Synthesis of water soluble copper(II) complexes: crystal structures,DNA binding,oxidative DNA cleavage,and in vitro anticancer studies

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H₂O (1) and [Cu(Thr)(Phen)H₂O]Cl·2H₂O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K _b) of (1) and (2) were 0.5 and 4.4 × 10⁵ M^?1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H₂O₂. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.     

A system dynamics model for national drug policy

Background

Data modeling techniques can create a virtual world to analyze decision systems. National drug authorities can use such techniques to take care of their deficiencies in decision making processes. This study was designed to build a system dynamics model to simulate the effects of market mix variables (5 P’s) on the national drug policy (NDP) indicators including availability, affordability, quality, and rationality. This was aimed to investigate how to increase the rationality of decision making, evaluate different alternatives, reduce the costs and identify the system obstacles.System dynamics is a computer-based approach for analyzing and designing complex systems over time. In this study the cognitive casualty map was developed to make a concept about the system then the stock-flow model was set up based on the market demand and supply concept.

Results

The model demonstrates the interdependencies between the NDP variables through four cognitive maps. Some issues in availability, willingness to pay, rational use and quality of medicines are pointed in the model. The stock-flow diagram shows how the demand for a medicine is formed and how it is responded through NDP objectives. The effects of changing variables on the other NDP variables can be studied after running the stock-flow model.

Conclusion

The model can initiate a fundamental structure for analyzing NDP. The conceptual model made a cognitive map to show many causes’ and effects’ trees and reveals some relations between NDP variables that are usually forgotten in the medicines affairs. The model also provides an opportunity to be expanded with more details on a specific disease for better policy making about medication.     

In Vitro Inhibitory Effect of Berberis vulgaris (Berberidaceae) and Its Main Component,Berberine against Different Leishmania Species

Background

Leishmaniasis has been identified as a major public health problem in tropical and sub-tropical countries. The present study was aimed to investigate antileishmanial effects of various extracts of Berberis vulgaris also its active compoenent, berberine against Leishmania tropica and L. infantum species on in vitro experiments.

Methods

In this study in vitro antileishmanial activity of various extracts of B. vulgaris also its active compoenent, berberine against promastigote and amastigote stages of L. tropica and L. infantum was evaluated, using MTT assay and in a macrophage model, respectively. Furthermore, infectivity rate and cytotoxicity effects of B. vulgaris and berberine in murine macrophage cells were investigated.

Results

The findings of optical density (OD) and IC₅₀ indicated that B. vulgaris particulary berberine significantly (P<0.05) inhibited the growth rate of promastigote stage of L.tropica and L.infantum in comparison to meglumine antimoniate (MA). In addition, B. vulgaris and berberine significantly (P<0.05) decreased the mean number of amastigotes in each macrophage as compared with positive control. In the evaluation of cytotoxicity effects, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages. Results also showed that when parasites were pre-incubated with B. vulgaris their ability to infect murine macrophages was significantly decreased.

Conclusion

B.vulgaris particularly berberine exhibited potent in vitro leishmanicidal effects against L. tropica and L.infantum. Further works are required to evaluate the antileishmanial effects of B.vulgaris on Leishmania species using clinical settings.     

Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort

Background and study aimTherapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM.Patients and methodsThis was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured.ResultsA total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn’s disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM.ConclusionsPatients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.     

Cor triatriatum dexter: antemortem diagnosis in an adult by cross sectional echocardiography.

Cor triatriatum dexter is a rare cardiac abnormality in which the right atrium is subdivided into two distinct chambers. This anomaly is generally attributed to the persistence of the right sinus venosus valve and it is frequently associated with severe malformations of other right heart structures. The antemortem diagnosis of the membrane may be difficult and its presence is often only established at necropsy. In a woman of 56 with Ebstein's anomaly the echocardiographic features of cor triatriatum dexter were examined before and during cardiac catheterisation. These investigations showed the position of the membrane, that there was no gradient between the two atrial chambers, and that there were perforations in the centre of the membrane.     

Optimal target temperature for slow pathway ablation in patients with atrioventricular nodal reentrant tachycardia

Objective To define optimal target temperature for the slow pathway ablation.Materials and methods In this study, 268 patients with atrioventricular nodal reentrant tachycardia (190 females; mean age, 49 ± 14 years) who underwent slow pathway ablation using a combined electroanatomic approach were enrolled. The patients were categorized into Group 1 if target temperature was <55°C or into Group 2 if target temperature was ≥55°C. Group 2 was divided into three subgroups of 55°C (Sgp-1), 60°C (Sgp-2), and 65°C (Sgp-3).Results Acute success rate was similar in both groups (P = 0.83). The ablation time (26.2 ± 20 vs. 36.5 ± 28 min; P = 0.014), fluoroscopy time (11.6 ± 9.7 vs. 17.8 ± 16.6 min; P = 0.035), and number of applications (4.1 ± 3.2 vs. 9.1 ± 6.5; P = 0.02) were lower for Group 2 than Group 1 patients. The frequency of AV or VA block, impedance rise, and coagulum formation were comparable in two groups (all P > 0.05). During mean follow-up of 14 ± 3 months, recurrence of the arrhythmia was seen in higher proportion of Group 1 than Group 2 patients (P = 0.036). Among the Group 2 patients, there were no significant differences between the three subgroups in terms of acute success rate, fluoroscopy time, risks of AV and VA block, pericardial effusion, and recurrence (All P > 0.05). Number of applications and RF pulse duration were lower in Sgp-2 and 3 compared to Sgp-1 (All P > 0.05). Impedance rise and coagulum formation were slightly higher in Sgp-3 compared to Sgp-1 and 2 but this difference did not reach statistical significance (All P > 0.05).Conclusions Compared to less than 55°C, target temperatures ≥55°C during slow pathway ablation significantly reduces fluoroscopy time, RF pulse duration, number of RF applications, and recurrence of AVNRT without increase in risk of AV or VA block or coagulum formation.     

Giving IV and oral amiodarone perioperatively for the prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass surgery: the GAP study

PURPOSES: We studied the use of perioperative IV and oral administration of amiodarone for the prevention of postoperative atrial fibrillation in patients undergoing coronary artery bypass graft surgery (CABG). BACKGROUND: In the United States, > 500,000 patients undergo CABG each year. Numerous studies to date have suggested that postoperative atrial fibrillation occurs in 30 to 50% of patients, leading to significant morbidity, including hypotension, heart failure, thromboembolic complications, prolonged hospital stay, and increased hospital costs. The objective of this study was to assess the use of IV amiodarone in combination with oral amiodarone to reduce the incidence of postoperative atrial fibrillation. METHOD: From January 1999 to October 1999, 51 patients scheduled for CABG were randomly selected for participation in the amiodarone administration trial. IV amiodarone, 0.73 mg/min, was administered on call to the operating room for 48 h, followed by oral amiodarone, 400 mg q12h, for the next 3 days. The amiodarone group was case-control matched to the incidence of postoperative atrial fibrillation in 92 patients undergoing CABG using conventional medical therapy during the same period. The primary end point of this study was the incidence of postoperative atrial fibrillation, length of hospital stay, and hospital costs, compared to the control group undergoing CABG during the same time. RESULTS: Atrial fibrillation occurred in 3 of 51 patients (5.88%) in the amiodarone group, compared to 24 of 92 patients (26.08%) in the control group. Length of hospital stay in the amiodarone group was less than in the control group (5.3 days vs 6.7 days), with a trend toward decrease in hospital costs. CONCLUSION: The administration of IV amiodarone in conjunction with oral amiodarone for a total dose of 4,500 mg over 5 days appears to be a hemodynamically well-tolerated, safe, and effective treatment in decreasing the incidence of postoperative atrial fibrillation, shortening length of stay, and a trend toward lowering hospital costs, even in patients with significantly reduced left ventricular function (< 30%). A large multicenter study using IV and oral amiodarone should be pursued prior to deciding whether its use should become standard therapy in all patients undergoing CABG in order to decrease the incidence of postoperative atrial fibrillation.     

Prevalence of pregnancy experiences and contraceptive knowledge among single adults in a low socio-economic suburban community in Kuala Lumpur,Malaysia

Background

This study aimed to investigate the prevalence of pregnancy experience and its association with contraceptive knowledge among single adults in a low socio-economic suburban community in Kuala Lumpur, Malaysia.

Methods

A cross-sectional survey was conducted in 2012 among the Kerinchi suburban community. Of the total 3,716 individuals surveyed, young single adults between 18 and 35 years old were questioned with regard to their experience with unplanned pregnancy before marriage. Contraceptive knowledge was assessed by a series of questions on identification of method types and the affectivity of condoms for the prevention of sexually transmitted diseases.

Results

A total of 226 female and 257 male participants completed the survey. In total, eight female (3.5%) participants reported experience with an unplanned pregnancy before marriage, and five male (1.9 %) participants had the experience of impregnating their partners. The participants had a mean total score of 3.15 (SD = 1.55) for contraceptive knowledge out of a possible maximum score of five. Female participants who had experienced an unplanned pregnancy had a significantly lower contraceptive knowledge score (2.10 ± 1.48) than who had never experienced pregnancy (3.30 ± 1.35), p<0.05. Likewise, male participants who had experienced impregnating their partners had a significantly lower contraceptive knowledge score (1.60 ± 1.50) than those who did not have such experience (3.02 ± 1.59), p<0.05.

Conclusion

The results showed evidence of premarital unplanned pregnancy among this suburban community. The low level of contraceptive knowledge found in this study indicates the need for educational strategies designed to improve contraceptive knowledge.