Oxidative dehalogenation of trichlorophenol catalyzed by a promiscuous artificial heme-enzyme

The miniaturized metalloenzyme Fe(iii)-mimochrome VI*a (Fe(iii)-MC6*a) acts as an excellent biocatalyst in the H₂O₂-mediated oxidative dehalogenation of the well-known pesticide and biocide 2,4,6-trichlorophenol (TCP). The artificial enzyme can oxidize TCP with a catalytic efficiency (k_cat/K^TCP_m = 150 000 mM⁻¹ s⁻¹) up to 1500-fold higher than the most active natural metalloenzyme horseradish peroxidase (HRP). UV-visible and EPR spectroscopies were used to provide indications of the catalytic mechanism. One equivalent of H₂O₂ fully converts Fe(iii)-MC6*a into the oxoferryl-porphyrin radical cation intermediate [(Fe(iv) O)por˙⁺], similarly to peroxidase compound I (Cpd I). Addition of TCP to Cpd I rapidly leads to the formation of the corresponding quinone, while Cpd I decays back to the ferric resting state in the absence of substrate. EPR data suggest a catalytic mechanism involving two consecutive one-electron reactions. All results highlight the value of the miniaturization strategy for the development of chemically stable, highly efficient artificial metalloenzymes as powerful catalysts for the oxidative degradation of toxic pollutants.

The artificial metalloenzyme FeMC6*a is able to perform the H₂O₂-mediated dechlorination of 2,4,6-trichlorophenol with unrivalled catalytic efficiency, highlighting its potential application for the removal of toxic pollutants.     

Postoperative Liver Dysfunction and Future Remnant Liver: Where Is the Limit?

Background The future remnant liver (FRL) limit for safe major hepatectomy with low risk of postoperative liver failure has not yet been well defined. Methods Between April 2000 and September 2004, every patient scheduled for major hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE, associated vascular resection and liver cirrhosis. The FRL was correlated with short-term results in patients with normal liver (group A) and those with impaired liver function secondary to neoadjuvant chemotherapy or cholestasis (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50% and serum bilirubin level >5 mg/100 ml for three or more consecutive days. Results A total of 119 patients were analyzed, 72 in group A and 47 in group B. The FRL value was the only significant risk factor for postoperative liver dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did not correlate with postoperative mortality and morbidity. Bilirubin and prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in both groups. In group A, patients with postoperative liver dysfunction had a FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV. Conclusions Hepatectomy can be considered safe when FRL is >26.5% in patients with healthy liver and >31% in patients with impaired liver function.     

Repeated injection of botulinum toxin a in patients with neurogenic bladder: our experience

Background: In literature, the majority of data about treatment with botulinum toxin A are based on the results of a single treatment. We evaluate the safety and effectiveness in the medium term of the use of botulinum toxin type A in patients with neurogenic bladder, taking into consideration the clinical and urodynamic parameters, particularly in cases with repeated injections. Methods: 25 patients were divided into 2 groups: a first group of patients with detrusor overactivity, and a second with overactive sphincter. We performed 20-30 injections (Dysport), at a dose ranging between 500 and 1000 U. The first group was treated with infiltration in the detrusor and in the detrusor and trigone. The second group received injections in the perisphinteric zone, and in the?perisphinteric zone and bladder neck. Of the 25 patients, 12 received a retreatment: the first group of patients kept a daily voiding diary to record the number of bladder emptying, incontinence episodes, nycturia and urgency of urination. The urodynamic parameters and symptoms pre-treatment and 4 months after the treatment were compared in both groups. Results: In the first group there were significant changes in the cystometric capacity, maximum detrusor pressure, and in the post-void residual urine 4 months after treatment. These patients were satisfied with the treatment because of the improvement of incontinence and episodes of urgency. In 9 out of 15 retreated patients, the therapeutic results were similar to the first treatment. The second group reported significant improvements in maximum urinary flow rate, post-void residual urine and maximum detrusor pressure. 3 out of 10 patients were retreated even in this group; the new therapeutic results were similar to the first treatment. Conclusions: Our results in 25 patients with neurogenic bladder showed a concordance with the literature data. The treatment of detrusor and sphincter neurogenic overactivity with botulinum toxin A is effective and safe. Also in the 12 patients with repeated injection treatment, it has been proven safe and effective.     

Molecular diagnostic tools for the detection of nodal micrometastases in prostate cancer patients undergoing radical prostatectomy with extended pelvic lymph node dissection: a prospective study

Background: Routine pathological examination can miss micro-metastatic tumor foci in the lymph nodes (LN) of patients with prostate cancer (PCa) that undergo radical prostatectomy and pelvic lymph node dissection (PLND). The aim of the present prospective study was to evaluate the impact of micrometastases assessed by serial section (SS), immunohistochemistry (IHC), and Real-time Polymerase Chain Reaction (RT-PCR) in patients undergoing radical prostatectomy with extended PLND. Materials and methods: 32 consecutive patients who underwent radical prostatectomy with extended PLND (obturator, internal/external and distal 2cm common iliac lymph-nodes (LN)) for intermediate (clinical T1c-T2 and PSA:10-20 ng/mL and clinical Gleason Score = 7) or high (clinical stage T3 or PSA>20 or clinical Gleason Score = 8-10) PCa were enrolled. The nodes were processed by the one uropathologist, both according to the routine pathological examination (analysis of the central section for 4 mm nodes or every 2 mm for LN>4 mm), which served as comparative method, both according to SS, IHC with antibodies against PSA and broad-spectrum Cytokeratins (BSCK), and quantitative RT-PCR targeting PSA, PSMA (PS Membrane Antigen), and Glucuronidase-S-Beta (GUSB) mRNA, that are over-expressed in prostatic cancer cells. Results: A total of 628 LN were analyzed, with a mean number of LN removed of 19.6 (SD = 7.2). Applying the routine pathological examination, 10 (31.2%) patients and 23 (3.9%) LN resulted positive for nodal involvement, with mean positive LN of 2.2 (SD = 1.4). After applying the SS and the molecular method of analysis (IHC and RT-PCR), micrometastases were found in 7 LN (SS showed micrometastases in 3 of them, IHC in 6 of them and RT-PCR in 7 of them); a total of 3 (9.3%) node-negative patients showed micrometastases at routine pathological examination (in 2 patients with RT-PCR and in 1 with IHC). Conclusions: The significance of micrometastases in PCa and the potential therapeutic role of PLND is not yet clarified, but the molecular analysis of the LN can detect a significant percentage of patients who harbor micro-metastatic PCa missed at routine pathological examination, and can enhance the accuracy of lymphadenectomy as a staging method.     

Association between trauma and cancer of the testis: the importance of self-palpation of the testis for the early detection: two case reports

introduction: Cancer of the testis is not always early detected and recognised, both by the physician and by the patient: sometimes physicians do not make an accurate genitals exam while patients often underestimate this problem. Case reports: Case I: 42-year-old man accepted from another hospital's Emergency, because of pain and edema of the right testis after a recent trauma on the gonad. At US, evidence of increased volume of the right testis with a large intraparenchymal hematoma. The markers were higher than normal. We performed a right orchiecthomy. The pathologist noted the presence of a mixed cancer of the testis (95% embryonal, 5% seminoma). Case II: 49-year-old man with hematuria, accepted from Emergency. The abdominal US revealed the presence of a voluminous neoformation (diameter of 12 cm) of the right kidney with neoplastic thrombosis of the right kidney vein. At the general physical exam, we detected the presence of an increased right testis, that at the US appared to be suspicious for cancer. Tumor markers were normal with the exception of αFP. We performed right nephro-adrenalectomy, right orchiectomy and removal of local nodes. The definitive histological examination demonstrated the presence of a seminoma of the testis and papillary carcinoma of the kidney with node metastasis. Discussion: Current studies showed an association between trauma and cancer of the testis, even if some authors did not find this association because they consider that patients with trauma undergo US and in that occasion cancer is incidentally detected. Conclusions: The association between trauma and cancer of the testis is controversial in current studies. Furthermore screening for the cancer of the testis does not seem to be useful, even if the self- and the physician's palpation of the testis seem to be very important because in these two cases they should allow the early detection of the condition, with a resulting better prognosis.     

Is proliferative colonic disease presentation changing?

AIM: To compare the site, age and gender of cases of colorectal cancer (CRC) and polyps in a single referral center in Rome, Italy, during two periods.METHODS: CRC data were collected from surgery/pathology registers, and polyp data from colonoscopy reports. Patients who met the criteria for familial adenomatous polyposis, hereditary non-polyposis colorectal cancer syndrome or inflammatory bowel disease were excluded from the study. Overlap of patients between the two groups (cancers and polyps) was carefully avoided. The χ² statistical test and a regression analysis were performed.RESULTS: Data from a total of 768 patients (352 and 416 patients, respectively, in periods A and B) who underwent surgery for cancer were collected. During the same time periods, a total of 1693 polyps were analyzed from 978 patients with complete colonoscopies (428 polyps from 273 patients during period A and 1265 polyps from 705 patients during period B). A proximal shift in cancer occurred during the latter years for both sexes, but particularly in males. Proximal cancer increased > 3-fold in period B compared to period A in males [odds ratio (OR) 3.31, 95%CI: 2.00-5.47; P < 0.0001). A similar proximal shift was observed for polyps, particularly in males (OR 1.87, 95%CI: 1.23-2.87; P < 0.0038), but also in females (OR 1.62, 95%CI: 0.96-2.73; P < 0.07).CONCLUSION: The prevalence of proximal proliferative colonic lesions seems to have increased over the last decade, particularly in males.     

Hepatitis E Virus Genotype 4 Outbreak,Italy, 2011

During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.