Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.     

Determinants of life satisfaction among stroke survivors 1 year post stroke

Stroke is the major leading cause of death and severe long-term disability worldwide. The consequences of stroke, aside from diminished survival, have a significant impact on an individual''s capability in maintaining self-autonomy and life satisfaction (LS). Thus, this study aimed to assess LS and other specific domains of LS in stroke survivors following their first-ever stroke, and to describe the relationship using socio-demographic and stroke-related variables.This study recruited 376 stroke survivors (244 men and 132 women, mean age: 57 years) 1 year following stroke. Data on participants’ LS (measured using the Life Satisfaction Questionnaire [LiSat-11]), socio-demographics, and stroke-related variables were collected.Univariate analysis showed that LS and the 10 specific domains were not associated with the patients’ gender or stroke type; however, age at onset, marital status, and vocational situation were significantly associated with some domains in LiSat-11 (Spearman''s rho = 0.42–0.87; all P < 0.05). Logistic regression revealed that verbal and cognitive dysfunction were the most negative predictors of LS (odds ratio 4.1 and 3.7, respectively).LS is negatively affected in stroke survivors 1 year post onset. The results indicate that recovering social engagement is a positive predictor of higher LS in stroke survivors. More importantly, the findings revealed that cognitive and verbal dysfunctions were the most prominent negative predictors of the overall gross level of LS. Multidisciplinary rehabilitation for stroke survivors is therefore critical.     

Human papillomavirus subtype 16 is common in Pakistani women with cervical carcinoma.

INTRODUCTION: Human papillomavirus (HPV) is recognized as a major causative agent for cervical carcinomas. Based on their oncogenic potential, HPV subtypes have been divided into high- and low-risk. In Pakistan, screening for HPV in female patients is not commonly practiced, and as a consequence, the degree of HPV prevalence and its correlation with cervical cancer is unknown. OBJECTIVE: In this study, we have attempted to estimate the prevalence of HPV infection, and also the HPV subtype profile, among Pakistani women with cervical cancer from varied geographical, racial, and social backgrounds within Pakistan. METHODOLOGY: Women visiting two tertiary care hospitals in Karachi, diagnosed with carcinoma of the cervix within the past 15 years, were analyzed for HPV subtypes in their cancer specimens. Retrospectively, 60 paraffin-embedded cervical cancer biopsies were examined for the presence of HPV DNA. After DNA extraction from these samples, polymerase chain reaction (PCR) was used to amplify the HPV L1 gene using the consensus (general) primers, and primers specific for subtypes 16 and 18. RESULTS: Of the 60 samples analyzed, only one sample was HPV negative; the rest of the samples were positive for the presence of HPV. Of the 59 HPV positive samples, 56 showed the presence of HPV16 and one sample was positive for HPV18; HPV subtype could not be determined in two samples. CONCLUSION: Our results show a strong relationship between HPV infection and cervical cancer among Pakistani women. These results underscore the need to implement regular HPV screening for Pakistani women. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.     

Acute pancreatitis during sickle cell vaso-occlusive painful crisis

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.     

Management of tandem occlusions in patients who receive rtPA

Journal of Thrombosis and Thrombolysis - Tandem occlusions exist in 17–32% of large vessel occlusion (LVO) strokes. A significant concern is bleeding when carotid stenting is performed in...     

Comprehensive approach to cardiac amyloidosis care: considerations in starting an amyloidosis program

Heart Failure Reviews - Amyloidosis is a multisystem disease which continues to present in later stages due to delayed diagnosis. Once the disease is identified, the coordination of ongoing care...     

Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX study.

The Medical Patients with Enoxaparin (MEDENOX) trial was a randomized, placebo-controlled study that defined the risk of venous thromboembolism (VTE) in acutely ill, immobilized, general medical patients and the efficacy of the low-molecular-weight heparin, enoxaparin, in preventing thrombosis. We performed a post-hoc analysis to evaluate the effect of 40 mg enoxaparin once daily on MEDENOX patient outcome in different types of acute medical illness (heart failure, respiratory failure, infection, rheumatic disorder and inflammatory bowel disease) and pre-defined risk factors (chronic heart and chronic respiratory failure, age, immobility, previous VTE and cancer). The primary outcome was the occurrence of documented VTE between days 1 and 14. The relative risk reduction [95% confidence intervals (CI)] for VTE comparing 40 mg enoxaparin with placebo in the subgroups were: acute heart failure, 0.29 (95% CI, 0.10-0.84); acute respiratory failure, 0.25 (95% CI, 0.10-0.65); acute infectious disease, 0.28 (95% CI, 0.09-0.81); and acute rheumatic disorder, 0.48 (95% CI, 0.11-2.16). The relative risk reduction for VTE in the pre-defined risk factor subgroups were: chronic heart failure, 0.26 (95% CI, 0.08-0.92); chronic respiratory failure, 0.26 (95% CI, 0.10-0.68); age, 0.22 (95% CI, 0.09-0.51); immobility, 0.53 (95% CI, 0.14-1.72); previous VTE, 0.49 (95% CI, 0.15-1.68); and cancer, 0.50 (95%o CI, 0.14-1.72). The beneficial effects of enoxaparin extend to a wide range of acutely ill medical patients.     

Prevalent phenotypes and antibiotic resistance in Escherichia coli and Klebsiella pneumoniae at an Indian tertiary care hospital: plasmid-mediated cefoxitin resistance.

BACKGROUND: The beta-lactam antibiotics, in combination with aminoglycosides, are among the most widely prescribed antibiotics. However, because of extensive and unnecessary use, resistance to these drugs continues to increase. In recent years, resistance in the Indian bacterial population has increased markedly, the majority showing complex mechanisms. Due to increased transcontinental movement of the human population, it would be wise to know the prevalence and resistance complexity of these strains, well in advance, in order to formulate a policy for empirical therapy. METHODS: One hundred and eighty-one isolates of Escherichia coli and 61 isolates of Klebsiella pneumoniae obtained from 2655 non-repeat samples of pus (912) and urine (1743) were studied, and their resistance rates and patterns were noted. The isolates were analyzed for prevalent aminoglycoside and cephalosporin resistance phenotypes and for the presence of extended spectrum beta-lactamase (ESBL) and AmpC enzymes by spot-inoculation and modified three-dimensional tests developed in our laboratory. Fourteen isolates of E. coli and six of K. pneumoniae, resistant to all of the antibiotics tested, were selected for plasmid screening, curing, and transconjugation experiments, and for comparative evaluation of the double disk synergy test (DDST) and modified three-dimensional test (TDT) for detection of beta-lactamases. RESULTS: Urinary E. coli isolates showed maximum susceptibility to amikacin (57.1%), followed by tobramycin (38.5%) and gentamicin (31.9%). Eighteen (19.8%) isolates were susceptible to cefotaxime, whereas 11 (12.1%) were susceptible to ceftriaxone. The K. pneumoniae isolates from urine samples showed maximum susceptibility to tobramycin (63.6%) followed by amikacin (54.5%). Of the K. pneumoniae isolates, 31.8% were susceptible to cefotaxime and 13.6% were susceptible to ceftriaxone. A more or less similar trend of antibiotic susceptibility was noted in E. coli and K. pneumoniae isolates from pus samples. Twenty-six (14.4%) E. coli and 15 (24.6%) K. pneumoniae isolates were found to be ESBL-producers by NCCLS-ESBL phenotypic confirmatory test. Eighteen (9.9%) E. coli and 19 (31.1%) K. pneumoniae isolates were found to be AmpC enzyme-producers by our modified TDT. The simultaneous occurrence of ESBL and AmpC enzymes was noted in 7.7% and 9.8% isolates of E. coli and K. pneumoniae, respectively. CONCLUSIONS: The prevalence of multidrug-resistant bacterial isolates is quite high in our bacterial population. On comparative evaluation of DDST and TDT in resistant isolates, TDT was found to be the better method, detecting ESBLs in 80% of isolates compared to 15% with DDST. A 19.9-kb plasmid was consistently present in all the screened isolates of E. coli and K. pneumoniae, and was inferred to encode cefoxitin and tetracycline resistance based on curing and transconjugation experiments.