exposure and development of neoplastic diseases. STUDY DESIGN: This was an umbrella review. METHODS: A search was conducted in the three main electronic databases of scientific literature: PubMed, Scopus and Web of Science. The search included systematic reviews and meta-analyses published in the previous 10 years. Initially, titles and abstracts of retrieved articles were evaluated, then full-text assessments of selected articles took place. Data extraction and quality assessment were performed according to Assessing the Methodological Quality of Systematic Reviews (AMSTAR) score. RESULTS: A total of 630 articles were initially collected. Nine articles concerning the association between formaldehyde exposure and asthma were included in the present review, and the majority of these reported good association. In addition, 27 articles investigating the association between formaldehyde exposure and neoplastic diseases were included in the review. These studies showed that nasopharyngeal cancer and leukaemia were the most represented neoplastic diseases; however, only a weak association was reported between formaldehyde exposure and cancer. CONCLUSIONS: Although the studies included in this review did not show a strong association between exposure to formaldehyde and irritant or neoplastic diseases, the World Health Organisation recommends that levels of formaldehyde do not exceed the threshold value of 0.1 mg/m3 (0.08 ppm) for a period of 30 min. It is recommended that preventive measures, such as ventilation in workplaces with high exposure to formaldehyde and environmental monitoring of formaldehyde concentrations, are implemented.

Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced obesity.

PURPOSE: Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional pharmacological approaches. New strategies based on natural remedies are under continuous investigation. Leopoldia comosa (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified. The aim of this study was to evaluate the effects of a diet supplemented with L. comosa extracts on a rat model of diet-induced obesity. METHODS: Leopoldia comosa bulb extracts were obtained using a dynamic extractor. Phytochemical properties and in vitro determination of the antioxidant activity and of the inhibitory effects on lipase and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet, or a high-fat diet (HFD), or an HFD plus L. comosa (20 or 60 mg/die) extracts. The metabolic and anthropometric parameters were recorded. RESULTS: Results indicated that L. comosa inhibited lipase and pancreatic amylase activities. In vivo data showed that the supplementation with both doses of L. comosa extracts counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity and dyslipidemia, and improved glucose tolerance with a reduction of lipidic tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver, L. comosa reduced protein expression levels of PEPCK and G6Pase. CONCLUSION: We suggest that L. comosa extracts prevent obesity-dependent metabolic disorders. This paves the way for their therapeutic application as a natural anti-obesity drug.

Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection.

Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood-brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R). By ELISA the presence of PNX was detected in both hypothalamus and heart. In plasma of normal, but not of obese rats, the peptide concentrations increased after meal. Exposure of the isolated and Langendorff perfused rat heart to exogenous PNX induces a reduction of contractility and relaxation, without effects on coronary pressure and heart rate. As revealed by immunoblotting, these effects were accompanied by an increase of Erk1/2, Akt and eNOS phosphorylation. PNX (EC50 dose), administered after ischemia, induced post-conditioning-like cardioprotection. This was revealed by a smaller infarct size and a better systolic recovery with respect to those detected on hearts exposed to I/R alone. The peptide also activates the cardioprotective RISK and SAFE cascades and inhibits apoptosis. These effects were also observed in the heart of obese rats. Our data provide a first evidence on the peripheral activity of PNX and on its direct cardiomodulatory and cardioprotective role under both normal conditions and in the presence of metabolic disorders.

The innovative "Bio-Oil Spread" prevents metabolic disorders and mediates preconditioning-like cardioprotection in rats.

BACKGROUND AND AIMS: Obesity is often associated with an increased cardiovascular risk. The food industry and the associated research activities focus on formulating products that are a perfect mix between an adequate fat content and health. We evaluated whether a diet enriched with Bio-Oil Spread (SD), an olive oil-based innovative food, is cardioprotective in the presence of high-fat diet (HFD)-dependent obesity. METHODS AND RESULTS: Rats were fed for 16 weeks with normolipidic diet (ND; fat: 6.2%), HFD (fat: 42%), and ND enriched with SD (6.2% of fat + 35.8% of SD). Metabolic and anthropometric parameters were measured. Heart and liver structures were analyzed by histochemical examination. Ischemic susceptibility was evaluated on isolated and Langendorff-perfused cardiac preparations. Signaling was assessed by Western blotting. Compared to ND rats, HFD rats showed increased body weight and abdominal obesity, dyslipidemia, and impaired glucose tolerance. Morphological analyses showed that HFD is associated with heart and liver modifications (hypertrophy and steatosis, respectively), lesser evident in the SD group, together with metabolic and anthropometric alterations. In particular, IGF-1R immunodetection revealed a reduction of hypertrophy in SD heart sections. Notably, SD diet significantly reduced myocardial susceptibility against ischemia/reperfusion (I/R) with respect to HFD through the activation of survival signals (Akt, ERK1/2, and Bcl2). Systolic and diastolic performance was preserved in the SD group. CONCLUSIONS: We suggest that SD may contribute to the prevention of metabolic disorders and cardiovascular alterations typical of severe obesity induced by an HFD, including the increased ischemic susceptibility of the myocardium. Our results pave the way to evaluate the introduction of SD in human alimentary guidelines as a strategy to reduce saturated fat intake.

The NO stimulator, Catestatin, improves the Frank-Starling response in normotensive and hypertensive rat hearts.

The myocardial response to mechanical stretch (Frank-Starling law) is an important physiological cardiac determinant. Modulated by many endogenous substances, it is impaired in the presence of cardiovascular pathologies and during senescence. Catestatin (CST:hCgA352-372), a 21-amino-acid derivate of Chromogranin A (CgA), displays hypotensive/vasodilatory properties and counteracts excessive systemic and/or intra-cardiac excitatory stimuli (e.g., catecholamines and endothelin-1). CST, produced also by the myocardium, affects the heart by modulating inotropy, lusitropy and the coronary tone through a Nitric Oxide (NO)-dependent mechanism. This study evaluated the putative influence elicited by CST on the Frank-Starling response of normotensive Wistar-Kyoto (WKY) and hypertensive (SHR) hearts by using isolated and Langendorff perfused cardiac preparations. Functional changes were evaluated on aged (18-month-old) WKY rats and SHR which mimic human chronic heart failure (HF). Comparison to WKY rats, SHR showed a reduced Frank-Starling response. In both rat strains, CST administration improved myocardial mechanical response to increased end-diastolic pressures. This effect was mediated by EE/IP3K/NOS/NO/cGMP/PKG, as revealed by specific inhibitors. CST-dependent positive Frank-Starling response is paralleled by an increment in protein S-Nitrosylation. Our data suggested CST as a NO-dependent physiological modulator of the stretch-induced intrinsic regulation of the heart. This may be of particular importance in the aged hypertrophic heart, whose function is impaired because of a reduced systolic performance accompanied by delayed relaxation and increased diastolic stiffness.

Primary HPV test screening in cervical cancer: a two-year experience of a single screening center in Latina (Italy).

OBJECTIVE: The aim of this study was to evaluate the effect and performance of the new algorithm in cervical cancer screening program in two years' experience of Latina (Italy). MATERIALS AND MTHODS: The female population was divided into two groups, the first group was referred to PAP test and the second one to hr-HPV test according to national guidelines. RESULTS: In two years the participation mean rate increased among women aged 35-64 compared to women aged 25-34. The primary PAP test positive rate and hr-HPV test positive rate were 4.0% and 5.2%, respectively. The PAP test positive rate among hr-HPV+ women decreased from 2012 to 2013. Women with hr-HPV+/PAP+ were referred immediately to colposcopy and this rate was 1.2%. The predictive positive value for CIN2+ to colposcopy was 10.9% in 2012 and 9.1% in 2013, while the detection rate for CIN2+ was 1.6% in 2012 and 1.4% in 2013. CONCLUSION: The stratification of the female population leads to a decreased inappropriate therapeutic path while the combination of hr-HPV test with PAP test in woman aged 35-64 lets obtain high levels specificity and sensitivity results.

The 16, 18, and 45 HPV infection in high grade squamous cervical lesions in primary hr-HPV test screening program.

Infection with high-risk human papillomavirus (hr-HPV) 16, 18, and 45 causes 94% of cervical carcinoma. In the present screening center the authors perform the hr-HPV test followed by Pap test to women aged 35-64 years if they result hr-HPV+. The authors' aimed to provide data regarding the genotyping test and eventually to propose this test as alternative to triage cytology. They used a genotyping test to identify HPV 16, 18, and 45 in 22 women with histological diagnosis of CIN2+, 22 women with histological diagnosis of CIN1 and 22 women hr-HPV+/Pap-. The group of CIN2+ showed the higher positivity to the test and the higher positivity to HPV 16 than other groups. Analyzing the clinical performance of the genotyping test the authors observed that the specificity was 64%. From these data they concluded that the identification of HPV 16 is predictive for high-grade lesions but this test could not be used alternatively to triage cytology.

rAAV9 combined with renal vein injection is optimal for kidney-targeted gene delivery: conclusion of a comparative study.

Effective gene therapy strategies for the treatment of kidney disorders remain elusive. We report an optimized kidney-targeted gene delivery strategy using recombinant adeno-associated virus (rAAV) administered via retrograde renal vein injection in mice. Renal vein injection of rAAV consistently resulted in superior kidney transduction compared with tail vein injection using as little as half the tail vein dose. We compared rAAV5, 6, 8 and 9, containing either green fluorescent protein (GFP) or luciferase reporter genes driven by the Cytomegalovirus promoter. We demonstrated that although rAAV6 and 8 injected via renal vein transduced the kidney, transgene expression was mainly restricted to the medulla. Transgene expression was systematically low after rAAV5 injection, attributed to T-cell immune response, which could be overcome by transient immunosuppression. However, rAAV9 was the only serotype that permitted high-transduction efficiency of both the cortex and medulla. Moreover, both the glomeruli and tubules were targeted, with a higher efficiency within the glomeruli. To improve the specificity of kidney-targeted gene delivery with rAAV9, we used the parathyroid hormone receptor 'kidney-specific' promoter. We obtained a more efficient transgene expression within the kidney, and a significant reduction in other tissues. Our work represents the first comprehensive and clinically relevant study for kidney gene delivery.

Neuropeptide Y reduces the expression of PLCB2, PLCD1 and selected PLC genes in cultured human endothelial cells.

Endothelial cells (EC) are the first elements exposed to mediators circulating in the bloodstream, and react to stimulation with finely tuned responses mediated by different signal transduction pathways, leading the endothelium to adapt. Neuropeptide Y (NPY), the most abundant peptide in heart and brain, is mainly involved in the neuroendocrine regulation of the stress response. The regulatory roles of NPY depend on many factors, including its enzymatic processing, receptor subtypes and related signal transduction systems, including the phosphoinositide (PI) pathway and related phospholipase C (PI-PLC) family of enzymes. The panel of expression of PI-PLC enzymes differs comparing quiescent versus differently stimulated human EC. Growing evidences indicate that the regulation of the expression of PLC genes, which codify for PI-PLC enzymes, might act as an additional mechanism of control of the PI signal transduction pathway. NPY was described to potentiate the activation of PI-PLC enzymes in different cell types, including EC. In the present experiments, we stimulated human umbilical vein EC using different doses of NPY in order to investigate a possible role upon the expression PLC genes. NPY reduced the overall transcription of PLC genes, excepting for PLCE. The most significant effects were observed for PLCB2 and PLCD1, both isoforms recruited by means of G-proteins and G-protein-coupled receptors. NPY behavior was comparable with other PI-PLC interacting molecules that, beside the stimulation of phospholipase activity, also affect the upcoming enzymes' production acting upon gene expression. That might represent a mode to regulate the activity of PI-PLC enzymes after activation.

Expression of phosphoinositide-specific phospholipase C enzymes in human skin fibroblasts.

Fibroblasts are involved in a number of functions regulated by different signal transduction pathways, including the phosphoinositide (PI) signaling system and related converting enzymes, such as phosphoinositide-specific phospholipase C (PI-PLC). The PI-PLC family comprises crucial effector enzymes in the PI signal transduction pathway. Once activated, PI-PLC cleaves an important membrane PI, the phosphatidylinositol (4,5) bisphosphate into inositol trisphosphate and diacylglycerol-both are crucial molecules in the transduction of signals. The activity of selected PI-PLC enzymes was reported in fibroblasts, although the complete panel of expression was not available. Each cell type expresses a group of selected PI-PLC isoforms, and knowledge of the panel of expression is a necessary and preliminary tool to address further studies. In the present study, we delineated the expression panel of PI-PLC enzymes in human skin fibroblasts. PI-PLC ß1, PI-PLC ß3, PI-PLC ß4, PI-PLC γ1, PI-PLC γ2, PI-PLC δ1, PI-PLC δ3, PI-PLC δ4, and PI-PLC ϵ were expressed. PI-PLC ß1 was weakly expressed, PI-PLC δ4 was inconstantly expressed, and PI-PLC γ2 was weakly expressed.

Unsafe abortion after legalisation in Nepal: a cross-sectional study of women presenting to hospitals.

OBJECTIVE: To investigate abortion practices of Nepali women requiring postabortion care. DESIGN: Cross-sectional study. SETTING: Four tertiary-care hospitals in urban and rural Nepal. SAMPLE: A total of 527 women presenting with complications from induced abortion in 2010. METHODS: Women completed questionnaires on their awareness of the legal status of abortion and their abortion-seeking experiences. The method of induction and whether the abortion was obtained from an uncertified source was documented. Multivariable logistic regression was used to identify associated factors. MAIN OUTCOME MEASURES: Induction method; uncertified abortion source. RESULTS: In all, 234 (44%) women were aware that abortion was legal in Nepal. Medically induced abortion was used by 359 (68%) women and, of these, 343 (89%) took unsafe, ineffective or unknown substances. Compared with women undergoing surgical abortion, women who had medical abortion were more likely to have obtained information from pharmacists (161/359, 45% versus 11/168, 7%, adjusted odds ratio [aOR] 8.1, 95% confidence interval 4.1-16.0) and to have informed no one about the abortion (28/359, 8% versus 3/168, 2%, aOR 5.5, 95% CI 1.1-26.9). Overall, 291 (81%) medical abortions and 50 (30%) surgical abortions were obtained from uncertified sources; these women were less likely to know that abortion was legal (122/341, 36% versus 112/186, 60%, aOR 0.4, 95% CI 0.2-0.7) and more likely to choose a method because it was available nearby (209/341, 61% versus 62/186, 33%, aOR 2.5, 95% CI 1.5-4.3), compared with women accessing certified sources. CONCLUSIONS: Among women presenting to hospitals in Nepal with complications following induced abortion of pregnancy, the majority had undergone medically induced abortions using unknown substances acquired from uncertified sources. Women using medications and those accessing uncertified providers were less aware that abortion is now legal in Nepal. These findings highlight the need for continued improvements in the provision and awareness of abortion services in Nepal.

Growth factors, their receptor expression and markers for proliferation of endothelial and neoplastic cells in human osteosarcoma.

Osteosarcoma is the most common primary malignant tumour of the bone. Although new therapies continue to be reported, osteosarcoma-related morbidity and mortality remain high. Modern medicine has greatly increased knowledge of the physiopathology of this neoplasm. Novel targets for drug development may be identified through an understanding of the normal molecular processes that are deeply modified in pathological conditions. The aim of the present study is to investigate, by immunohistochemistry, the localisation of different growth factors and of the proliferative marker Ki-67 in order to determine whether these factors are involved in the transformation of osteogenic cells and in the development of human osteosarcoma. We observed a general positivity for NGF - TrKA - NT3 - TrKC - VEGF in the cytoplasm of neoplastic cells and a strong expression for NT4 in the nuclear compartment. TGF-beta was strongly expressed in the extracellular matrix and vascular endothelium. BDNF and TrKB showed a strong immunolabeling in the extracellular matrix. Ki-67/MIB-1 was moderately expressed in the nucleus of neoplastic cells. We believe that these growth factors may be considered potential therapeutic targets in the treatment of osteosarcoma, although proof of this hypothesis requires further investigation.

Heavy metals in human amniotic fluid: a pilot study.

OBJECTIVE: Many heavy metals are essential nutrients for a healthy life. However, significant evidence supports prolonged prenatal exposure as a risk factor for several adverse health effects. The aim of this study is to evaluate the presence of heavy metals in human amniotic fluid (AF) to demonstrate that there is an early fetal in utero exposure. METHODS: The concentrations of a variety of heavy metals, including Be, Ag, Ba, Pb, U, Hg, Sr, Cu, Mn, V, Pd, Sn, Sb, Te, Pt, Sc, Tl, Ni, As, Co, Zn and Se, were measured in 25 AF samples obtained from amniocentesis between 15 and 18 weeks of gestational, after informed consent. RESULTS: Be, Ag, Ba, Pb, U, Cu, Sr, Mn, V, Sn, Te, Pt, As, Tl, Sb, Co, Se and Zn concentrations were detected in measurable amounts in second trimester AF. Mg levels are elevated in all samples. Pd, Ni, Sc and Hg concentrations are below the detection limits in all samples. CONCLUSION: This study demonstrates that heavy metals pass into and accumulate in AF from a very early stage of gestation. Other studies are needed to evaluate the long-term health effects of this early exposure.

Rotator cuff re-tear or non-healing: histopathological aspects and predictive factors.

PURPOSE: The aim of the study was to evaluate the histopathological changes that occur in the tendon and subacromial bursal tissue in patients with rotator cuff tear trying to correlate these changes to their healing capability. METHODS: Eighty-four patients were clinically evaluated with the Constant Scale. Radiographs and MRI were performed preoperatively and ultrasound were performed postoperatively. For each patient, a biopsy of the supraspinatus tendon and subacromial bursa was performed, and the specimens were histopathologically analyzed. RESULTS: Tendons histopathological features consisted of loss of structural organization, poor or absent neoangiogenesis, chondral metaplasia, and fibrosis. Bursal features consisted of neoangiogenesis, absence of chondral metaplasia, hyperplasia/hypertrophy, and absence of necrosis. Direct correlation was seen between tendon and bursal hyperplasia and time of the onset of symptoms; between tendon chondral metaplasia, fibrosis, bursal neoangiogenesis, inflammation, and patient age; between tendon neoangiogenesis, hyperplasia, necrosis, fibrosis, bursal necrosis, inflammation, and lesion size; on the contrary, tendon fibrosis, necrosis, and bursal tissue inflammation decrease as time passes from the onset of symptoms. Tendon fibers disarray, neoangiogenesis, and inflammation decreases as the patient's age increases. Bursal tissue fibrosis decreases as lesion size increases. CONCLUSIONS: Simple histopathological techniques should be employed routinely to assess the tissue quality, with the aim to predict future clinical evolution (repair or non-repair). Comparing the histopathological data with the demographical information and the descriptive statistics, it is possible to define the RCT repair at risk and identify which RCT will be able to heal.

Nutrition education in medical schools (NEMS) project: Joining ESPEN and university point of view.

BACKGROUND & AIMS: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. RESULTS: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. CONCLUSION: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).

Mesenchymal cystic hamartoma presenting with pneumothorax: case report and review of the literature.

Mesenchymal cystic hamartoma (MCH) of the lung is a rare disease, with an indolent course in the majority of cases. It can be single or multifocal and it is composed of primitive mesenchymal cells admixed with cystic spaces. Only few cases have been reported in the literature, with variable clinical presentation. We describe the case of a huge MCH, presenting with spontaneous pneumothorax in a 65-year-old man. Further, we provide a brief overview of the literature and discuss the differential diagnosis with other entities, and the possible diagnostic pitfalls.

COVID-19-associated cardiovascular morbidity in older adults: a position paper from the Italian Society of Cardiovascular Researches.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19). SARS-CoV-2 causes viral pneumonia with additional extrapulmonary manifestations and major complications, including acute myocardial injury, arrhythmia, and shock mainly in elderly patients. Furthermore, patients with existing cardiovascular comorbidities, such as hypertension and coronary heart disease, have a worse clinical outcome following contraction of the viral illness. A striking feature of COVID-19 pandemics is the high incidence of fatalities in advanced aged patients: this might be due to the prevalence of frailty and cardiovascular disease increase with age due to endothelial dysfunction and loss of endogenous cardioprotective mechanisms. Although experimental evidence on this topic is still at its infancy, the aim of this position paper is to hypothesize and discuss more suggestive cellular and molecular mechanisms whereby SARS-CoV-2 may lead to detrimental consequences to the cardiovascular system. We will focus on aging, cytokine storm, NLRP3/inflammasome, hypoxemia, and air pollution, which is an emerging cardiovascular risk factor associated with rapid urbanization and globalization. We will finally discuss the impact of clinically available CV drugs on the clinical course of COVID-19 patients. Understanding the role played by SARS-CoV2 on the CV system is indeed mandatory to get further insights into COVID-19 pathogenesis and to design a therapeutic strategy of cardio-protection for frail patients.

Conservative model for synchronization problems in complex networks.

In this paper we study the scaling behavior of the interface fluctuations (roughness) for a discrete model with conservative noise on complex networks. Conservative noise is a noise which has no external flux of deposition on the surface and the whole process is due to the diffusion. It was found that in Euclidean lattices the roughness of the steady state W(s) does not depend on the system size. Here, we find that for scale-free networks of N nodes, characterized by a degree distribution P(k) approximately k(-lambda), W(s) is independent of N for any lambda. This behavior is very different than the one found by Pastore y Piontti [Phys. Rev. E 76, 046117 (2007)] for a discrete model with nonconservative noise, which implies an external flux, where W(s) approximately ln N for lambda<3 , and was explained by nonlinear terms in the analytical evolution equation for the interface [La Rocca, Phys. Rev. E 77, 046120 (2008)]. In this work we show that in these processes with conservative noise the nonlinear terms are not relevant to describe the scaling behavior of W(s).

Atrial fibrillation in pure rheumatic mitral valvular disease is expression of an atrial histological change.

BACKGROUND: Some of theories try to explain the insurgence of atrial fibrillation (AF) in patients with acute articular rheumatism (AAR). These theories remind the close relation between AF and left atrium, or with valvular vitium degree, or monophasic action potential and histological cardiac structure. In 15 years of work in the academic Department of Heart and Big Vessels in Rome, the Authors studied 243 patients with mitral valvular disease post AAR before and after surgical manoeuvres. MATERIALS AND METHODS: Patients were divided in order to monitor atrium and ventricle morphological and functional modifications of the valve according to cardiac rhythm. Patients classification was based on surgical therapy adopted, kind of mitral disease and cardiac rhythm. An histological examination was performed, only in patients treated with valvular replacement. During the operation an histological examination in an atrial tissue fragment was performed. 243 patients with mitral valvular disease post AAR with indication in valvular adjustment were studied. The whole population was treated with mitral transcutaneous valvuloplasty (Group B--130 patients) or with mitral valve replacement surgery (Group A--113 patients). These two groups were divided: in Gr.A in Gr.A1 and Gr.A2, and Gr.B in Gr.B1 and Gr.B2, according to cardiac rhythm (sinus rhythm iSR, AF). These subgroups were also divided in Gr.A1SR, Gr.A1AF; Gr.A2SR, Gr.A2AF; Gr.A3SR, Gr.A3AF, according to mitralic disease's kind (stenosis, stenosis/regurgitation, regurgitation). A complex screening were exerted to all patients using echocardio-doppler technology. Morphological parameters of atrium and ventricle, and functional parameters of mitral valve, aorta and tricuspid were evaluated. In Gr.A group patients during the operation were execute a bioptic sampling from left atrium and a consecutive histological valuation. RESULTS: In Gr.A1 mitral valve area (MtVA) arises smaller (p<0.01) in the group with AF, than those in SR. On the contrary, in subgroups of population of Gr.B there isn't statistic disagreement (p>0.05). Left atrium volume arises elder in patients in AF than in patients in SR (p<0.01), either in patients of subgroups Gr.A1, Gr.A2 or in patients of the whole Gr.B before and after valvuloplasty. In the whole population Gr.B, either Gr.BRS or Gr.BFA, left and right atrial volumes decrease eloquently (p<0.01) after valvoplasty. There's no linear relationship (Pearson r<0.5) between the different subgroups of Gr.A (Gr.A1, Gr.A2, Gr.A3) and those of Gr.B according to mitral valve area (MtVA), volume and left atrial area. Left atrial biopsy shows in patients of SR a normal atrial tissue in the 48% of cases and lightly altered in remaining 52%. On the contrary in patients of AF there are strong anomalies in the 100% of cases. CONCLUSIONS: According to histological view, atrial volumes variations and valvular area variations before and after surgical treatment, and according also to their comparisons in different groups, authors could assume that insurgence of AF and its chronicization could be an expression of a strong atrial myocardial histological alteration. Furthermore while starting moment of AF genesis is characterized by histological alterations of atrial myocardium (expression of rheumatic chronic disease), its chronicization hands to anatomic-volumetric progressive deterioration of the atrial dysfunction.

Gene Transfer to Mouse Kidney In Vivo.

Genetic nephropathies represent a challenging class of disorders to be treated by gene therapy. This is primarily due to the filtering properties of the kidney itself, which does not allow the vehicle carrying the transgene of interest to remain long enough in the organ to penetrate efficiently into the nephrotic cells. Also, the kidney has a complex anatomical structure composed of different cell types compartmentalized within isolated anatomic structures that limit their access. Here, we describe a simple surgical procedure to deliver recombinant adeno-associated virus (rAAV) to the whole kidney based on the hydraulic force of the retrograde renal vein injection. In its clinical form, this procedure would correspond to a renal venography where a catheter is threaded retrograde from the femoral vein under fluoroscopic guidance.