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We present the first case of salvage retroperitoneal lymph node dissection based on the results of (18)F-FACBC PET/CT performed for a prostate-specific antigen relapse after radical prostatectomy. The patients underwent (11)C-choline PET/CT, which turned out negative, while (18)F-FACBC PET/CT visualized two lymph node metastases confirmed at pathological examination. Preliminary clinical reports showed an improvement in the detection rate of 20-40% for (18)F-FACBC in comparison with (11)C-choline, rendering the (18)F-FACBC the potential radiotracer of the future. Salvage surgery for prostate cancer is a fascinating but controversial approach. New diagnostic tools may improve its potential by increasing the assessment and the selection of the patients.

OBJECTIVES: To evaluate the influence of preservation of the muscular internal sphincter and proximal urethra on continence recovery after radical prostatectomy. METHODS: This was a prospective single-center, case-control study. A total of 40 consecutive patients with organ-confined prostate cancer were submitted to radical prostatectomy with the preservation of the muscular internal sphincter and the proximal urethra (group 1), and their outcomes were compared with those of 40 patients submitted to a standard procedure (group 2). Continence rates were assessed using a self-administrated questionnaire at 3, 7 and 30 days, and 3 and 12 months after removal of the catheter. RESULTS: Group 1 had a faster recovery of early continence than group 2 at day 3 (45% vs 22%; P = 0.029) and at day 7 (75% vs 50%; P = 0.018). Considering the number of pads, group 1 had a faster recovery of continence at 3, 7 and 30 days, and also had less incidence of severe incontinence. There was no statistically significant difference in terms of continence at 3 and 12 months among the two groups. Multivariate logistic regression analysis showed that surgical technique and young age were significantly associated with earlier time to continence at 3 and 7 days. The two groups had no significant differences in terms of surgical margins. CONCLUSIONS: Our modified technique of radical retropubic prostatectomy with preservation of the smooth muscular internal sphincter, as well as of the proximal urethra during bladder neck dissection, results in a significantly increased urinary continence at 3, 7 and 30 days after catheter removal, with a minor incidence of severe incontinence. The technique is also oncologically safe, and it does not increase the operative duration of the procedure.

The short-term lipid-lowering activity of some nutraceuticals is well-known, however there is a lack of knowledge about their long-term effect, especially as it regards insulin-resistance parameters and biomarkers of vascular health. This study is a 12-months follow-up randomized clinical trial carried out on 269 non smoker hyperlipidaemic patients in primary prevention for cardiovascular disease, 214 of them (129 men and 85 women) completed the trial with a good compliance. All the subjects were non diabetics nor treated with antihyperlipidaemic drugs. 79 normoweight subjects (Group1) were treated with a combined nutraceutical (Armolipid Plus ® - ALP, Rottapharm-Madaus SpA, Monza, I) associated with a standardized TLS (therapeutic life-style as in the definition of third Adult Treatment Panel of the National Cholesterol Education Program), 85 overweight with ALP-TLS (Group 2), and 50 overweight with just intensified TLS (Group 3). Efficacy parameters (BMI, FPG, FPI, HOMA index,MMP-2, MMP-9, TIMP-1, TIMP-2, TC, LDL-C,HDL-C, TG) were evaluated every 4 months. Educational reinforcements were also planned every 4 months. This study demonstrated the long-term efficacy and safety of a combined nutraceutical added to therapeutic life-style in overweight and normoweight dyslipidaemic subjects; berberine and red yeast rice based nutraceuticals showed efficacy on body weight reduction and insulin-sensitivity promotion in non diabetic hyperlipidaemic patients; favourable effects of a combined nutraceutical added to therapeutic life-style were observed on biomarkers of vascular remodelling in overweight and normoweight dyslipidaemic subjects.

Ulcerative colitis and Crohn's disease are relapsing and remitting chronic disorders. So far, endoscopy is the gold standard for their diagnosis, but less invasive diagnostic biomarkers are needed. Many authors have developed techniques to individuate biomarkers such as genetic testing factor or proteins in biological samples such as serum, plasma, and cellular subpopulations. A protein fingerprint pattern, patient-unique, specific for the diagnosis of inflammatory bowel disease (IBD) and potentially able to predict the future patterns of disease and to help in diagnosis, treatment, and prognosis is of increasing interest among researchers. Nowadays, a proteomic approach may be used in the identification of major alterations of proteins in IBD, but there is still a lack in the identification of a panel of biomarkers among a significant number of patients in large clinical trials. In this review, we analyze and report the current knowledge in proteomic application and strategies in the study of IBD.

Objective: To assess the economic impact of Holmium laser enucleation of prostate (HoLEP) in comparison with transurethral resection of prostate (TURP) and open prostatectomy (OP). Methods: Between January 2017 and January 2018, we prospectively enrolled 151 men who underwent HoLEP, TURP or OP at tertiary Italian center, due to bladder outflow obstruction symptoms. Patients with prostate volume ≤ 70 cc and those with prostate volume > 70 cc were scheduled for TURP or HoLEP and OP or HoLEP, respectively. Intraoperative and early post-operative functional outcomes were recorded up to 6 months follow up. Cost analysis was carried out considering direct costs (operating room [OR] utilization costs, nurse, surgeons and anesthesiologists’ costs, OR disposable products costs and OR products sterilization costs), indirect costs (hospital stay costs and diagnostics costs) and global costs as sum of both direct and indirect plus general costs related to hospitalization. Cost analysis was performed comparing patients referred to TURP and HoLEP with prostate volume ≤ 70 cc and men underwent OP and HoLEP with prostate volume > 70 cc respectively. Results: Overall, 53 (35.1%), 51 (33.7%) and 47 (31.1%) were scheduled to HoLEP, TURP and OP, respectively. Both TURP, HoLEP and OP proved to effectively improve urinary symptoms related to BPE. Considering patients with prostate volume ≤ 70 cc, median global cost of HoLEP was similar to median global cost of TURP (2151.69 € vs. 2185.61 €, respectively; p = 0.61). Considering patients with prostate volume > 70 cc, median global cost of HoLEP was found to be significantly lower than median global cost of OP (2174.15 € vs. 4064.97 €, respectively; p ≤ 0.001). Conclusions: Global costs of HoLEP are comparable to those of TURP, offering a cost saving of only 11.4 € in favor of HoLEP. Conversely, HoLEP proved to be a strong competitor of OP because of significant global cost sparing amounting to 1890.82 € in favor of HoLEP.

Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the 'high normal blood pressure' or 'stage 1 hypertension', so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.

AIM: The aim of this study was to evaluate the role of C-choline PET/CT in the preoperative evaluation of the nodal involvement of patients with bladder carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node dissection in comparison with contrast-enhanced CT (CECT) using the pathologic specimen as reference standard. PATIENTS AND METHODS: Twenty-six consecutive patients (69.5 ± 9.3 years; range, 49-84) with histologically proven transitional cell BC were treated with radical cystectomy and pelvic lymph node dissection and were enrolled from April 2011 to January 2013. In all patients, paravesical, internal, eternal, and common iliac nodes as well as obturatory, presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the origin of the inferior mesentery artery. The areas of the LN dissection were grouped as follow: region A included preaortic and precaval LNs; region B included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the right pelvis; region C included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the left pelvis. C-choline PET/CT and abdominal CECT were used to assess the presence of lymph node metastases on a per patient, region, and lesion analysis using the results of surgical specimens obtained at operation as criterion standard. RESULTS: Seven of 26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844 LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a patient-based analysis, C-choline PET/CT showed a sensitivity of 42% and specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of 89%. On a region-based analysis, C-choline PET/CT showed a sensitivity of 11% and specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of 80%. On a lesion (LN)-based analysis, C-choline PET/CT showed a sensitivity of 10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and specificity of 63%. CONCLUSIONS: C-choline PET/CT could provide additional diagnostic information in preoperative nodal staging of patients with invasive BC in comparison with CECT. A study with a larger population should determine if C-choline PET/CT could be recommended as a routine technique in high-risk patients with BC

Chlamydia pneumoniae and human cytomegalovirus (HCMV) are intracellular pathogens able to infect hepatocytes, causing an increase in serum triglycerides and cholesterol levels due to the production of inflammatory cytokines. We investigated whether these pathogens could interfere with cholesterol metabolism by affecting activity of hepatic cholesterol 7α-hydroxylase ( CYP7A1 ) promoter. CYP7A1 is the rate-limiting enzyme responsible for conversion of cholesterol to bile acids, which represents the main route of cholesterol catabolism. A straightforward dual-reporter bioluminescent assay was developed to simultaneously monitor CYP7A1 transcriptional regulation and cell viability in infected human hepatoblastoma HepG2 cells. C. pneumoniae and HCMV infection significantly decreased CYP7A1 promoter activity in a dose-dependent manner, with maximal inhibitions of 33 ± 10% and 32 ± 4%, respectively, at a multiplicity of infection of 1. To support in vitro experiments, serum cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and glucose levels were also measured in Balb/c mice infected with C. pneumoniae. Serum cholesterol and triglycerides also increased in infected mice compared with controls. Although further investigation is required, this work presents the first experimental evidence that C. pneumoniae and HCMV inhibit CYP7A1 gene transcription in the cultured human hepatoblastoma cell line.

Impaired gallbladder motility is a contributing factor to gallstone formation. Since many drugs delaying intestinal motility inhibit gallbladder emptying, the aim of the present study was to evaluate the effect on gallbladder and sphincter of Oddi motility of a Natural Chestnut Wood Extract (NEC) that reduces intestinal motility. In order to evaluate the effect of the extract in normal- and high-risk gallstone conditions, the investigation was performed using tissues from animals fed normal and lithogenic diet. Fifty guinea pigs were administered either control or lithogenic diet. The spontaneous motility of the gallbladder and sphincter of Oddi were recorded on isolated gallbladder tissues; thereafter, the effect of NEC on motility was tested and compared with carbachol (CCh), potassium chloride (KCl), noradrenaline (NA), and A71623. Compared to controls, the lithogenic diet induced an irregular and disordered motor pattern in both the gallbladder and sphincter of Oddi. NEC increased gallbladder and decreased sphincter of Oddi spontaneous motility independently of cholinergic, adrenergic, and CCK-1 receptor-mediated pathways both in controls and in lithogenic diet-fed animals, although the effect was lower in the latter group. The effect was reversible and mediated by calcium channels. The natural extract of chestnut increasing gallbladder contraction and inducing the relaxation of the sphincter of Oddi can be of benefit in pathological conditions associated with increased transit time at risk of gallstones.

We present the first case of salvage radiotherapy based on the results of 18F-FACBC PET/CT performed for a PSA relapse after radical prostatectomy. The patients underwent 11CCholine PET/CT and multiparametric MRI that were negative while 18F-FACBC PET/CT visualized a suspected local relapse confirmed by transrectal ultrasound-guided biopsy. No distant relapse was detected. Thus the patient was submitted to salvage radiotherapy in the prostatic fossa. After 20 months of follow-up, the PSA was undetectable and 18F-FACBC PET/CT was negative. Salvage radiotherapy after surgery, provided that it is administered at the earliest evidence of the biochemical relapse, may improve cancer control and favourably influence the course of disease as well as the adjuvant approach. New imaging techniques may increase the efficacy of the salvage radiotherapy thus helping in the selection of the patients. Preliminary clinical reports showed an improvement in the detection rate of 20-40% of 18F-FACBC in comparison with 11C-Choline for the detection of disease relapse after radical prostatecomy, rendering the 18F-FACBC the potential radiotracer of the future for prostate cancer.

Experts’ summary:In a recently published paper in European Urology, Touijer and coworkers noted that pathologic Gleason score, as well as the number of positive nodes, was significantly correlated with prostate cancer (PCa) outcome in one of the largest retrospective series of node-positive patients after radical prostatectomy (RP) without adjuvant therapy (369 consecutive patients). The study showed that for each year without biochemical recurrence (BCR), the probability of BCR-free survival increases annually to approximately 80% after 5 yr. The Gleason score and the number of positive nodes were important predictors of metastasis-free and BCR-free survival on multivariate analysis. The main message of the paper by Toujier and coworkers is that node-positive patients can have a good prognosis (in terms of survival) even without adjuvant therapy; however, the authors stressed that node-positive patients are not all at the same risk of cancer-specific death. Even if some limitations in the study design must be noted—for example, the lymph node density was not considered, the Gleason score can vary significantly throughout such a long study period, and there was a single-center source of data—the authors confirm a good outcome for node-positive patients with low metastatic tumor burdens.Experts’ comments:The concept that patients with low-volume metastasis have significantly higher survival rates than patients with a high-volume metastatic pattern is quite instinctive. Similar to Touijer et al., we recently reported on our series of 98 node-positive patients and found that patients with one to three positive lymph nodes had higher cancer-specific and overall survival than patients with more than three positive nodes. We stratified our patients into three risk-group categories according to number of positive nodes and Gleason score to better predict oncologic outcomes and found considerable differences in terms of cancer-specific and overall survival [1]. The idea that a proportion of node-positive patients with low tumor burden treated with RP plus extended pelvic lymph node dissection (PLND) might have optimal survival even without adjuvant or salvage therapy is attractive and could support an aggressive approach to treatment in such patients. This idea leads us to the following question: Is metastatic PCa a single risk category to be treated with an identical, mild, and remissive approach? Unlike other malignancies [2], the therapeutic role of regional lymph node dissection in PCa is still uncertain, and the metastatic pattern of PCa cells is not completely understood. However, tumor dissemination in bone vessels or lymphatic vessels can follow different patterns both biologically and chronologically [3]. In the initial phase of the metastatic pattern, some patients might have tumor dissemination only in the pelvic nodes without bone dissemination; thus, in a very carefully selected group of these patients, an extended PLND and RP could be sufficient to treat the disease. Indeed, what is the sense of performing RP to treat high-risk PCa while leaving PCa cells behind in the pelvic nodes? In contrast, if metastatic cells are already present in the bones of node-positive patients at the time of primary treatment and the spread involves lymphatics and bones simultaneously, these cells will remain quiescent for many years. For now, a complete lymphadenectomy plus RP or complete pelvic irradiation administered in the setting of multimodal therapy is the only option available that could help to reduce the tumor volume and help render the PCa a chronic disease with slowed progression. Unfortunately, the current radiologic and molecular diagnostic armamentarium is not adequately accurate to rule out bone metastases, so prompt therapy must be given to patients at high risk of micrometastasis. We hope that new promising radiotracers such as 18F-fluorocyclobutyl-1-carboxylic acid positron emission tomography/computed tomography might become helpful options in the early identification of bone or lymphatic involvement to better address the optimal therapeutic approach in the future [4]. In conclusion, we completely agree with Touijer and coworkers that not all patients with node-positive PCa have the same risk of cancer-specific death and that stratification can help identify those patients with few lymph node metastases who might expect a better prognosis.

none 12 Spermatocytic Seminoma (SS) is less common than the Classic variant, as its incidence ranges between 1.3% and 2.3% of all seminomas. Generally SS is diagnosed in men older than 50 years. The Anaplastic variant of Spermatocytic Seminoma is characterized by an earlier onset when compared to SS, but a benign behavior in spite of its histological patterns similar to Classic Seminoma. We reported the first case of bilateral, largest and synchronous Anaplastic Spermatocytic Seminoma, in a patient treated with radical orchifunicolectomy alone and with long-term follow-up. The currently available data show that Anaplastic SS reveals a clinically benign behavior, and no distant metastases have been reported so far. A close surveillance after surgery could be considered a valid option in the management of this rare testicular neoplasm Gentile G; Giunchi F; Schiavina R; Franceschelli A; Borghesi M; Zukerman Z; Cevenini M; Vagnoni V; Romagnoli D; Colombo F; Martorana G; Brunocilla E Gentile G; Giunchi F; Schiavina R; Franceschelli A; Borghesi M; Zukerman Z; Cevenini M; Vagnoni V; Romagnoli D; Colombo F; Martorana G; Brunocilla E

none 7 OBJECTIVE: We describe our technique for preservation of the smooth muscular internal (vesical) sphincter and proximal urethra during radical retropubic prostatectomy (RRP) and present our preliminary clinical results. MATERIALS AND METHODS: The first steps of the prostatectomy reflect the standard RRP, while for the final phases the procedure continues in an anterograde manner with incision of the fibers of the detrusor muscle at the insertion of the ventral surface of the base of the prostate. At this level, the inner circular muscle of the bladder neck forms a sphincteric ring of smooth muscle that covers the longitudinally oriented smooth muscle component of the urethral musculature that extends distally to the verumontanum. These two proximal structures represent the internal sphincter that envelopes and locks the proximal urethra. A blunt dissection is continued until the ring shaped vesical sphincter is separated from the prostate and the longitudinally oriented smooth muscle component of the urethral musculature is identified. The base of the prostate is then gently separated from the urethra and from the bladder until the maximal length of the urethral musculature is isolated and preserved. RESULTS: After 30 initial set-up procedures, 40 consecutive patients with organ confined prostate cancer were submitted to radical retropubic prostatectomy with the preservation of muscular internal sphincter and the proximal urethra and compared to 40 patients submitted to standard procedure who served as control group. The group of patients submitted to our technical modification had a faster recovery of early continence than control group at 3 and 7 days. CONCLUSIONS: The described technique is a feasible and safe method for preservation of the and allows improving the early recovery of urinary continence. The technique does not increase the rate of positive margins and the duration of the procedure. Brunocilla E; Schiavina R; Borghesi M; Pultrone C; Cevenini M; Vagnoni V; Martorana G Brunocilla E; Schiavina R; Borghesi M; Pultrone C; Cevenini M; Vagnoni V; Martorana G

Objectives To evaluate the influence of preservation of the muscular internal sphincter and proximal urethra on continence recovery after radical prostatectomy (RP). Materials and methods Fifty-five consecutive patients with organ confined prostate cancer were submitted to RP with the preservation of muscular internal sphincter and the proximal urethra (group 1) and compared to 55 patients submitted to standard procedure (group 2). Continence rates were assessed using a self-administrated questionnaire at 3, 7, 30 days and 3, 12 months after removal of the catheter. Results Group 1 had a faster recovery of continence than group 2 at 3 days (50.9% vs. 25.5%; p = .005), at 7 days (78.2% vs. 58.2%; p = .020), at 30 days (80.0% vs. 61.8%; p = .029) and at 3 months (81.8% vs. 61.8%; p = .017); there were no statistical difference in terms of continence at 12 months among the two groups. Multivariate logistic regression analysis of continence showed that surgical technique was significantly associated with earlier time to continence at 3 and 7 days. The two groups had no significant differences in terms of surgical margins. Conclusions Our modified technique of RP with preservation of smooth muscular internal sphincter as well as of the proximal urethra during bladder neck dissection resulted in significantly increased early urinary continence at 3, 7, 30 days and 3 months after catheter removal. The technique does not increase the rate of positive margins and the duration of the procedure.

Ulcerative colitis (UC) is a chronic inflammatory condition of the rectum and colon. The conventional medical treatment of inflammatory bowel disease (IBD) involves anti-inflammatory, immunosuppressive drugs and antibiotics.1 Recently, considerable attention has been given to the identification of naturally occurring substances, particularly those present in dietary and medicinal plants as a useful tool in the prevention and treatment of many pathological conditions. Turmeric (Curcuma longa L.) is extensively used in Ayurvedic medicine as a treatment for several inflammatory and functional conditions of the gastrointestinal tract such as diarrhea. Since intestinal motility has been reported to be impaired in IBD patients, our investigation was aimed at evaluating whether turmeric, besides its anti-inflammatory properties, exerts also a myorelaxant effect on the intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium (DSS) administration (5% and 2.5%,w/v, respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Similarly Curcuma extract was administered to healthy mice and in vitro evaluated in healthy intestine. The biological activity of Curcuma extract was evaluated towards Carbachol induced contraction in isolated ileum and colon in healthy animals, acute and chronic colitis animals and after administration of Curcuma.3 Curcuma extract reduced the spontaneous contractions in the ileum and colon both in the healthy intestine and in the pathological intestinal strips. In addition, it inhibited the maximal response to Carbachol in a non-competitive and reversible manner. Similar results were observed in ileum and colon from Curcuma fed mice. The administration of DSS reduced the motility, mainly in the colon; Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet; however a prolonged administration of Curcuma, once the mucosal damage of the intestine was repaired, reduced the spontaneous and Carbachol-induced contractions.3 Curcuma extract has been shown to exert a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The effect is reversible and non-competitive and it is present also in the normal intestine. These results suggest the use of curcuma extract as a spasmolytic agent 3 not only in IBD, but also as a useful tool in the management of functional disorders References 1. Bossa, F.; Colombo, E.; Andriulli, A.; Annese, V. Treatment of steroid-naive ulcerative colitis. Expert Opin Pharmacother, 2009, 10, 1449-1460. 2. Jurenka, J.S. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev, 2009, 14, 141-153. 3. Aldini, R.; Budriesi, R.; Roda, G.; Micucci, M.; Ioan, P.; D’Errico-Grigioni, A.; Sartini, A.; Guidetti, E.; Marocchi, M.; Cevenini, M.; Rosini, F.; Montagnani, M.; Chiarini, A.; Mazzella, G. Effect of Curcuma longa extract on the intestinal motility in acute and chronic DSS induced colitis in mice. Plose One, 2012, 7, e44650.

BackgroundCurcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse.MethodsThirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied.ResultsIn the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed.ConclusionsAlthough these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

BACKGROUND: Curcuma has long been used as an anti-inflammatory agent in inflammatory bowel disease. Since gastrointestinal motility is impaired in inflammatory states, the aim of this work was to evaluate if Curcuma Longa had any effect on intestinal motility. METHODS: The biological activity of Curcuma extract was evaluated against Carbachol induced contraction in isolated mice intestine. Acute and chronic colitis were induced in Balb/c mice by Dextran Sulphate Sodium administration (5% and 2.5% respectively) and either Curcuma extract (200 mg/kg/day) or placebo was thereafter administered for 7 and 21 days respectively. Spontaneous contractions and the response to Carbachol and Atropine of ileum and colon were studied after colitis induction and Curcuma administration. RESULTS: Curcuma extract reduced the spontaneous contractions in the ileum and colon; the maximal response to Carbachol was inhibited in a non-competitive and reversible manner. Similar results were obtained in ileum and colon from Curcuma fed mice. DSS administration decreased the motility, mainly in the colon and Curcuma almost restored both the spontaneous contractions and the response to Carbachol after 14 days assumption, compared to standard diet, but a prolonged assumption of Curcuma decreased the spontaneous and Carbachol-induced contractions. CONCLUSIONS: Curcuma extract has a direct and indirect myorelaxant effect on mouse ileum and colon, independent of the anti-inflammatory effect. The indirect effect is reversible and non-competitive with the cholinergic agent. These results suggest the use of curcuma extract as a spasmolytic agent.

Alisporivir (DEB025), a cyclosporin A derivative, is a new antiviral drug which targets host cell factors (cyclophilins) inhibiting viral replication without immunosuppressive effects. This drug potently inhibits cyclophilin-dependent HCV replication with an additive antiviral effect to standard-of-care (SoC) therapy for HCV. The administration of alisporivir in addition to SoC enhances activity against all HCV genotypes, with a good safety profile. Currently, two trials are ongoing: a Phase III and a Phase II trial assessing the efficacy of alisporivir plus SoC in genotype-1 treatment-naive patients and nonresponders or relapsers. Another Phase II study is examining the potential use of alisporivir for IFN-free treatment in HCV genotype 2 and 3 patients naive to treatment. In this review, we describe the unique characteristics of this cyclophilin inhibitor and benefit afforded by this drug in combination therapy with current and future HCV treatments.