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.

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.

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.

Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency.

Genome editing is the introduction of directed modifications in the genome, a process boosted to therapeutic levels by designer nucleases. Building on the experience of ex vivo gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of ex vivo gene-edited Prkdc scid HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by ex vivo genome editing followed by transplantation, and highlight some of the challenges.

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.

Hematopoietic Stem Cells Transplantation Can Normalize Thyroid Function in a Cystinosis Mouse Model.

Hypothyroidism is the most frequent and earliest endocrine complication in cystinosis, a multisystemic lysosomal storage disease caused by defective transmembrane cystine transporter, cystinosin (CTNS gene). We recently demonstrated in Ctns(-/-) mice that altered thyroglobulin biosynthesis associated with endoplasmic reticulum stress, combined with defective lysosomal processing, caused hypothyroidism. In Ctns(-/-) kidney, hematopoietic stem cell (HSC) transplantation provides long-term functional and structural protection. Tissue repair involves transfer of cystinosin-bearing lysosomes from HSCs differentiated as F4/80 macrophages into deficient kidney tubular cells, via tunneling nanotubes that cross basement laminae. Here we evaluated the benefit of HSC transplantation for cystinotic thyroid and investigated the underlying mechanisms. HSC engraftment in Ctns(-/-) thyroid drastically decreased cystine accumulation, normalized the TSH level, and corrected the structure of a large fraction of thyrocytes. In the thyroid microenvironment, HSCs differentiated into a distinct, mixed macrophage/dendritic cell lineage expressing CD45 and major histocompatibility complex II but low CD11b and F4/80. Grafted HSCs closely apposed to follicles and produced tunneling nanotube-like extensions that crossed follicular basement laminae. HSCs themselves further squeezed into follicles, allowing extensive contact with thyrocytes, but did not transdifferentiate into Nkx2.1-expressing cells. Our observations revealed significant differences of basement lamina porosity between the thyroid and kidney and/or intrinsic macrophage invasive properties once in the thyroid microenvironment. The contrast between extensive thyrocyte protection and low HSC abundance at steady state suggests multiple sequential encounters and/or remanent impact. This is the first report demonstrating the potential of HSC transplantation to correct thyroid disease and supports a major multisystemic benefit of stem cell therapy for cystinosis.

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.

Ezrin-related Phosphoinositide pathway modifies RhoA and Rac1 in human osteosarcoma cell lines.

Selected Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes occupy the convergence point of the broad range of pathways that promote Rho and Ras GTPase mediated signalling, which also regulate the activation of ezrin, a member of the ezrin-radixin-moesin (ERM) proteins family involved in the metastatic osteosarcoma spread. Previous studies described that in distinct human osteosarcoma cell lines ezrin networks the PI-PLC with complex interplay controlling the expression of the PLC genes, which codify for PI-PLC enzymes. In the present study, we analyzed the expression and the sub-cellular distribution of RhoA and Rac1 respectively after ezrin silencing and after PI-PLC ε silencing, in order to investigate whether ezrin-RhoGTPAses signalling might involve one or more specific PI-PLC isoforms in cultured 143B and Hs888 human osteosarcoma cell lines. In the present experiments, both ezrin and PLCE gene silencing had different effects upon RhoA and Rac1 expression and sub-cellular localization. Displacements of Ezrin and of RhoA localization were observed, probably playing functional roles.

Impairment and reorganization of the phosphoinositide-specific phospholipase C enzymes in suicide brains.

A number of studies suggested that suicide may be associated with specific neurobiological abnormalities. Neurobiology studies focused upon abnormalities of signalling mechanisms with special regard to the serotonin system and the related Phosphoinositide (PI) signalling system. Previous data suggested the involvement of the PI-specific phospholipase C (PLC) family in neuropsychiatric disorders. By using PCR and morphological microscopy observation we examined the whole panel of expression of PLC isoforms in the brains of 28 individuals who committed suicide and in normal controls in order to evaluate the involvement of specific PLC isoforms. The overall PLC expression was reduced and a complex reorganization of the isoforms was observed. The knowledge of the complex network of neurobiological molecules and interconnected signal transduction pathways in the brain of suicide victims might be helpful to understand the natural history and the pathogenesis of the suicidal behavior. That might lead to obtain prognostic suggestions in order to prevent suicide and to new therapeutic agents targeting specific sites in this signalling cascade.

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.

Ezrin silencing remodulates the expression of Phosphoinositide-specific Phospholipase C enzymes in human osteosarcoma cell lines.

Ezrin, a protein belonging to the Ezrin, radixin and moesin (ERM) family, was engaged in the metastatic spread of osteosarcoma. The Protein 4.1, Ezrin, radixin, moesin (FERM) domain of Ezrin binds the membrane Phosphatydil inositol (4,5) bisphosphate (PIP2), a crucial molecule belonging to the Phosphoinositide (PI) signal transduction pathway. The cytoskeleton cross-linker function of Ezrin largely depends on membrane PIP2 levels, and thus upon the activity of related enzymes belonging to the PI-specific phospholipase C (PI-PLC) family. Based on the role of Ezrin in tumour progression and metastasis, we silenced the expression of Vil2 (OMIM *123900), the gene which codifies for Ezrin, in cultured human osteosarcoma 143B and Hs888 cell lines. After Ezrin silencing, the growth rate of both cell lines was significantly reduced and morphogical changes were observed. We also observed moderate variations both of selected PI-PLC enzymes within the cell and of expression of the corresponding PLC genes. In 143B cell line the transcription of PLCB1 decreased, of PLCG2 increased and of PLCE differed in a time-dependent manner. In Hs888, the expression of PLCB1 and of PLCD4 significantly increased, of PLCE moderately increased in a time dependent manner; the expression of PLCG2 was up-regulated. These observations indicate that Ezrin silencing affects the transcription of selected PLC genes, suggesting that Ezrin might influence the expression regulation of PI-PLC enzymes.

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.

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.

Pigmented villonodular synovitis of the shoulder associated with massive rotator cuff tear treated by arthroscopic synovectomy and debridement.

PURPOSE: Pigmented villonodular synovitis (PVNS) is a rare condition. Our purpose is to describe the largest series of patients with shoulder PVNS, massive irreparable rotator cuff tear, and glenohumeral osteoarthritis treated with arthroscopic debridement and synovectomy. METHODS: We treated 9 patients with PVNS of the shoulder, irreparable rotator cuff tear, and slight glenohumeral arthropathy (group I). Patients underwent arthroscopic synovectomy and debridement. Results [constant score (CS) and subjective shoulder value (SSV)] were compared to those obtained from a control group (group II) of 20 consecutive patients undergoing arthroscopic debridement for irreparable cuff tear associated with hemorrhagic synovitis with no or slight glenohumeral arthropathy. Histologic examination was obtained in all cases to obtain the correct diagnosis. RESULTS: The preoperative shoulder function in group I was reduced with respect to group II. Upon follow-up, CS and SSV were lower in group I. Preoperatively, the differences relating to the CS value and to each item of the score were always statistically significant; instead, at follow-up, significant differences emerged in the CS, ADL, and ROM. At follow-up, significant differences emerged between CS of group I and of group II without glenohumeral arthropathy. Differences using the SSV were always statistically significant. CONCLUSIONS: The poor functional outcome of patients affected by PVNS can be attributed to the coexistence of the irreparable cuff tear and to the glenohumeral arthropathy. All patients with PVNS had shoulder osteoarthritis; it cannot be simply attributed to natural history of massive irreparable cuff tears, but to the pigmented villonodular synovitis.

Lypopolysaccharide downregulates the expression of selected phospholipase C genes in cultured endothelial cells.

The signaling system of phosphoinositides (PI) is involved in a variety of cell and tissue functions, including membrane trafficking, ion channel activity, cell cycle, apoptosis, differentiation, and cell and tissue polarity. Recently, PI and related molecules, such as the phosphoinositide-specific phospholipases C (PI-PLCs), main players in PI signaling were supposed to be involved in inflammation. Besides the control of calcium levels, PI-PLCs contribute to the regulation of phosphatydil-inositol bisphosphate metabolism, crucial in cytoskeletal organization. The expression of PI-PLCs is strictly tissue specific and evidences suggest that it varies under different conditions, such as tumor progression or cell activation. In a previous study, we obtained a complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for endothelial cells. In the present study, we analyzed the mRNA concentration of PI-PLCs in lipopolysaccharide (LPS)-treated HUVEC by using the multiliquid bioanalyzer methodology after 3, 6, 24, 48, and 72 h from LPS administration. Marked differences in the expression of most PI-PLC codifying genes were evident.

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.

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.

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.