Powder Compression Properties of Paracetamol,Paracetamol Hydrochloride,and Paracetamol Cocrystals and Coformers

The objective was to study the relationship between crystal structure, particle deformation properties, and tablet-forming ability for the monoclinic form of paracetamol (PRA), 2 cocrystals and a salt crystal of PRA in addition to 2 coformers (oxalic acid and 4,4′-bipyridine). Thus, the structure–property–performance relationship was investigated. Analytical powder compression was used for determination of effective plasticity, as inferred from the Heckel yield pressure and the Frenning parameter, and the elastic deformation was determined from in-die tablet elastic recovery. The plasticity could not be linked to the crystal lattice structure as crystals containing zig-zag layers displayed similar plasticity as crystals containing slip planes. In addition, crystals containing slip planes displayed both high and low plasticity. The mechanical properties could not be linked to the tablet-forming ability as the tablet tensile strength, unexpectedly, displayed a tendency to reduce with increased plasticity. Furthermore, the elastic deformation could not explain the tablet-forming ability. It was concluded that no relationship between structure–property–performance for PRA and its cocrystals and salt could be established. Thus, it was indicated that to establish such a relationship, an improved knowledge of crystallographic structure and interparticle bonding during compaction is needed.     

Design,synthesis and evaluation of alkylphosphocholine-gefitinib conjugates as multitarget anticancer agents

The evolving resistance to the currently used chemotherapeutic agents requires continuous efforts to develop new anticancer agents overcoming resistance and with lower side effects. Polypharmacology via designing a single molecule intercepting multiple signaling pathways is more effective than targeting a single one. Several alkylphosphocholines show anticancer activity via inhibition of Akt phosphorylation. On the other hand, several molecules having quinazoline scaffold elicit anticancer activity through inhibition of epidermal growth factor receptor (EGFR) tyrosine kinases. We report our efforts to develop alkylphosphocholines-gefitinib conjugates as multitarget anticancer agents. The antiproliferative activities of the newly synthesized compounds were evaluated against cell lines representing lung, breast, liver and skin cancers. In addition, the capability of the newly synthesized compounds to inhibit Akt phosphorylation and EGFR tyrosine kinases were determined. The results emphasized the influence of the linkers’ length on the elicited bioactivity. The long chain linkers possessing conjugates were more active regarding both of the elicited antiproliferative effect and inhibition of Akt phosphorylation, while maintained the ability to inhibit EGFR tyrosine kinases. Their cytotoxic activities were superior or comparable to erlotinib and miltefosine.     

Propoxur-induced oxidative DNA damage in human peripheral blood mononuclear cells: protective effects of curcumin and α-tocopherol

The present study enumerates the attenuating effects of curcumin and α-tocopherol against propoxur induced oxidative DNA damage in human peripheral blood mononuclear cells (PBMC). Cultured cells were isolated from peripheral blood of healthy volunteers, and were exposed to varying concentrations of propoxur (0–21?μg/ml) for 6, 12, and 24?h, and in combination with curcumin (9.2?μg/ml) or α-tocopherol (4.3?μg/ml) or both. Cytotoxic effect of propoxur was examined by MTT assay. The role of oxidative stress beneath the cytotoxicity of propoxur was evaluated by the measurement of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OH-dG) levels in cell lysate. A concentration-dependent cell death, depletion of GSH, an increase in the level of both MDA and 8-OH-dG were observed. Co-treatment with curcumin or α-tocopherol significantly attenuates depleted GSH, decrease in MDA and 8-OH-dG levels in propoxur exposed cells (p?相似文献   

Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci

Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1–8?µg/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections.     

Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11 , which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5 , 8 , and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8 , 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

     

Frequency and features of nocturnal enuresis in Pakistani children aged 5 to 16 years based on ICCS criteria: a multi-center cross-sectional study from Karachi,Pakistan

Background

Nocturnal enuresis (NE) is a common symptom in children worldwide. International Children’s Continence Society (ICCS) defines enuresis as either mono-symptomatic, NE with lower urinary tract symptoms and NE with co-morbid conditions. The objectives of this study were to determine the frequencies and types of NE and associated symptoms and conditions in children aged 5 to 16?years based on ICCS criteria.

Methods

A multi-center cross sectional study was conducted between November 2012 and December 2013 in the primary care clinics of four hospitals in Karachi. Children aged five to fifteen years were included through consecutive sampling. Informed consent was obtained from the parents and a pre-coded semi-structured questionnaire was used to obtain the information. Data was entered on SPSS version 20.0 and multivariable logistic regression analysis was used for data analysis.

Results

Out of 429 children aged between five and sixteen years, 243(56.9%) were boys and the remaining 186(43.1%) were girls. One hundred and eighty three children (43%) had nocturnal enuresis (NE). Forty four (10.3%), had mono-symptomatic NE, 57(31.1%) had associated lower urinary tract symptoms (NE-LUTS), whereas 30 (16.3%) had NE with a co-morbid condition. Fifty two (28.4%) NE’s had at least one of both LUTS and a co-morbid condition. Out of the 246(57%) non-enuretic’s, 31(12.6%) had a LUTS, 95(38.6%) had a co-morbid condition and 57(23.2%) had at least one of both LUTS and a co-morbid condition. The remaining 63 (25.6%) were symptom free. Increased voiding frequency, urgency, dysuria, suprapubic pain and daytime incontinence were the LUTS significantly associated with NE. Co-morbid conditions significantly associated with NE included constipation, congenital defects, developmental delay, and learning and sleep problems.

Conclusion

Although NE can be an only symptom, it is often associated with lower urinary tract symptoms like dysuria, urgency, suprapubic pain, and daytime incontinence. Children presenting with NE often have co-morbid conditions like constipation, urinary tract infection, sleep disorders, and developmental delay. Many children presenting with these conditions as the primary complaint may also have NE. It should be addressed as unrecognized and untreated NE can cause additional morbidity and distress.

     

Risk modeling of non-communicable diseases using socio-demographic characteristics,lifestyle and family disease history among university students in Bangladesh

Aim

The objective of this study was to determine risk factors for non-communicable diseases (NCDs) on the basis of socio-demographic characteristics, lifestyle-related determinants, environmental and psychological characteristics, and individual and family disease history among university students in Bangladesh.

Study design

Cross-sectional survey.

Methods

Using the WHO STEPwise approach for NCDs, a cross-sectional study was conducted among 1,140 students. The collected data were analyzed using the Statistical Package for Social Sciences (SPSS) software, version 22.

Results

In all, 29.2% of the respondents (BMI?≥?23.00 kg/m²) were overweight and/or obese, and almost two-thirds (65%) of them did not take part in any physical activity (PA). A third (33.3%, p?=?0.002) of male smokers reported health problems and it was found that environmental tobacco smoke (ETS) was significantly responsible for developing asthma (OR?=?0.55; CI?=?0.33–0.93). Individual and family history of NCDs was statistically significant for obesity and asthma and considerably increased the odds ratio for heart disease.

Conclusion

This study shows that the number of students suffering from different types of NCDs is not negligible. Their lifestyle and family history of NCDs are responsible for this to a significant extent. Urgent initiatives should be taken to rein in the spread of NCDs among the youth of Bangladesh.

     

Effect of training program regarding smoking cessation counseling for primary health care physicians in Port Said City,Egypt

Background

Smoking is a major risk factor for death-related diseases. Not all healthcare professionals are following evidence-based guidelines for smoking cessation counseling in primary care settings. The WHO, Framework Convention on Tobacco Control (FCTC), and United States Public Health Service (USPHS) guidelines recommend that all healthcare professionals, including students in healthcare training programs, receive education in the management of tobacco use and dependence.

Objective

To evaluate the effect of training programs for primary healthcare physicians on the knowledge, attitude, and practice of smoking cessation counseling.

Methods

This was a pre-post intervention study. The study included 74 primary care physicians working in primary healthcare centers affiliated with the Ministry of Health and Suez Canal University Hospitals in Port Said City. The study was conducted between June 2015 and March 2016 using a structured questionnaire and observation checklist to assess counseling of patients willing to quit smoking.

Results

There were highly statistically significant improvements in the physicians’ median scores of knowledge (30%–80%), attitude (65% -100%), and practice (20%–70%) (p?<?0.001) pre-post intervention. The most frequent correct knowledge was consequences of smoking (73%–87.3%) (p?<?0.001) pre-post intervention. The most favorable attitude was the importance of smoking cessation (70.3%–100%) (p?<?0.001) pre-post intervention. The best observed correct practice was asking about smoking (70.3%–100%) (p?<?0.001) pre-post intervention.

Conclusion

Knowledge, attitude, and practice skills regarding smoking cessation counseling among primary healthcare physicians were markedly improved after implementation of the education program.

     

PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization

The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze–thaw method. Response surface methodology with Box–Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze–thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12?hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze–thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.     

Effect of pharmacist care on medication adherence and cardiovascular outcomes among patients post-acute coronary syndrome: A systematic review

Background

The impact of collaborative and multidisciplinary health care on the outcomes of care in patients with acute coronary syndromes (ACS) is well-established in the literature. However, there is lack of high quality evidence on the role of pharmacist care in this setting.