Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both and . In addition, Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: an assessment on mechanism of drug release

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system

Cross-linked guar gum and sodium borate based microspheres as colon-targeted anticancer drug delivery systems for 5-fluorouracil

The aim was to prepare cross linked polymer of 5-fluorouracil loaded microspheres containing guar gum and sodium borate for colon-targeted drug delivery systems. Micro spheres were prepared using emulsification cross linking method. The influence of drug polymer ratio, cross linker agent concentrations and cross linking timing on in vitro drug release and characteristics in terms of drug loading, entrapment efficiency and yielding percentage were investigated. The optimum drug loading, entrapment efficiency and percent yield were obtained from formulations with the lowest content of cross linker agent over 2 h of cross linking timing but with the highest drug to polymer ratio 1:11. The optimum in vitro drug release was obvious upon decreasing drug to polymer ratio up to 1:09, resulting in 81.5% drug release over 24 h. In conclusion, micro spheres composed of gaur gum and sodium borate can delay and control the release of 5-fluorouracil over 24 h. Thus, further in vivo studies are suggested for final assessment

Causes of poor visual outcome after bilateral congenital/developmental cataract surgery in a teaching hospital, Lahore [Pakistan]

Objective: To determine the causes of poor visual outcome after bilateral congenital/ developmental cataract surgery, like posterior capsular opacification, strabismus, glaucoma, retinal detachment and endophthalmitis in a teaching hospital, Lahore Pakistan

Methods: This prospective study was conducted in Eye unit 1, Services Hospital, SIMS, Lahore from January,2010 to January, 2016. During this periodwe evaluated 80 eyes in 40 children aged 6 years to 12 years with bilateral congenital cataract with no other associated posterior segment pathology. Male children were 26 and female were 14 in number. Follow up period was for 6 years. A comprehensive detailed history, demographic data, surgical techniques and causes of poor visual outcome was noted like posterior capsular opacification, glaucoma, strabismus, retinal detachment and endophthalmitis

Results: The incidence of posterior capsular opacification was observed in 45%,glaucoma in 2.5%,strabismus in 12.5%. Retinal detachment and endophthalmitis was not observed in any child after bilateral congenital cataract surgery

Conclusion: The present study revealed that the early detection and treatment including refractive rehabilitation and regular and close follow-up are essential for good visual outcome. Better visual outcome can further be improved by parent's guidance and motivation postoperatively

Exertional dyspnea in patients with diabetes mellitus: evaluation by myocardial perfusion scintigraphy

Coronary Artery disease is a major cause of morbidity and mortality in patients with diabetes mellitus. They have high incidence of silent ischemia as pain perception is blunt in such patients. As a result many of them present with atypical symptoms like exertional dyspnea, instead of classical chest pain as their chief presenting complaint. We evaluated incidence of myocardial perfusion scintigraphic [MPS] evidence of coronary artery disease [CAD] in patients with type II diabetes mellitus without known CAD presenting with exertional dyspnea as chief presenting complaint. We conducted stress-redistribution SPECT MPS with intravenous injection of 93-130 MBq [2.5-3.5 mCi] 201T1-thallous chloride in 290 subjects with type II diabetes mellitus having exertional dyspnea [SOB] as study group [151 male and 139 female, age range 20 to 76 years]. 138 asymptomatic subjects with type II diabetes mellitus also underwent same procedure as control group [56 male and 82 female, age range 29 to 65 years]. Upon the bases of clinical history, study groups were further divided into three categories, Esob=exertional SOB [n=54], AcpD= atypical chest pain with dyspnea [n=114] and TcpD=typical chest pain with dyspnea [n=122]. We conducted visual analysis on reconstructed tomographic slices. CAD was present in 34.78% control [ischemia 23.91%, myocardial infarction 10.87%] and in 66.9% study group subjects [ischemia 49.31%, myocardial infarction 17.87%]. Incidence of CAD was high in Esob group than control [48.15% vs. 34.78%], AcpD group than Esob [64.91% vs. 48.15%] and TcpD group than AcpD [77.05% vs. 64.91%]. Stress induced ischemia [SII] was more frequent in Esob group than control [37.04% vs. 23.91%] and AcpD group than Esob [50% vs. 37.04%]. However, its occurrence was almost similar in TcpD and AcpD groups [54.1% vs. 50%]. Observed frequency of myocardial infarction was almost same in control [10.87%] and Esob [11.11%] group. Incidence of myocardial infarction was higher in AcpD group than control [14.91% vs. 10.87%] and TcpD group than AcpD [22.95% vs. 14.91%]. Our study concludes that incidence of myocardial ischemia and infarction is quite high in patients with type-II diabetes mellitus presenting with exertional dyspnea. Presence of chest pain further increases the likelihood of CAD in these patients. We should perform MPS in all patients with type II diabetes mellitus who present with exertional dyspnea, even if they have no chest pain

Outcome of cardiopulmonary resuscitation in hospital patients following heart attack

Background: The aim of this study was to evaluate in hospital survival of the patients admitted or presenting in cardiac emergency room with cardiac arrest as well as to look into the factors associated with success rate of CPR

Methods: Prospective study of consecutive 404 patients admitted in cardiac emergency room who received advance cardiac life support protocol after in-hospital cardiac arrest. Short term survival [Return of spontaneous respiration and circulation] and hospital survival at the time of discharge were measured. In addition, factors affecting the outcome of CPR age, gender, duration of CPR, associated arrhythmias, defibrillation and TPM implantation were also taken in account. Main outcome: Immediate survival after CPR, at 24 hours and at the time of discharge

Results: Overall 134 out of 404 patients [33%] who received advanced cardiopulmonary life support, survived to hospital discharge. Survival was better in male i.e. 37% versus 26% in female. Younger age group showed better survival i.e. 40.4% in age range of 30 to Department of Cardiology, Punjab Medical College, Allied Hospital Faisalabad. 49 years, 33% in 50 to 69 years and 28% in 70 years or older. Survival rate was 86% when CPR duration was less than 10 minutes, at 15 minutes 48% and at 20 minutes CPR time, 25% patients survived. Only 13.9% patients survived at CPR time of 30 minutes. Survival was 42% for patients with VF and 68% in those presenting with VT, 61% in fast AF with hemodynamic instability. 29% patients having TPM implantation survived of cardiac arrest. Poor survival in patients of cardiac arrest presenting with new development of LBBB i.e. 18%, best in inferior wall STEMI [32%], intermediate in anterior wall STEMI [28%]. Total of 40 patients in cardiogenic shock had cardiac arrest and 17.5% resuscitated successfully

Conclusion: Survival was highest for patients with primary cardiac arrest, with short CPR duration, young age, male gender and with tachyarrhythmia. Patients who experienced cardiac arrest at cardiac emergency room have better survival. Survival was poor in patients with cardiogenic shocks, CPR duration more than 20 minutes

Hepatitis A - frequency in children with non-specific abdominal symptoms

To study the frequency of subclinical hepatitis 'A' in children having non-specific abdominal symptoms. Design: A descriptive study. Place and Duration of Study: This study was conducted at Combined Military Hospital [CMH], Peshawar from June to December 2000. Subjects and Three hundred and sixty children of either gender, < 12 years of age, presenting with vague abdominal symptoms and no jaundice were evaluated for hepatitis. Eighty eight [24.4%] children meeting the inclusion criteria of elevated serum alanine aminotransferase [ALT], twice the upper limits of normal [90 IU/L], and normal serum bilirubin were labelled as subclinical hepatitis. A total of 360 children were evaluated for vague abdominal symptoms and 96 [26.7%] of them had hepatitis on laboratory profile. Eight patients developed early jaundice and were excluded from the study. Out of 88 [24.4%] cases of subclinical hepatitis, 82 [93.2%] had hepatitis-A, 03 [3.4%] had hepatitis-B, while no causative agent was found in 03 [3.4%] children. The common presenting symptoms were abdominal pain/discomfort, loss of appetite, nausea, vomiting, malaise, fatigue and fever. Hepatomegaly and splenomegaly was documented in 56% and 43% cases respectively. A history of exposure to a patient with hepatitis was present in 14/88 [15.9%] cases whereas no child was vaccinated against HAV. Serum ALT level declined to normal limits within 4 weeks for 77/88 [87.5%] cases and within 6 weeks for 84/88 [95.4%]. All cases recovered spontaneously with out any complication. Hepatitis-A was rampant in children presenting with vague abdominal symptoms in our series