Marius Kincius

Effects of ischemia-reperfusion and pretreatment with mildronate on rat liver mitochondrial function

Mildronate (3-(2,2,2-trimethylhydrazinium) propionate), which is mostly used in cardiological practice and is considered an anti-ischemic drug, was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation. Recently it was shown that the mitochondrial respiratory chain may also be a target for mildronate action. In this study, we aimed to investigate whether mildronate can protect the liver against a 90-min normothermic ischemia/30-min reperfusion-induced mitochondrial dysfunction. Rats were pre-treated for one or two weeks with mildronate (100 mg/kg/day or 200 mg/kg/day) or Ringer solution and subjected to ischemia/reperfusion.We found that ischemia/reperfusion caused a decrease in mitochondrial State 3 respiration rate and in the respiratory control index (RCI), and an increase in State 2 respiration rate with succinate, glutamate + malate and palmitoyl-L-carnitine + malate. One or two weeks of pre-treatment of rats with different doses of mildronate did not reduce the ischemia/reperfusion-induced decrease in the State 3 respiration rate or RCI; however, a one week pre-treatment slightly diminished the increase in the State 2 respiration rate with glutamate + malate substrates. The leakage of the liver enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase, was similar in both the untreated and pre-treated with mildronate groups. No steatotic livers were observed in any experimental groups after mildronate pre-treatment. In conclusion, 90 min of liver ischemia followed by a 30 min reperfusion has a deleterious effect on rat liver mitochondrial function. Mildronate pre-treatment of rats at doses of 100 or 200 mg/kg/day for one or two weeks did not prevent ischemia/reperfusion-induced mitochondrial dysfunction and liver injury.

Evaluation of LRINEC Scale Feasibility for Predicting Outcomes of Fournier Gangrene.

BACKGROUND Fournier gangrene (FG) is a fulminant necrotizing infection of the perineal, perianal, and periurethral tissues. The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) scale is used for diagnosis of necrotizing fasciitis. However, data on its relevance and usefulness in FG are lacking. The aim of this study was to evaluate the utility of the LRINEC scale in predicting the outcome of FG. METHODS This retrospective case study included 41 patents with FG treated at our institution from 2000 to 2013. The patients were divided into survivors and non-survivors. RESULTS The mortality rate was 22%. The median age (75 vs. 62.5 y; p = 0.013), rate of co-existing diabetes mellitus (66.7% vs. 3.1%; p < 0.001), and median affected skin surface (4% vs. 1%; p < 0.001) were greater in the non-survivors. Seven of nine patients (77.8%) who did not survive (compared with 37.5% who survived) had a polymicrobial infection (p = 0.032). Of all the causative pathogens isolated, Proteus mirabilis was more common in non-survivors (55.6% vs. 6.3%; p = 0.001). The median calculated LRINEC score for survivors was 5 compared with 10 for the non-survivors (p < 0.001). Regression analysis showed that all the aforementioned variables, except for polymicrobial culture, were significant risk factors for predicting death. The area under the receiver operating characteristic curve for the LRINEC score was the highest, 0.976 (95% confidence interval 0.872-0.999; p < 0.0001), and the cut-off value was ≥9 with 93.7% specificity and 100% susceptibility for the prediction of a lethal outcome. CONCLUSIONS The LRINEC score could be used for prediction of disease severity and outcomes. A threshold of 9 could be a high-value predictor of death during the initial evaluation of patients with FG.

Importance of prostate volume and urinary flow rate in prediction of bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia

Objectives To predict bladder outlet obstruction with parameters of non-invasive investigations for patients with symptomatic benign prostatic hyperplasia. Patients and methods A sample of 122 men with moderate to severe lower urinary tract symptoms suggestive of benign prostatic hyperplasia was selected. Transrectal prostate ultrasound, free flow measurement, and transabdominal ultrasound for residual urine were carried out together with digital rectal examination for all patients. All patients underwent urodynamic pressure/flow test. Two groups of obstructed (91 patient) and equivocal/unobstructed (31 patient) were analyzed. Probabilistic model based on logistic regression was developed for prediction of obstruction. Results Various parameters were compared in obstructed and non-obstructed/equivocal groups, highlighting important parameters for obstruction. Correlation analysis indicates higher obstruction dependence on average and peak flow rates and lower dependence on total prostate and transition zone volumes, transition zone index. Binary logistic regression model suggests that average flow rate combined with total prostate volume is the best predictor of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analyzed sample. The analyzed model suggests that peak flow rate could also be almost equally important parameter instead of average flow rate. Conclusions The study suggests that average/peak flow rate combined with total prostate volume can be used for prediction of obstruction. The developed probabilistic model helps to determine patients who need invasive urodynamic testing for decision on surgical treatment.

factors predicting gleason score 6 upgrading after radical prostatectomy

Objectives Prostate cancer Gleason score 6 is the most common score detected on prostatic biopsy. We analyzed the clinical parameters that predict the likelihood of Gleason score upgrading after radical prostatectomy. Methods The study population consisted of 241 patients who underwent radical retropubic prostatectomy between Feb 2002 and Dec 2007 for Gleason score 6 adenocarcinoma. The influence of preoperative parameters on the probability of a Gleason score upgrading after surgery was evaluated using multivariate logistic regression and ROC curves. Results Gleason score upgrade was found in 92 of 241 patients (38.2%). Multivariate logistic regression analysis showed that only percentage of cancer in dominant lobe and prostate weight were significant predictors for Gleason score upgrading (p = 0.043 and p = 0.006, respectively). ROC curves showed that prostate weight and PSA density were only two independent significant parameters for prediction of upgrade (AUC – 0.634, p <0.0001 and 0.604, p = 0.006, respectively). Gleason score upgrading was observed to be accompanied by significantly higher rates of extra prostatic extension (p <0.001) and seminal vesicle invasion (p = 0.002). Conclusions Almost forty percent of tumors graded Gleason 6 at biopsy are Gleason 7 at surgery. Upgraded tumors significantly associated with adverse pathological features. The probability of Gleason score upgrade can be predicted using prostate weight and PSA density as independent parameters.

Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis

The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats.

Outcome of surgery in locally advanced pT3a prostate cancer.

Introduction The aim of this study is to present the oncologic outcomes and to determine prognostic parameters of overall (OS), cancer specific survival (CSS), disease progression free survival (DPFS) and biochemical progression free survival (BPFS) after surgery for pT3a prostate cancer (PCa). Material and methods Between 2002 and 2007, a pT3a stage after radical prostatectomy was detected in 126 patients at our institution. Kaplan-Meier analysis was used to calculate OS, CSS, DPFS and BPFS. Cox regression was used to identify predictive factors of survival. Results Five-year OS, CSS, DPFS and BPFS rates were 96%, 98.7%, 97.3% and 60%, respectively. Among patients with prostate specific antigen (PSA) <10 ng/ml and PSA >20 ng/ml the 5-year OS was 98.8% and 80%, respectively, whereas 5-year BPFS was 66% and 16.6%, respectively. Survival was different when comparing surgery Gleason score ≤7 and ≥8. 5-year OS and BPFS were 98% vs. 80%, and 62.6% vs. 27.3%, respectively. Specimen Gleason score and preoperative PSA were significant predictors of BPFS. The risk of biochemical progression increased up to 2-fold when a Gleason score ≥8 was present at final pathology. Conclusions In locally advanced pT3 PCa, surgery can yield very good cancer control and survival rates especially in cases with PSA <10 ng/ml and Gleason score ≤7. PSA and Gleason score after surgery are the most significant predictors of outcomes after radical prostatectomy.

Independent predictors of biochemical recurrence after radical prostatectomy: a single center experience

Introduction The aim of study was to establish pretreatment and postoperative factors which could predict the early biochemical recurrence after radical prostatectomy. Materials and method 754 patients had undergone radical prostatectomy since January 2002 to December 2008 in our department and were included in this prospective study. Exclusion criteria were: neoadjuvant or adjuvant treatment (radiation or hormonal treatment) and N+. Following parameters were evaluated: age, PSA at time of biopsy, time period from biopsy to operation, biopsy and postoperative Gleason score, stage, high grade intraepithelial neoplasias, perineural invasion. Biochemical recurrence was detected if PSA value after radical prostatectomy was ≥0.2 ng/ml. All factors likely to be predictive were evaluated by univariate analysis (Log-rank test). Multivariate analysis using Cox model was completed for all factors with p value <0.1 at univariate analysis. Results Final analysis was done using data of 496 patients. We detected 53 (10.7%) biochemical recurrences. Calculated actuarial biochemical recurrence free survival reached 64%. Multivariate analysis highlighted that PSA >10 ng/ml (HR 2.45, p = 0.008), pathological stage ≥pT3 (HR 2.371, p = 0.02), postoperative Gleason score ≥7 (HR 2.149, p = 0.049), positive surgical margins (HR 2.482, p = 0.014) and absence of high grade intraepithelial neoplasia in removed prostate (HR 0.358, p = 0.006) are independent factors influencing biochemical recurrence after radical prostatectomy. Conclusion Patients with higher PSA, locally advanced disease, positive surgical margins, and Gleason score ≥7 are at the highest risk for biochemical recurrence.