Korelacija ekspresije TGF-β i MMP2 između adenokarcinoma prostate i okolnog nezahvaćenog parenhima

In prostate adenocarcinoma, both tumorous stroma and epithelium have important role in tumor progression. Transforming growth factor beta (TGF- β) is a promotor in advanced stages of prostate cancer. Matrix Metalloproteinase 2 (MMP2), the endopeptidase that degrades extracellular matrix is considered to be overexpressed in prostatic carcinoma related to its growth and aggressiveness. Therefore, the aim was to analyze the expression of proteins TGF- β and MMP2 between both epithelium and stroma of prostatic adenocarcinoma and adjacent unaffected parenchyma. The intensity of TGF- β and MMP2 expression in epithelium, tumorous stroma and adjacent unaffected parenchyma was analyzed in 62 specimens of prostatic adenocarcinoma by microarray-based immunohistochemistry. TGF- β was more expressed in tumorous than in prostate stroma (p =0.000), while no statistical significance in case of MMP2 (p = 0.097) was found. MMP2 was more expressed in tumorous than in prostate epithelium (p =0.000), while no statistical significance in case of TGF- β (p = 0.096) was observed. The study results indicate that both tumorous stroma and epithelium have a role in tumor progression and support potential role of TGF- β and MMP2 in prostatic adenocarcinoma progression.U progresiji karcinoma prostate tumorska stroma i epitel imaju važnu ulogu. Beta transformirajući faktor rasta (TGF- β) djeluje kao promotor u uznapredovalom raku prostate, a matriks metaloproteinaza 2 (MMP2) kao endopeptidaza koja razgrađuje izvanstanični matriks te je njezina aktivnost pojačano izražena te povezana s rastom i agresivnošću ovog tumora. Stoga je cilj ovog istraživanja bio analizirati izraženost TGF- β u MMP2 između epitela i strome karcinoma prostate te okolnog tumorom nezahvaćenog parenhima prostate. Intenzitet izraženosti TGF- β i MMP2 u tumorskom epitelu i stromi te okolnom nezahvaćenom parenhimu je analiziran u 62 pacijenta s adenokarcinomom prostate metodom imunohistokemijske analize na uzorcima microarray-a. TGF- β je bio izraženiji u tumorskoj nego u ne- tumorskoj stromi (p =0.000), dok u slučaju izraženosti MMP2 nije pokazana statistička značajnost (p = 0.097). MMP2 je bila izraženija u tumorskom epitelu u odnosu na ne- tumorski epitel (p =0.000), dok statistička značajnost u slučaju izraženosti TGF- β nije pokazana (p = 0.096). Rezultati ovog istraživanja pokazuju da i tumorski epitel i stroma imaju ulogu u progresiji tumora i ukazuju na potencijalnu ulogu TGF- β i MMP2 u progresiji adenokarcinoma prostate

Prolonged acute kidney injury exacerbates lung inflammation at 7 days post‐acute kidney injury

Patients with acute kidney injury (AKI) have increased mortality; data suggest that the duration, not just severity, of AKI predicts increased mortality. Animal models suggest that AKI is a multisystem disease that deleteriously affects the lungs, heart, brain, intestine, and liver; notably, these effects have only been examined within 48 h, and longer term effects are unknown. In this study, we examined the longer term systemic effects of AKI, with a focus on lung injury. Mice were studied 7 days after an episode of ischemic AKI (22 min of renal pedicle clamping and then reperfusion) and numerous derangements were present including (1) lung inflammation; (2) increased serum proinflammatory cytokines; (3) liver injury; and (4) increased muscle catabolism. Since fluid overload may cause respiratory complications post-AKI and fluid management is a critical component of post-AKI care, we investigated various fluid administration strategies in the development of lung inflammation post-AKI. Four different fluid strategies were tested - 100, 500, 1000, or 2000 μL of saline administered subcutaneously daily for 7 days. Interestingly, at 7 days post-AKI, the 1000 and 2000 μL fluid groups had less severe AKI and less severe lung inflammation versus the 100 and 500 μL groups. In summary, our data demonstrate that appropriate fluid management after an episode of ischemic AKI led to both (1) faster recovery of kidney function and (2) significantly reduced lung inflammation, consistent with the notion that interventions to shorten AKI duration have the potential to reduce complications and improve patient outcomes

The role of CD4+FOXP3+ I CD4+TH17+ lymphocytes in borderline acute cellular rejection of renal allografts

Granično akutno celularno odbacivanje bubrežnog presatka (granično ACO) je karakterizirano histološkim promjenama koje upućuju na akutno celularno odbacivanje, ali ne zadovoljavaju sve kriterije potrebne za postavljanje definitivne dijagnoze akutnog celularnog odbacivanja. Pokušali smo odrediti može li postotak limfocita CD4+Foxp3+ i CD4+Th17+ u upalnom infiltratu bubrežnog presatka s histološkim karakteristikama graničnog ACO pomoći u određivanju radi li se o reakciji akutnog odbacivanja presatka ili fiziološkoj prilagodbi organizma na donirani organ. Uz to smo pokušali utvrditi povezanost limfocita CD4+Foxp3+ i CD4+Th17+ s nastajanjem akutnih i kroničnih promjena u transplantatu bubrega. Zaključeno je da limfociti CD4+Th17+ pojačavaju akutne upalne promjene i vjerojatno sudjeluju u njihovom nastanku dok limfociti CD4+Foxp3+ u bubrežnom presatku s graničnim ACO nisu povezani s histološkim i kliničkim pokazateljima reakcije odbacivanja. Zaključeno je i da prisutnost limfocita CD4+Th17+ u graničnom ACO može poslužiti za definiranje stvarnog ACO u pacijenata s histološkim graničnim ACO tako što veći broj označava reakciju odbacivanja.Borderline acute cellular rejection of renal allograft (borderline ACR) is considered when histological changes in renal allograft tissue are suspicious for rejection, but do not have enough criteria for making a diagnosis of acute cellular rejection. We wanted to define if CD4+Foxp3+ and CD4+Th17+ lymphocytes in renal allograft tissue with borderline ACR can determine if the reaction is indeed acute rejection or is it just physiological conditioning of the body to new organ. Also, we wanted to explore if these lymphocytes are involved in arising of acute and chronic changes in renal allograft. Based on the results we concluded that CD4+Th17+ lymphocytes increase acute changes and probably have a role in their evolving while the number of CD4+Foxp3+ lymphocytes does not correlate with rejection in borderline ACR, but the number of CD4+Th17+ lymphocytes in renal allograft tissue with borderline ACR can determine if the reaction is indeed acute rejection

Enfermedad mediada por autoanticuerpos IgA anti-membrana basal glomerular

Anti-glomerular basement membrane disease (anti-GBM) is a rare disease usually mediated by IgG autoantibodies. It usually presents as rapidly progressive glomerulonephritis, often accompanied by pulmonary hemorrhage.1 The hallmark of anti-GBM disease are the blood circulating and tissue-bound autoantibodies that target antigenic sites within the glomerular basement membrane (GBM) and sometimes alveolar basement membranes. We present a rare case of anti-GBM disease mediated by IgA autoantibody. A 65-year-old-man presented with gross haematuria and nephrotic range proteinuria and was admitted to the hospital

Extremely Well-differentiated Gastric Adenocarcinoma Arising in Pylorus with Minor Diffuse Adenocarcinoma Component

Gastric adenocarcinoma is generally a disease of the middleaged and elderly with a peak incidence in patients over 65 years. The highest rates in the world are reported in Eastern Asia. Based on Lauren classification, gastric adenocarcinomas have been classified into two types, intestinal and diffuse types. A subset of gastric adenocarcinomas has been described under the name of Bextremely well-differentiated gastric adenocarcinoma (EWDGA). It is defined as a neoplastic lesion composed of highly differentiated neoplastic epithelium which mimics the normal gastric mucosa or intestinal metaplastic mucosa with mild nuclear atypia. It is considered a low-grade carcinoma accounting for around 0.1 % of all gastric tumours. We report a case of EWDGA that differs from previously described cases in order that there was a presence of a minor intramucosal diffuse adenocarcinoma component, which has not been reported up to date in patients with EWDGA

IgM as a novel predictor of disease progression in secondary focal segmental glomerulosclerosis

AIM: To determine the role of immunoglobulin M (IgM) deposits in clinical manifestations, disease outcome, and treatment response of idiopathic and secondary focal segmental glomerulosclerosis (FSGS). ----- METHODS: Kidney biopsy specimens of 171 patients diagnosed with FSGS (primary and secondary) and 50 control patients were retrospectively included in the study. For each patient, clinical and outcome data were obtained and compared to morphological parameters, including immunofluorescence analysis of mesangial IgM and complement 3 (C3) deposits analyzed on kidney biopsy samples. ----- RESULTS: There were significant positive correlations between IgM and C3 deposition in secondary FSGS (P<0.001) and between IgM and mesangial deposits detected by electron microscopy in secondary FSGS (P=0.015), which indicated that higher IgM deposition correlated with higher C3 deposition and mesangial deposits only in secondary FSGS. Patients with secondary FSGS and the deposition of IgM showed inferior renal outcomes at earlier time points in comparison with patients with negative IgM expression (P=0.022). ----- CONCLUSIONS: We detected a positive correlation between IgM and C3 in secondary FSGS. The association between IgM deposition and worse renal outcome in secondary FSGS indicates that IgM may play a role in the progression of this disease