Grade Group accuracy is improved by extensive prostate biopsy sampling, but unrelated to prostatectomy specimen sampling or use of immunohistochemistry.

Assessing the accurate Grade Group of a prostate needle biopsy specimen is essential for choosing the adequate therapeutic modality for prostate cancer patients. However, it is well-known that biopsy Grade Group tends to up- or downgrade significantly at radical prostatectomy. We aimed to investigate the correlation between accuracy and biopsy core number, performed immunohistochemical staining (IHC) or prostatectomy specimen sampling, with the latest also being correlated with higher detection rates of adverse pathological features, e.g., positive surgical margins, higher pathological stage or presence of perineural invasion (PnI status). The study cohort consisted of 315 consecutive patients diagnosed with prostate adenocarcinoma via transrectal ultrasound-guided needle biopsy who later underwent radical prostatectomy. We grouped and compared patients based on Grade Group accuracy, presence of IHC on biopsy, margin status, pathological stage, and PnI status. Inter-observer reproducibility was also calculated. Statistical analyzes included ANOVA, Tukey's multiple comparisons post hoc test, Chi-squared test, and Fleiss kappa statistics. Undergraded cases harboured a significantly lower number of biopsy cores (p < 0.05), than accurately graded cases. Using IHC did not affect grading accuracy significantly, nor did the number of slides from prostatectomy specimens. The mean number of slides was virtually identical when margin status, pathological stage and PnI status of prostatectomy specimens were compared. Inter-observer reproducibility at our institute was calculated as fair (overall kappa = 0.29). Grade Group accuracy is significantly improved by obtaining more cores at biopsy but is unrelated to performed IHC. The extent of sampling prostatectomy specimens, however, did not affect accuracy and failed to significantly improve detection of adverse pathological features.

Tubular basement membrane amyloid deposition: is it an indicator of renal progression in light chain amyloidosis?

In light chain amyloidosis (LA), the massive glomerular and vascular amyloid deposition leading to interstitial fibrosis/tubular atrophy (IFTA) is thought to be responsible for renal failure. The amyloid deposition in the interstitium and the tubular basement membrane (TBM) has received less attention in the study of LA. We, therefore, collected clinical and laboratory data on patients diagnosed with LA in our Nephrology Department and studied amyloid deposition in the TBM. Twelve LA patients were diagnosed by renal biopsy during a seven-year period. In 4 of the 12, amyloid deposition could also be detected in the TBM. In our first case of a patient with diabetes mellitus, non-amyloid fibrils resembling 'diabetic fibrillosis' were also seen by electron microscopy. Despite the double damage, IFTA was negligible, blood vessels were unaffected, and the glomerular deposition was segmental. In the other three cases, significant (>50%) IFTA and a severely reduced estimated glomerular filtration rate were already detected at the time of diagnosis and amyloid deposition was also observed in the blood vessels. These findings indicate the importance of TBM amyloid deposition in the progression of renal disease. This may represent a late-stage presentation of the disease with a heavy LC burden.

Case report: Metastatic pancreatic neuroendocrine tumour associated with portal vein thrombosis; successful management with subsequent pregnancies.

Background: Splanchnic vein thrombosis due to co-existing metastatic pancreatic neuroendocrine tumour (pNET) and JAK2V617F mutation is a rare condition. Case report: Here we present a case of a young woman with complete remission of a non-functioning grade 2 pNET with unresectable liver metastases, coexisting with JAK2V617F mutation. Splenectomy and distal pancreatectomy were performed. Neither surgical removal, nor radiofrequency ablation of the liver metastases was possible. Therefore, somatostatin analogue (SSA) and enoxaparine were started. Peptide receptor radionuclide therapy (PRRT) was given in 3 cycles 6-8 weeks apart. Genetic testing revealed no multiple endocrine neoplasia type 1 (MEN-1) gene mutations. After shared decision making with the patient, she gave birth to two healthy children, currently 2 and 4 years old. On pregnancy confirmation, SSA treatment was interrupted and resumed after each delivery. Ten years after the diagnosis of pNET, no tumour is detectable by MRI or somatostatin receptor scintigraphy. PRRT followed by continuous SSA therapy, interrupted only during pregnancies, resulted in complete remission and enabled the patient to complete two successful pregnancies.

An Ultra-Rare Manifestation of an X-Linked Recessive Disorder: Duchenne Muscular Dystrophy in a Female Patient.

Duchenne muscular dystrophy (DMD) is the most common inherited muscle dystrophy. Patients are characterized by muscle weakness, gross motor delay, and elevated serum creatinine kinase (CK) levels. The disease is caused by mutations in the DMD gene located on the X chromosome. Due to the X-linked recessive inheritance pattern, DMD most commonly affects males, who are generally diagnosed between the age of 3-5 years. Here we present an ultra-rare manifestation of DMD in a female patient. Cytogenetic examination showed that she has a t(X;10)(p21.1;p12.1) translocation, which turned out to affect the DMD gene with one of the breakpoints located in exon 54 (detected by genome sequencing). The X-inactivation test revealed skewed X-inactivation (ratio 99:1). Muscle histology and dystrophin immunohistochemistry showed severe dystrophic changes and highly reduced dystrophin expression, respectively. These results, in accordance with the clinical picture and a highly elevated serum CK, led to the diagnosis of DMD. In conclusion, although in very rare cases, DMD can manifest in female patients as well. In this case, a balanced X-autosome reciprocal translocation disrupts the DMD gene and skewed X-inactivation leads to the manifestation of the DMD phenotype.

Investigation of Circulating MicroRNA Levels in Antibody-Mediated Rejection After Kidney Transplantation.

BACKGROUND: One of the most important possible complications determining long-term graft survival after kidney transplant is antibody-mediated rejection (ABMR). The criterion standard approach to recognize ABMR is currently the kidney biopsy with histopathologic analysis. However, this test has limitations because of difficulties in timing of sampling, the evaluability of histology because of the questionable representativeness of specimens, and the limited number of this intervention. Hence, new reliable, noninvasive biomarkers are required to detect the development of ABMR in time. METHODS: In this study, we analyzed the clinical data of 45 kidney transplant patients (mean age of 44.51 years, 20 male and 25 female subjects). These participants were recruited into 5 subcohorts based on their clinical status, histologic findings, and level of donor-specific anti-HLA antibodies. Circulating microRNAs (miR-21, miR-181b, miR-146a, miR-223, miR-155, miR-150) in plasma samples were quantified by quantitative polymerase chain reaction and their levels were correlated with the clinical characteristics in different subgroups. RESULTS: The relative expression of plasma miR-155 (P = .0003), miR-223 (P = .0316), and miR-21 (P = .0147) were significantly higher in patients who had subsequent histology-approved ABMR with donor-specific anti-HLA antibody positivity (n = 10) than in the "triple negative" group (n = 21), and miR-155 showed the highest sensitivity (90%) and specificity (81%) to indicate ABMR development based on receiver operating characteristic analysis. CONCLUSIONS: According to our preliminary data, plasma miR-155, miR-21, and miR-223 can indicate the development of ABMR after kidney transplant in correlation with classic clinical parameters. However, future studies with larger number of participants are necessary to further evaluate the diagnostic properties of blood miRNAs in prediction of this life-threatening condition.

Analysis of pathological and biological features of small renal masses based on the tumor size / Kis méretu vesedaganatok patológiai és biológiai jellemzoinek elemzése a tumorméret alapján.

Összefoglaló. Bevezetés: A kis méretu vesedaganatok között lényegesen gyakoribbak a benignus elváltozások, és a kis malignus tumorok biológiai tulajdonságai is kedvezobbek, mint a nagyobb daganatokéi. Célkituzés: Szerzok a kis méretu vesetumorok tulajdonságait vizsgáltuk különbözo alcsoportokban. Módszer: 2000. január 1. és 2015. január 1. között 1272 beteg esetén végeztünk mutétet vesedaganat miatt. Közülük 496 betegnek volt kis méretu vesetumora. A betegek átlagéletkora 59 ± 12 év volt. A betegeket a tumorméret alapján három csoportba osztottuk. Az 1. csoportban a daganat mérete ≤4 cm, a 2. csoportban ≤3 cm és a 3. csoportban ≤2 cm volt. Eredmények: Az eltávolított daganat nagysága átlagosan 29 ± 8 mm volt. A szövettan 418 esetben (84%) malignus, míg 78 alkalommal (16%) benignus elváltozást mutatott. A 2 cm-nél kisebb daganatoknál malignitás csak az esetek 73,2%-ában fordult elo. A malignus és a benignus tumorok méretében szignifikáns eltérés volt (p = 0,008). Rosszul differenciált daganat - grade 3. és 4. - az esetek 10,8%-ában, 14,4%-ában, illetve 20,7%-ában volt jelen, amikor a tumorméret kisebb mint 2 cm, 2,1-3 cm, illetve 3,1-4,0 cm volt. A vesecarcinomáknál az átlagosan 10 éves utánkövetési ido alatt progresszió az esetek 5,5%-ában fordult elo. Következtetés: A kis méretu vesetumor az összes vesedaganat 39%-át tette ki. Ezek nagy része malignus volt, és benignus elváltozás az esetek 16%-ában fordult elo. A malignitás elofordulása a 2 cm-nél kisebb tumoroknál volt a legalacsonyabb. A tumorméret szoros összefüggést mutatott a malignitás gyakoriságával és a daganat differenciáltságával. A kedvezo patológiai és biológiai eredmények alapján a 2 cm alatti daganatoknál felmerül annak lehetosége, hogy esetükben az aktív követés vagy minimálisan invazív kezelés alkalmazása kerüljön elotérbe. Orv Hetil. 2021; 162(42): 1693-1697. INTRODUCTION: The incidence of benign lesions is more common in small renal masses (SRMs) and biological behavior of small malignancies is better compared to larger ones. OBJECTIVE: The authors measured the characteristics of SRMs in different subgroups. METHOD: From January 1, 2000 to January 1, 2015, 1272 patients underwent surgery for renal tumors. In 496 of the 1272 cases, the patients had SRMs. The mean age of the patients was 59 ± 12 years. Based on the sizes, the SRMs were divided into three groups. The sizes of the renal tumors were ≤4 cm in Group 1, ≤3 cm in Group 2 and ≤2 cm in Group 3. RESULTS: The mean diameter of the removed SRMs was 29 ± 8 mm. Histology confirmed renal cell carcinoma in 418 cases (84%), while benign tumor was present in 78 patients (16%). However, with the tumor size ≤2 cm, malignancy was detected in 73.2% of the cases. There was a significant difference in the sizes of the malignant and the benign masses (p = 0.008). Grade 3 or 4 tumors were present in 10.8%, 14.4% and 20.7% when the tumor size was ≤2 cm, 2.1 to 3 cm, and 3.1 to 4 cm in diameter, respectively. During the mean 10-year follow-up period, tumor progression was detected only in 5.5% of malignancies. CONCLUSION: In 39% of all cases, the patients had SRMs. The majority of SRMs were malignant, and benign lesion occurred only in 16% of the cases. The incidence of malignant tumors was the lowest when the size of SRMs was ≤2 cm. The size of the tumor was highly associated with probability of malignancy and tumor grading. Based on the favorable pathological and biological results in tumors below 2 cm, active surveillance or minimally invasive treatment could be the preferred management. Orv Hetil. 2021; 162(42): 1693-1697.

Management of antibody-mediated rejection after kidney transplantation in our clinical practice / Az antitestmediált rejekció diagnosztikája és kezelése gyakorlatunkban.

Összefoglaló. Bevezetés: Az antitest közvetítette kilökodés a graftvesztés gyakori oka a vesetranszplantáltak körében. Célkituzés: Célul tuztük ki, hogy ismertetjük a centrumunkban biopsziával igazolt humorális kilökodéssel rendelkezo betegeknek a kezelésre (standard kezelés: plazmaferézis, immunglobulin, rituximab) adott válaszát, valamint hogy vizsgáljuk a proteinuria grafttúlélésre kifejtett hatását és azt, hogy ezt a DSA-tól függetlenül teszi-e. Vizsgáltuk az eGFR-, a DSA-MFI-értéknek az antirejekciós terápia hatására bekövetkezo változásait is. Módszer: 85 beteg retrospektív analízisét végeztük el. A szövettani elemzésben a Banff-klasszifikációt vettük alapul. A csoportok összehasonlításához kategorikus változók esetén a Fisher-féle egzakt próbát, folyamatos változók esetén a Kruskal-Wallis-próbát használtuk. Eredmények: A biopsziával igazolt humorális rejekciós csoportba (ABMR-csoport) 19, a DSA-pozitív csoportba 14, a DSA-negatív csoportba 52 beteget választottunk be. A DSA-érték az ABMR-csoportban 61,16%-kal csökkent, a DSA-pozitív csoportban 42,86%-kal redukálódott (Fisher-féle egzakt: p = 0,1). Az ABMR-csoportban 9 betegnek a jelentos, 4-nek a nephroticus mértéku proteinuriája csökkentheto volt (az ABMR-csoport 68%-a). A legjobb grafttúlélés a legalacsonyabb fehérjeürítésnél adódott. Az antirejekciós terápiát követoen készült biopsziákban: a glomerulitis, az interstitialis gyulladás, az arteritis mértéke csökkent az antihumorális kezelés hatására, azonban krónikus elváltozások jelentek meg. Következtetés: Az ABMR-csoportban az antirejekciós terápiát követoen a fehérjeürítés monitorizálása javasolt, hiszen becsülheto vele a grafttúlélés. Orv Hetil. 2021; 162(26): 1029-1037. INTRODUCTION: Antibody-mediated rejection is a common cause of graft loss among kidney transplant recipients. OBJECTIVE: We aimed to describe the response of patients with biopsy-proven humoral rejection to treatment (standard treatment: plasmapheresis, immunoglobulin, rituximab) in our center. We also analyzed the effect of proteinuria on graft survival and whether this effect is independent of donor-specific antibodies (DSAs). Changes of eGFR and level of DSA following rejection treatment were examined. METHOD: In this study, laboratory data of 85 patients were analysed. Histological analysis was based on the Banff classification. Fisher's exact test was used for statistical analysis, and Kruskal-Wallis test was used to compare patient groups per variable. RESULTS: Data from 85 patients were processed retrospectively. 19 patients were selected for the biopsy-confirmed humoral rejection group (ABMR group), 14 for the DSA-positive group, and 52 for the DSA-negative group. DSA titer decreased by 61.16% in the ABMR group after treatment and by 42.86% in the DSA-positive group (Fisher's exact test: p = 0.1). In the ABMR group, significant nephrotic proteinuria in 4 patients and severe proteinuria in 9 patients were reduced (68% of ABMR group). The patients with the lowest protein excretion had the best graft survival. In biopsies performed after antirejection therapy, the extent of glomerulitis, interstitial inflammation, arteritis decreased with antihumoral treatment, but chronic lesions appeared. CONCLUSION: Following treatment of biopsy-proven ABMR, reduction of proteinuria predicts graft survival and should be monitored as an important factor-predicting prognosis. Orv Hetil. 2021; 162(26): 1029-1037.

Ibrutinib-induced acute kidney injury via interstitial nephritis.

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.

Which remote ischemic preconditioning protocol is favorable in renal ischemia-reperfusion injury in the rat?

BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n = 7) or 24 hour (RIPC-24 group, n = 6) prior to the I/R. Hemodynamic, hematological parameters and organs' surface microcirculation were measured. RESULTS: Control and I/R group had the highest heart rate (p < 0.05 vs base), while the lowest mean arterial pressure (p < 0.05 vs RIPC-1) were found in the RIPC-24 group. The highest microcirculation values were measured in the I/R group (liver: p < 0.05 vs Control). The leukocyte count increased in I/R group (base: p < 0.05 vs Control), also this group's histological score was the highest (p < 0.05 vs Control). The RIPC-24 group had a significantly lower score than the RIPC-1 (p = 0.0025 vs RIPC-1). CONCLUSION: Renal I/R caused significant functional and morphological, also in the RIPC groups. According to the histological examination the delayed-effect RIPC method was more effective.

Microrheology, microcirculation and structural compensatory mechanisms of a chronic kidney disease rat model. A preliminary study.

BACKGROUND: Chronic kidney disease (CKD) models are known to study pathophysiology and various treatment methods. Renal dysfunction could influence erythrocytes through several pathways. However, hemorheological and microcirculatory relation of CKD models are not completely studied yet. OBJECTIVE: To evaluate erythrocyte micro-rheology, microcirculatory and structural compensatory mechanisms in a rat model of CKD. METHODS: Female Sprague-Dawley rats were subjected to nephrectomy group (NG, n = 6) or sham-operated group (SG, n = 6). NG rats were subjected to 5/6 nephrectomy in two stages. In SG no intervention was made on kidneys. Hemorheological and hematological measurements were carried out after each stage, and 5 weeks after the last operation. Histological and microcirculatory studies were done on the remaining kidney and compared with sham rats. RESULTS: Serum creatinine increased in NG (p = 0.008), accompanied with decrease of red blood cell count (p = 0.028) and hemoglobin (p = 0.015). Erythrocyte aggregation parameters slightly increased in NG, while the elongation index didn't show significant changes. Microcirculation was intact in the remnant kidney of NG. However, in comparison with SG, the diameter of glomeruli increased significantly (p < 0.01). CONCLUSIONS: Erythrocyte mass was influenced more than micro-rheological properties in this model. The main compensation mechanism was rather structural than at microcirculatory level.

N,N-dimethyltryptamine Prevents Renal Ischemia-Reperfusion Injury in a Rat Model.

BACKGROUND: Ischemia reperfusion (I/R) injury remains one of the most challenging fields of organ transplantation. It is highly associated with the use of expanded criteria donors that might conclude to delayed graft function or early or late graft failure. OBJECTIVE: To investigate the metabolic, microcirculatory parameters, and histologic changes under the effect of N,N-dimethyltryptamine (DMT) in a renal I/R model in rats. METHOD: In 26 anesthetized rats both kidneys were exposed. In the control group (n = 6) no other intervention happened. In 20 other animals, the right renal vessels were ligated, and after 60 minutes the right kidney was removed. The left renal vessels were clamped for 60 minutes then released, followed by 120 minutes of reperfusion. In the I/R group (n = 10), there was no additive treatment, while in I/R + DMT group (n = 10) DMT was administered 15 minutes before ischemia. Blood samples were taken, laser Doppler measurement was performed, and both kidneys were evaluated histologically. RESULTS: Microcirculation (blood flux units [BFU]) diminished in all groups, but remarkably so in the I/R + DMT group. This group compensated better after the 30th minute of reperfusion. The control and I/R + DMT groups had similar BFUs after 120 minutes of reperfusion, but in the I/R group BFU was higher. Tubular necrosis developed in the I/R and I/R + DMT groups too; it was moderated under DMT effect, and severe without. Histologic injuries were less in I/R + DMT Group compared to non-treated animals. CONCLUSION: Histologic changes characteristic to I/R injuries were reversible and microcirculation recovered at the end of 120 minutes reperfusion under the administration of DMT. DMT can be used for renoprotection in kidney transplantation.

[Antibody-mediated rejection: challenge of the treatment in kidney transplantated patients]. / Antitestmediált rejekció: kihívás a veseátültetett betegek kezelésében.

Antibody-mediated rejection (ABMR) is one of the factors affecting the long-term graft survival after kidney transplantation (KT). Two kidney transplant centres (University of Debrecen and University of Pécs) followed up their data of cadaveric KTs that had been performed between 2013 and 2017, and reviewed the literature. There were 454 KTs in the mentioned period, 18 cases (4%) were recognised as ABMRs. Biopsy has been performed in all cases. 22% were primary, and 78% retransplanted patients. The average age was 51.2 ± 6 years. ABMR occurred 15.4 ± 22.1 months after KT. Histology showed C4d positivity in 39% of the cases. The treatment was steroid bolus + intravenous immunoglobulin (IVIG) + plasma exchange (PE) in 16 cases, rituximab was additionally given in 5 cases. 47.4% of the patients are alive with a functioning graft, four (21%) died, and 31% of the patients had a graft loss due to ABMR. ABMR is a dangerous complication after KT. Diagnostic criteria has been unclear for years. Gold standard is the histology, however, accelerated ABMR may occur even in C4d negative cases. The exposed group includes young, retransplanted patients, having a preformed donor-specific antibody (DSA), and receiving a graft from an EC donor. The occurrence of de novo DSA and the kinetics of mean fluorescence intensity (MFI) of existing ones can be a signal for the risk of an ABMR. The effectiveness of rituximab is not proven, there is a lack of long-term controlled trials for new drugs. Our results of over 40% recovery is an extensively good result. Orv Hetil. 2018; 159(46): 1913-1929.

Carotid-Jugular Fistula Model to Study Systemic Effects and Fistula-Related Microcirculatory Changes.

BACKGROUND: Arteriovenous fistulae impair the distal circulation, but their effects at the microcirculatory level are not well understood. This study presents the carotid-jugular fistula (CJF) as a model to evaluate fistula-related microcirculatory and systemic changes. MATERIALS AND METHODS: Female Wistar rats were anesthetized and divided into a fistula group (FG, n = 10) and a sham group (SG, n = 6). End-to-end anastomosis was performed between the right carotid artery and the jugular vein in the FG. The hemodynamic status was followed for 6 weeks. On the sixth postoperative week, liver and kidney microcirculation was measured using laser Doppler; then microcirculatory changes were assessed after occlusion of the carotid artery. At the end of the experiment, histological samples were taken and the weights of the organs were measured. RESULTS: The heart rate and systolic blood pressure decreased significantly due to the CJF. Laser Doppler showed a reduction in liver blood flow units (BFU) in the FG in comparison with the SG (p = 0.01), and they increased (p < 0.01) after occlusion of the fistula. Kidney BFU showed slight changes only. The comparative morphological study revealed significant increases in heart weight (p < 0.001) and left ventricular hypertrophy (p = 0.008) in the FG. CONCLUSION: Beside hemodynamic and morphologic changes, a CJF causes a deterioration in the microcirculation of the liver rather than of the kidney, but occlusion of the CJF immediately reverses these changes.

Is the early or delayed remote ischemic preconditioning the more effective from a microcirculatory and histological point of view in a rat model of partial liver ischemia-reperfusion?1.

PURPOSE: To compare early- and late-effect remote ischemic preconditioning (RIPC) by analysing the microcirculatory, hemodynamic and histological changes in partial liver ischemia-reperfusion of rats. METHODS: 60-minute partial liver ischemia followed by 120-minute reperfusion was performed without (Control group, n=7) or with preconditioning. In RIPC groups a tourniquet was applied around the left thigh using 3 cycles of 10-minute ischemia/10-minute reperfusion, one (RIPC-1, n=7) or twenty-four hours (RIPC-24, n=7) before I/R. Hemodynamic and microcirculatory measurements were performed before and after ischemia and in 30th, 60th and 120th minute of reperfusion and histological examination at the end of reperfusion. RESULTS: Blood pressure decreased in all groups followed by biphasic changes in Control group. In RIPC groups R120 values returned almost to normal. Heart rate increased in Control and RIPC-1 groups at R120, while RIPC-24 did not show significant changes. Microcirculation of non-ischemic liver stayed constant in Control and showed significant changes in RIPC-24 group, while in ischemic liver elevated by R120 in all groups. RIPC didn't reduce histological alterations. CONCLUSION: Considering the survival and the results, both remote ischemic preconditioning protocols had beneficial effect in hepatic ischemia-reperfusion, however the histopathological findings were controversial.

Is the early or delayed remote ischemic preconditioning the more effective from a microcirculatory and histological point of view in a rat model of partial liver ischemia-reperfusion?

Abstract Purpose: To compare early- and late-effect remote ischemic preconditioning (RIPC) by analysing the microcirculatory, hemodynamic and histological changes in partial liver ischemia-reperfusion of rats. Methods: 60-minute partial liver ischemia followed by 120-minute reperfusion was performed without (Control group, n=7) or with preconditioning. In RIPC groups a tourniquet was applied around the left thigh using 3 cycles of 10-minute ischemia/10-minute reperfusion, one (RIPC-1, n=7) or twenty-four hours (RIPC-24, n=7) before I/R. Hemodynamic and microcirculatory measurements were performed before and after ischemia and in 30th, 60th and 120th minute of reperfusion and histological examination at the end of reperfusion. Results: Blood pressure decreased in all groups followed by biphasic changes in Control group. In RIPC groups R120 values returned almost to normal. Heart rate increased in Control and RIPC-1 groups at R120, while RIPC-24 did not show significant changes. Microcirculation of non-ischemic liver stayed constant in Control and showed significant changes in RIPC-24 group, while in ischemic liver elevated by R120 in all groups. RIPC didn't reduce histological alterations. Conclusion: Considering the survival and the results, both remote ischemic preconditioning protocols had beneficial effect in hepatic ischemia-reperfusion, however the histopathological findings were controversial.

Beneficial effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in the rat.

BACKGROUND: Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. OBJECTIVE: To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. METHODS: In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. RESULTS: Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. CONCLUSIONS: RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results.

Hemorheological and metabolic consequences of renal ischemia-reperfusion and their modulation by N,N-dimethyl-tryptamine on a rat model.

BACKGROUND: Micro-rheological relations of renal ischemia-reperfusion (I/R) have not been completely elucidated yet. Concerning anti-inflammatory agents, it is supposed that sigma-1 receptor agonist N,N-dimethyl-tryptamin (DMT) can be useful to reduce I/R injury. OBJECTIVE: To investigate the micro-rheological and metabolic parameters, and the effects of DMT in renal I/R in rats. METHODS: In anesthetized rats from median laparotomy both kidneys were exposed. In Control group (n = 6) no other intervention happened. In I/R group (n = 10) the right renal vessels were ligated and after 60 minutes the organ was removed. The left renal vessels were clamped for 60 minutes followed by 120-minute reperfusion. In I/R+DMT group (n = 10) DMT was administered 15 minutes before the ischemia. Blood samples were taken before/after ischemia and during the reperfusion for testing hematological, metabolic parameters, erythrocyte deformability and aggregation. RESULTS: Lactate concentration significantly increased and accompanied with decreased blood pH. Enhanced erythrocyte aggregation and impaired deformability were observed from the 30th minute of reperfusion. In I/R+DMT group we found diminished changes compared to the I/R group (lactate, pH, electrolytes, red blood cell deformability and aggregation). CONCLUSIONS: Metabolic and micro-rheological parameters impair during renal I/R. DMT could reduce but not completely prevent the changes in this rat model.

Survey of KI, WU, MW, and STL Polyomavirus in Cancerous and Non-Cancerous Lung Tissues.

BACKGROUND/AIMS: The pathogenesis of the human polyomavirus (PyV) KI, WU, MW, and STL has not been elucidated yet. Respiratory transmission is suggested, but the site of the replication, tissue, and cell tropism is not clarified. KIPyV and WUPyV DNA and/or antigen were detected in normal lung tissues previously by others. In fact, a KIPyV DNA sequence was found in lung cancer samples. Up to date, there is no publication about the DNA prevalence of MWPyV and STLPyV neither in normal nor in cancerous lung tissues. The aim of the present study was to examine the DNA prevalence of these polyomaviruses in cancerous and non-cancerous lung tissue samples, in order to study the possible site for viral replication and/or persistence, and the potential association of these viruses with lung carcinogenesis as well. METHODS: 100 cancerous and 47 non-cancerous, formalin-fixed paraffin-embedded lung tissue samples were studied for KIPyV, WUPyV, MWPyV, and STLPyV by real-time PCR. RESULTS AND CONCLUSION: Neither of the viruses was found in samples from small-cell, non-small-cell (adenocarcinoma, squamous-cell carcinoma and large-cell neuroendocrine lung cancer), mixed-type and non-differentiated lung carcinoma, and non-cancerous lung tissues (from patients with pneumonia, emphysema and fibrosis).

Intestinal ischemia-reperfusion leads to early systemic micro-rheological and multiorgan microcirculatory alterations in the rat.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) is a potentially life-threatening situation and its pathomechanism is not fully understood yet. OBJECTIVE: To investigate the early micro-rheological, microcirculatory and morphological consequences of intestinal I/R in a rat model. METHODS: CD rats were anesthetized and subjected to Control (n = 7) or I/R (n = 7) groups. Left femoral artery cannulation and median laparotomy were performed. In the I/R group the superior mesenteric artery was clamped for 30 minutes. Blood samples were taken before (Base) and after the ischemia, at the 30th, 60th and 120th minutes of the reperfusion (R-30, R-60, R-120). Hematological parameters, erythrocyte deformability and aggregation were determined. On the jejunum, the liver and the right kidney laser Doppler flowmetry tests were completed. At the end of experiment histological samples were taken. RESULTS: Hematocrit, leukocyte and platelet counts increased during the reperfusion. Erythrocyte deformability worsened versus Control. All erythrocyte aggregation index values of I/R group increased gradually. Intestinal microcirculatory blood flux units (BFU) did not recover completely after ischemia, at R-30 liver BFU values were lower, and kidney values decreased by R-120. Histology showed signs of I/R injury. CONCLUSIONS: Micro-rheological parameters may show early and significant deterioration during the reperfusion that might contribute further to microcirculatory alterations.

Peritubular capillary basement membrane multilayering in early and advanced transplant glomerulopathy: quantitative parameters and diagnostic aspects.

The ultrastructural quantitative aspects of peritubular capillary basement membrane multilayering (PTCBML) were examined in 57 kidney transplant biopsies with transplant glomerulopathy (TG). The measurements included three cutoffs [permissive: 1 PTC with 5 basement membrane (BM) layers, intermediate: 3 PTCs with 5 layers or 1 PTC with 7 layers, strict: 1 PTC with 7 layers and 2 PTCs with 5 layers] and the mean number of BM layers (PTCcirc). Two groups were assigned, namely patients with mild TG (Banff cg1a and cg1b) and those with moderate-to-severe TG (cg2 and cg3). Their respective clinical, serological, and morphological characteristics were then compared. The clinical data revealed that mild TG corresponded to early chronic antibody-mediated rejection (cABMR), while moderate-to-severe TG corresponded to the advanced stage of the disease. The permissive threshold displayed the lowest specificity (73 %) and the highest sensitivity (83 %) for moderate-to-severe TG, and its corresponding PTCcirc value was 3 layers. In contrast, the strict threshold-adopted by the Banff 2013 classification-displayed a specificity and sensitivity of 93 and 52 %, respectively, and the corresponding PTCcirc was 4 layers. In mild TG, 26 % of the cases met the permissive cutoff and 6 % the strict cutoff. Mild TG was associated with a lower PTCcirc (2.6 layers vs 4.5 layers in moderate-to-severe TG; p < 0.0001). Amongst the various criteria, the permissive criterion was associated most frequently with mild TG, and had prognostic relevance. Because of this, we propose its usage as a marker of early cABMR-induced PTCBML if non-alloimmune causes of PTCBML can be ruled out.