Palladium and platinum complexes based on pyridine bases induced anticancer effectiveness via apoptosis protein signaling in cancer cells.

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1-4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1-4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1-4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1-4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1-4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1-4 and cisplatin could induce p53. All complexes 1-4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.

Potential Anticancer Activities and Catalytic Oxidation Efficiency of Platinum(IV) Complex.

The treatment of an aqueous acetonitrile solution of chloroplatinic acid hydrate H2PtCl6.xH2O and pyridine-2-carbaldehyde-oxime (paOH) in the presence of potassium thiocyanate at room temperature (25°) led to the formation of a new Pt(IV) complex with the formula [Pt(SCN)2(paO)2], (1). Complex 1 was fully characterized by FT-IR, UV-vis and NMR spectroscopic techniques as well as elemental analysis. The crystallographic structure of complex 1 was obtained by single-crystal X-ray diffraction. The structure of complex 1 consists of a distorted octahedral geometrical environment around the platinum center in which the coordination sites are occupied by two terminal thiocyanate ligands in trans arrangement and two bidentate paO ligands through four nitrogen atoms. In addition, the in vitro evaluation of the cytotoxicity of platinum complex 1 against four different cancer cell lines was performed. The IC50 values for colon (HCT116), liver (HepG2), breast (MCF-7) and erythroid (JK-1) treated with complex 1 are 19 ± 6, 21 ± 5, 22 ± 6, and 13 ± 3 µM, respectively. In HCT116 cells treated with the IC50 dose of our title compound, apoptosis and necrosis were increased by 34% and 27.8%, respectively. Cells halted in the proliferative phase (S phase) to 21.7 % and 29.8% in HCT116 and HepG2 cells treated with complex 1 have anti-proliferative actions. Furthermore, the catalytic activity of synthesized complex 1 was examined in the oxidation reaction of benzyl alcohols in the presence of an oxidant. Finally, the luminescence behavior of complex 1 was investigated.

Retzius-sparing robot-assisted radical prostatectomy versus open retropubic radical prostatectomy: a prospective comparative study with 19-month follow-up.

BACKGROUND: The aim of the present study was to compare the surgical outcomes of retzius-sparing robot-assisted radical prostatectomy (RS-RARP) and open retropubic radical prostatectomy (ORP). METHODS: We included patients with clinically localized prostate cancer who underwent RS-RARP or ORP and met our inclusion criteria. We compared the perioperative, oncological, and continence outcomes between both surgical approaches. Continence function was assessed using the validated International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form. Continence was defined as using 0-1 safety pad per day. Biochemical recurrence (BCR) was defined as two consecutive rises in serum PSA more than 0.2 ng/mL. Events of local recurrence, distant metastasis, and cancer death were reported and compared using Kaplan-Meier survival analysis. RESULTS: Between 1 June 2013 and 1 October 1 2016, 184 men were enrolled, of whom 125 underwent RS-RARP and 59 underwent ORP. Baseline demographic and pathological characteristics were similar between both groups (P>0.05). Patients in RS-RARP group had significantly lower blood loss, fewer transfusion rates, lower VAS score, and shorter hospital stay than patients in ORP group (P<0.05). Major complications (≥grade 3b) did not differ between both groups (P=0.121). Positive surgical margins were 28.8% and 24.8% in ORP and RS-RARP, respectively (P=0.494). The BCR free-survival rates in ORP and RS-RARP at 1-year was 87.3% and 92.3%, respectively (Log-rank, P=0.740). At 1-, 6-, and 12-month after surgery, 42.4%, 79.7%, and 84.7% of men undergoing ORP were continent, compared with 72.8%, 90.4%, and 92% undergoing RS-RARP, respectively. Men in RS-RARP group achieved faster recovery of urinary continence compared to men in ORP group (Log-rank, P=0.001). CONCLUSIONS: RS-RARP had better perioperative outcomes and faster recovery of urinary continence compared with ORP. Short-term oncological outcomes were comparable between both surgical approaches.

Validity of a sponge trainer as a simple training model for percutaneous renal access.

OBJECTIVE: To evaluate the efficacy of our simply designed trainer for junior urologists to acquire the initial skills for percutaneous renal access (PRA). SUBJECTS AND METHODS: Three sponge sheets (60 × 50 × 10 cm) were arranged horizontally over each other. A rectangular groove was made in the middle sheet to accommodate an inflated balloon of a Foley catheter, radio-opaque metal balls, metal rings, or a plastic tube that were sequentially placed for the four training tasks. In each session, 18 trainees were asked to pass a fluoroscopically guided puncture needle from a surface point to the placed object in middle sheet. Clinical impact of training was evaluated by an experience survey on a 5-piont Likert scale (for model usefulness, tactile and fluoroscopic-guidance feedback) and success rate in further mentored practice. RESULTS: There was a gradual increase in tasks' and sessions' scores over the training sessions. According to the experience survey after first clinical practice, the mean (SD) score for overall model usefulness by trainees was 3.8 (0.9) with high fluoroscopic guidance reality [3.6 (1.1)] but poor tactile realism [2.3 (0.9)]. On mentored PRA, the success rate for trainees was 78.3%. CONCLUSION: Our early evaluation showed our novel, cost-effective and reproducible sponge trainer could be an effective training model for PRA with a beneficial impact on subsequent clinical practice.

Levels of Schistosoma mansoni Circulating Antigen in Chronic Hepatitis C Patients with Different Stages of Liver Fibrosis.

The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (µg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 µg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease.

Structure and applications of metal-organic framework based on cyanide and 3,5-dichloropyridine.

The reaction of the aqueous/acetonitrile solutions of K3[Cu(CN)4] and 3,5-dichloropyridine (3,5-dClpy), in the presence of Me3SnCl affords a new metal-organic framework (MOF), (3)∞[(CuCN)2·(3,5-dClpy)2], 1. The structure of the MOF 1 was characterized by IR, UV-visible, TGA and X-ray single crystal analysis. The structure of MOF 1 consists of CuCN building blocks which are connected by CN group forming 1D-zig-zag chains. Each chain is bridged to another chain by hydrogen bonding organizing 2D-sheets. The structure of 1 is further close packed by hydrogen bonds, π-π stacking and lp-π interactions creating 3D-network. The emission spectra and the thermodynamic parameters from TGA of the MOF 1 were discussed. The MOF 1 was used as heterogeneous catalyst for the oxidative discoloration of methylene blue dye (MB) by dilute solution of hydrogen peroxide as oxidant. The in vitro cytotoxic activity has been evaluated against the human breast cancer cell lines MCF-7. The cytotoxic effect of the MOF 1 on the viability of MCF-7 cells was determined by MTT assay.

On-demand use of tramadol, sildenafil, paroxetine and local anaesthetics for the management of premature ejaculation: A randomised placebo-controlled clinical trial.

OBJECTIVES: To compare the clinical efficacy of the on-demand use of four drugs in the management of patients with premature ejaculation (PE), as the off-label use of selective serotonin-reuptake inhibitors and topical penile anaesthetics is frequently indicated for the management of patients with PE, and tramadol HCl and sildenafil citrate were also tried for managing this disorder, but with recommendations based on weak evidence. PATIENTS AND METHODS: This was a single-centre, single-blind, placebo-controlled clinical trial conducted on 150 patients who had PE for >1 year. Patients were randomised equally into five groups. On-demand tramadol, sildenafil, paroxetine, local lidocaine gel or placebo was given for patients in groups 1-5, respectively. During the month before treatment, the intravaginal ejaculation latency time (IELT) and sexual satisfaction scores (on a 0-5-point scale) were measured and compared to the mean IELT and sexual satisfaction scores recorded during 4 weeks of on-demand drug administration, with monitoring of any possible side-effects. RESULTS: Tramadol-treated patients had a significantly longer mean (SD) IELT, of 351 (119) s, than the other groups. Local anaesthetic was significantly better than paroxetine in prolonging the IELT, at 278 (111) vs. 186 (65) s, respectively. The improvement in sexual satisfaction was significantly better in the sildenafil group, with a mean (SD) improvement of 2.9 (1) points, than in the paroxetine and local anaesthetic groups, at 2.2 (0.9) and 1.9 (0.9) points, respectively. CONCLUSIONS: The four drugs significantly improved IELT values over placebo. Tramadol was associated with significantly longer IELT values, whilst sildenafil induced significantly better sexual satisfaction than the other drugs. The four drugs had tolerable side-effects.

Role of combined use of potassium citrate and tamsulosin in the management of uric acid distal ureteral calculi.

In this article, we investigated the effect of the combined use of tamsulosin and potassium citrate (Uralyt-U(®)) for the treatment of uric acid stones in the distal ureter. The study was designed as a prospective, double blind randomized controlled trial. A total of 191 adult patients with radiolucent distal ureteral calculi were recruited. We included patients with solitary stones ≥5 mm with mild or moderate hydronephrosis and a normal contralateral tract. The patients were randomized into four equal groups (the placebo, tamsulosin, Uralyt-U(®), and the combined treatment groups). The patients were treated for a maximum duration of 4 weeks or until stone expulsion. The stone size in all groups ranged from 5 to 11 mm (7.69 ± 1.7 mm). The total expulsion rate of the stones was significantly lower in the control group (26.1%) compared with that of any of the other three groups (68.8, 58.7, and 84.8% respectively) (P < 0.05). Meanwhile, the difference between the Uralyt-U(®) group and the combined treatment group was also statistically significant (P < 0.05). When we studied the patients with stones >8 mm as a separate subgroup to find the effect of the used drugs on the relatively large stones, we detected that the expulsion rate of these stones was significantly higher in the patients who received the combined treatment in comparison with any of the other three groups (P < 0.05). In conclusion, the use of urinary alkalization with tamsulosin can increase the frequency of spontaneous passage of distal ureteral uric acid stones especially those of 8-11 mm.

Assessment of matrix metalloproteinase-1 for marking liver cirrhosis in chronic hepatitis C patients.

Our objective in the present study was to observe the change in the serum MMP-1 concentration using ELISA in 129 chronic hepatitis C (CHC) (78 non-cirrhotic and 51 with cirrhotic liver) and 50 healthy controls. The values of MMP-1 concentration increased in patients with CHC according to the stage of liver fibrosis. An area under the ROC curves (AUC) of the MMP-1 was 0.98 for discriminating patients with cirrhotic liver from healthy individuals and was 0.78 for discriminating patients with cirrhotic liver from non cirrhotic patients. The diagnostic potential of MMP-1 for discriminating cirrhosis from healthy individuals was very high with 98% sensitivity and 97% efficiency. MMP-1 detected cirrhosis in CHC with 71% sensitivity and 73% efficiency. In Conclusion, measurement of serum MMP-1 is useful for diagnosing liver cirrhosis in CHC patients.