Evaluation of an electro-pneumatic device for artificial capillary pulse generation used in a prospective study in animals for surgical neck wound healing

The paper examines the development and testing of an electro-pneumatic device for wound healing therapy after surgery in the neck area. The device generates air pressure values in a miniaturized cuff using electronic circuitry to drive an electro-valve and air compressor. The device works in two distinct modes: continuous pressure mode and pulsating pressure mode. The pressure value setting can vary from 3 to 11 mmHg, and the pulsating pressure mode's operating frequency range is approximately 0.1 to 0.3 Hz. Laboratory measurements were conducted to evaluate the device's correct functioning in both continuous and pulsating pressure modes. A four-day prospective study with animals (n = 10) was also conducted to evaluate neck wound healing therapy using the electro-pneumatic device. Out of the twelve histological parameters analysed to reveal the differences between the experimental and control wounds, only one demonstrated a significant difference. Out of the ten animals treated with the device, three showed a significant difference in terms of benefit after therapy. We can therefore conclude that the device potentially improves the wound healing process in the neck area if the pre-set air pressure value does not exceed 8 mmHg.Web of Science9art. no. 983

Kit receptor tyrosine kinase dysregulations in feline splenic mast cell tumours

This study investigated Ki t receptor dysregulations (cytoplasmic immunohistochemical expression and/or c-KIT mutations) in cats a\ufb00ected with splenic mast cell tumours. Twenty-two cats were included. Median survival time was 780 days (range: 1\u20131219). An exclusive splenic involvement was signi\ufb01cantly (P = 0.042) associated with longer survival (807 versus 120 days). Eighteen tumours (85.7%) showed Kit cytoplasmic expression (Kit pattern 2, 3). Mutation analysis was successful in 20 cases. Fourteen missense mutations were detected in 13 out of 20 tumours (65%). Eleven (78.6%) were located in exon 8, and three (21.6%) in exon 9. No mutations were detected in exons 11 and 17. Seven mutations corresponded to the same internal tandem duplication in exon 8 (c.1245_1256dup). Although the association between Kit cytoplasmic expression and mutations was signi\ufb01cant, immunohistochemistry cannot be considered a surrogate marker for mutation analysis. No correlation was observed between c-Kit mutations and tumour di\ufb00erentiation, mitotic activity or survival

Red mark syndrome of trout (Oncorhynchus mykiss; Walbaum, 1792): Histopathological scoring and correlation with gross lesions

Red mark syndrome (RMS) is a skin disorder affecting rainbow trout (Oncorhynchus mykiss). The present work aimed to correlate the gross skin lesions affecting 46 fish sampled from farms surveyed for RMS with their microscopic features, identifying histological parameters that may be suggestive of disease progression. Skin lesions were grossly included in one of three categories (types I, II and III) according to the progressive degree of severity. Histological parameters and anti-proliferating cell nuclear antigen (PCNA) tissue immunoreactivity were semi-quantitatively assessed. In the dermis, PCNA-positive lymphocytes, fibroblasts and endothelial cells were indicative of active phlogosis. A significant increase in PCNA-immunoreactive lymphocytes, from gross type I to type III cases, was found only in the hypodermis. The histological parameters significantly associated with the gross lesion severity were progressive loss of the epithelium and scales, recruitment of inflammatory cells in the stratum compactum, loss of architecture of the stratum compactum, perivascular and perineural granulomatous inflammation and increase in lymphocyte infiltration of the muscular layer. In the type II and type III categories, inflammation in the hypodermis and muscle displayed a granulomatous pattern, reinforcing the hypothesis of an immunopathological mechanism. The morphological diagnosis of “deep chronic dermatitis associated to panniculitis and myositis, characterised by lympho-histiocytic and granulomatous reaction” is suggested

Evaluation of the histological parameters in usual interstitial pneumonia (idiopathic pulmonary fibrosis)

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a progressive interstitial pulmonary disease of unknown etiology. Since Hamman's and Rich's (1944) reports, many studies have tried to find a histological marker for the correlation between prognosis and response to therapy. However, there are many doubts regarding pathogenesis. In addition, it is generally accepted that response to therapy is related to the relative degree of cellularity and fibrosis. The purpose of this study is to describe the results of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, using a semi-quantitative method by independent evaluation of two pathologists, in 24 open lung biopsies with the diagnosis of idiopathic pulmonary fibrosis. Fourteen histological features were analyzed using the 0 to 5 scale for interstitial alterations and the 0 to 2 scale for the airway changes. There was significant interobserver agreement for all histological features with Kw (Kappa) variations between 0.47 and 0.92. There was significant disagreement only for septal inflammatory intensity analysis, suggesting that these features must be discussed by the pathologists. The semi-quantitative method assessment was effective.A fibrose pulmonar idiopática (alveolite fibrosante criptogênica) é uma doença pulmonar intersticial progressiva de etiologia desconhecida, morfologicamente reconhecida como pneumonia intersticial usual. Desde a publicação de Hamman e Rich (1944) até os dias atuais, uma das grandes preocupações foi a tentativa de encontrar um marcador histológico para correlacionar com prognóstico e resposta terapêutica. A busca desta situação não tem sido muito alentadora, pois existem vários pontos duvidosos na patogênese desta doença. Admite-se que a resposta terapêutica desta entidade se relaciona com a celularidade e fibrose presentes no tecido. A proposta deste estudo é descrever os resultados de método semiquantitativo segundo a avaliação independente de dois patologistas, das alterações exsudativo-inflamatórias, reparativo-fibróticas e de vias aéreas, em 24 pacientes com diagnóstico de fibrose pulmonar idiopática, submetidos à biópsia a céu aberto. Foram analisados 14 parâmetros histológicos segundo escala de 0 a 5 para as alterações intersticiais e de 0 a 2 para o comprometimento de vias aéreas e de espaços aéreos. Da análise independente realizada pelos dois observadores constatou-se concordância significante em todas as variáveis histológicas com Kw (teste de Kappa) indo de 0,47 a 0,92. Apenas na análise da intensidade da inflamação septal as discordâncias também foram significantes, sugerindo que para este parâmetro a percentagem de comprometimento tecidual deve ser previamente discutida entre os observadores. O método utilizado demonstrou ser rápido e eficiente.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUNIFESP, EPM, Depto. de PatologiaSciEL

Preliminary investigation of the effects of long-term dietary intake of genistein and daidzein on hepatic histopathology and biochemistry in domestic cats (Felis catus)

Dietary isoflavones have been hypothesised to play a role in hepatic veno-occlusive disease in captive exotic felids, although empirical evidence is lacking. This study aimed to investigate the effect of long-term (>1 year) dietary genistein and daidzein exposure on the hepatic biochemistry and histology of domestic cats. Individual cats were assessed for hepatic enzyme and bile acid production before and after the removal of isoflavones from their diet in the treatment group (n=4), and at the same times in unexposed control animals (n=7). No significant differences were detectable in hepatic biochemistry between treatment and control groups, and all serum values were within the normal reference ranges for domestic cats. Additionally, treatment animals demonstrated slightly greater areas of fibrosis surrounding hepatic venules than control animals, but this difference was not statistically significant. On the basis of the results presented, dietary isoflavones, at the current dose and duration of exposure do not appear to modulate hepatic enzyme production or histological parameters

Histological subclassification of cirrhosis based on histological-haemodynamic correlation

Background: Determining a relationship between specific histological parameters in cirrhosis and hepatic venous pressure gradient can be used to subclassify cirrhosis. Aim: To determine the relationship between hepatic venous pressure gradient and specific histological parameters in cirrhosis. Methods: Forty-seven patients (mean age: 46.2 ± 13.6 years; 36 male) with biopsy-proven cirrhosis and hepatic venous pressure gradient measurements within 1 month of biopsy were studied. The following histological parameters were scored semiquantitatively: nodule size, loss of portal tracts and central veins, portal inflammation, periportal inflammation, bile duct proliferation, lobular inflammation, ballooning, fatty change, cholestasis and septal thickness. Results: On multiple ordinal regression analysis, small nodule size (odds ratio: 21.0; 95% confidence interval: 2.1-208.2, P = 0.009) and thick septa (OR: 42.6; CI: 2.3-783.7, P = 0.011) were significantly associated with the presence of clinically significant portal hypertension. A score was assigned to each of the two parameters (nodule size: large = 1, medium = 2, small = 3 and septal thickness: thin = 1, medium = 2, thick = 3). Two subcategories were devised based on the composite score: category A (n = 12): score 1-3 and category B (n = 35): score 4-6. On ordinal regression, subcategory B (OR: 15.5; CI: 3.3-74.2, P = 0.001) was significantly associated with clinically significant portal hypertension. Conclusion: Small nodularity and thick septa are independent predictors of the presence of clinically significant portal hypertension

Analytical and numerical analyses of the micromechanics of soft fibrous connective tissues

State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting, close form expressions, are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method these predictions are compared with corresponding 3-D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Reduced expression of chemerin in visceral adipose tissue associates with hepatic steatosis in patients with obesity

Objective: This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance. Methods: Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects. Expression in VAT was measured using real-time PCR and histopathological grading was scored using the NAFLD activity score (NAS). Results: When NAFLD patients were subdivided into groups with simple steatosis, borderline nonalcoholic steatohepatitis (NASH), and NASH, adiponectin serum levels and omentin expression were lower in NASH versus simple steatosis patients. Serum adiponectin was generally lower with higher histopathological grading. Chemerin VAT expression was negatively associated with NAS (r = -0.331, P = 0.022) and steatosis score (r = -0.335, P = 0.020), independent of age, BMI, and HOMA-IR. In addition, adjusting for chemerin VAT expression in a multivariate model explained part of the association between NAS and HOMA-IR. Conclusions: These findings suggest that lower VAT expression of chemerin in patients with obesity may be involved in the pathophysiology of hepatic steatosis, potentially by modulating the link between insulin resistance and NAFLD

A urinary Common Rejection Module (uCRM) score for non-invasive kidney transplant monitoring.

A Common Rejection Module (CRM) consisting of 11 genes expressed in allograft biopsies was previously reported to serve as a biomarker for acute rejection (AR), correlate with the extent of graft injury, and predict future allograft damage. We investigated the use of this gene panel on the urine cell pellet of kidney transplant patients. Urinary cell sediments collected from patients with biopsy-confirmed acute rejection, borderline AR (bAR), BK virus nephropathy (BKVN), and stable kidney grafts with normal protocol biopsies (STA) were analyzed for expression of these 11 genes using quantitative polymerase chain reaction (qPCR). We assessed these 11 CRM genes for their abundance, autocorrelation, and individual expression levels. Expression of 10/11 genes were elevated in AR when compared to STA. Psmb9 and Cxcl10could classify AR versus STA as accurately as the 11-gene model (sensitivity = 93.6%, specificity = 97.6%). A uCRM score, based on the geometric mean of the expression levels, could distinguish AR from STA with high accuracy (AUC = 0.9886) and correlated specifically with histologic measures of tubulitis and interstitial inflammation rather than tubular atrophy, glomerulosclerosis, intimal proliferation, tubular vacuolization or acute glomerulitis. This urine gene expression-based score may enable the non-invasive and quantitative monitoring of AR