Structural Development of Self Nano Emulsifying Drug Delivery Systems (SNEDDS) During <Emphasis Type="BoldItalic">In Vitro</Emphasis> Lipid Digestion Monitored by Small-angle X-ray Scattering

Purpose To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. Materials and Methods Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. Results The data revealed that a lamellar phase forms immediately after initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The change of the relative amounts of these phases clearly demonstrates that lipolysis is a dynamic process. The formation of these phases is driven by the lipase which continuously hydrolyzes triglycerides from the oil-cores of the nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose that this change of the over-all composition of the intestinal fluid with increased fraction of hydrolyzed nanoemulsion induces a change in the composition and effective critical packing parameter of the amphiphilic molecules, which determines the phase behavior of the system. Control experiments (only the digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of the SNEDDS formulation. Conclusions The current results demonstrate that SAXS measurements combined with the in vitro dynamic lipolysis model may be used to elucidate the processes encountered during the digestion of lipid-based formulations of poorly soluble drugs for oral drug delivery. Thus the combined methods may act as an efficient screening tool.     

Paper stamp checklist tool enhances asthma guidelines knowledge and implementation by primary care physicians

BACKGROUND:

The Canadian Clinical Practice Guidelines (CPGs) for the management of asthmatic patients were last published in 1999, with updates in 2001 and June 2004. Large disparities exist in the implementation of these guidelines into clinical practice.

OBJECTIVE:

The present study evaluated the knowlege of Quebec-based primary care physicians regarding the CPGs, as well as patient outcomes before and after introducing physicians to a new clinical tool – a memory aid in the form of a self-inking paper stamp checklist summarizing CPG criteria and guidelines for assessing asthmatic patient control and therapy. The primary objective of the present study was to assess whether the stamp would improve physicians’ knowledge of the CPGs, and as a secondary objective, to assess whether it would decrease patient emergency room visits and hospitalizations.

METHODS:

A prospective, randomized, controlled study of 104 primary care physicians located in four Quebec regions was conducted. Each physician initially responded to questions on their knowledge of the CPGs, and was then randomly assigned to one of four groups that received information about the CPGs while implementing an intervention (the stamp tool) aimed at supporting their decision-making process at the point of care. Six months later, the physicians were retested, and patient outcomes for approximately one year were obtained from the Régie de l’assurance maladie du Québec.

RESULTS:

The stamp significantly improved physicians’ knowledge of the CPGs in all Quebec regions tested, and reduced emergency room visits and hospitalizations in patients who were followed for at least one year.

CONCLUSION:

A paper stamp summarizing CPGs for asthma can be used effectively to increase the knowledge of physicians and to positively affect patient outcomes.     

Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

AIM： To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome （IBS） patients and healthy subjects using molecular-based techniques.
METHODS： Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization （FISH） and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction.
RESULTS： The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria （4.2 ± 1.3 vs 8.3 ± 1.9, P 〈 0.01） in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower （6 ± 0.6 vs 19 ± 2.5, P 〈 0.001） in the IBS patients in both fecal and duodenal brush samples than in healthy subjects.
CONCLUSION： Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.     

Hyperplastic polyps and the risk of adenoma recurrence in the polyp prevention trial

BACKGROUND AND AIMS: Recent studies have suggested that some hyperplastic polyps may be associated with an increased risk of colorectal cancer. Prospective information on the risk of adenoma recurrence associated with hyperplastic polyps is limited. We sought to investigate whether the coexistence of hyperplastic polyps with adenomas increases the risk of adenoma recurrence. METHODS: We used unconditional logistic regression models to examine the association between baseline hyperplastic polyps and subsequent adenoma recurrence during a 3-year follow-up evaluation, among 1637 participants in the Polyp Prevention Trial. RESULTS: A total of 437 participants (26.7%) had hyperplastic polyps coexisting with adenomas at baseline. Of these, 132 (30.2%) had at least one hyperplastic polyp in the proximal colon, whereas 305 (69.8%) had only distal hyperplastic polyps. When compared with subjects without any hyperplastic polyps at baseline, there was no statistically significant association between the presence of baseline hyperplastic polyps and recurrence of any adenoma (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.94-1.51) or advanced adenoma (OR, 1.25; 95% CI, 0.78-2.03). Also, there was no association between hyperplastic polyp location and adenoma recurrence (OR, 1.01; 95% CI, 0.69-1.48) for any proximal hyperplastic polyp (OR, 1.26; 95% CI, 0.96-1.65) and for distal hyperplastic polyps. CONCLUSIONS: The coexistence of hyperplastic polyps with adenomas, irrespective of location, does not confer an increased risk of adenoma recurrence beyond that of adenomas alone within 3 years of follow-up evaluation. Prospective long-term studies on adenoma recurrence risk associated with hyperplastic polyps in screening populations are needed.     

Bessere Prognose mit kontinuierlicher HER2-Blockade HER2-positives Mammakarzinom

Die gegen den humanen epidermalen Wachstumsfaktorrezeptor 2 (HER2) gerichtete Therapie hat auch in der metastasierten Situation die Prognose bei HER2-positivem Mammakarzinom deutlich verbessert. überlebenszeiten von gut zehn Jahren ab Diagnose „metastasiertes, HER2-positives Mammakarzinom“ sind mit der kontinuierlichen HER2-Blockade keine Seltenheit mehr.     

Gemcitabine-based induction chemotherapy and concurrent with radiation in advanced head and neck cancer

To evaluate the efficacy and toxicity of gemcitabine-based induction chemotherapy followed by concurrent gemcitabine and radiotherapy in advanced squamous cell carcinoma of head and neck. A total of 28 patients with locally advanced squamous cell carcinoma of the head and neck were enrolled. All patients were treated with 2 cycles of induction gemcitabine 1?gm/m² on days1 and 8 plus cisplatin 75?mg/m²no day 1 of a 3-week cycles followed by conventionally fractionated radiotherapy to 70?Gy in 35 fractions concurrent with weekly gemcitabine 100?mg/m² within 2?h before radiotherapy. Median age was 56.5?years (range, 30?C68). Four patients (14.3?%) achieved complete response (CR) and 19 patients (67.9?%) had partial response (PR) after induction chemotherapy. After concurrent chemo-radiotherapy, we reported 17 (60.7?%) CR and 8 (28.6?%) PR. Median loco-regional recurrence-free survival, progression-free survival, and overall survival were 17, 12.5, and 21?months, respectively. Performance status, T stage, AJCC stage, and response to chemo-radiation were found to have significant impact on survival. Acute grade 3 toxicity of concurrent chemo-radiation included 35.7?% dysphagia, 25?% stomatitis, and 10.7?% neutropenia, whereas late grade 3 toxicity included xerostomia in 7.1?% and stomatitis in 3.6?% of patients. Gemcitabine-based induction and concurrent chemo-radiotherapy is effective treatment for locally advanced squamous cell carcinoma of head and neck with acceptable and manageable toxicity. Optimizing dose and schedule of gemcitabine-based chemo-radiation is still needed.     

Comparative study on preparative methods of DC-Chol/DOPE liposomes and formulation optimization by determining encapsulation efficiency

Three most commonly used preparative methods, dry-film, reverse phase evaporation and ethanol injection were employed to prepare cationic liposomes composed of DC-Chol and DOPE, respectively. The resulting samples were contrasted through morphology observation, particle size and zeta potential analysis. Sephadex filtration method with high selectivity was developed to determine the encapsulation efficiency of plasmid DNA-loaded cationic vectors, on this basis, cationic liposomes formulation was further optimized by applying Box Behnken design with encapsulation efficiency as evaluation index. The results showed that liposomes prepared by dry-film method were of best quality and stability, moreover, the optimum formulation of cationic liposomes and optimal value of each influencing factors were quantitatively obtained, measured value was highly consistent with predicted results. These findings preliminarily clarified the effect of preparative methods on performance of cationic liposome, as well as formulation factors on encapsulation efficiency, and will provide important methodological reference for further study of liposomes carriers for gene delivery.