25 research outputs found
In vitro assessment of alkylglycosides as permeability enhancers
A series of alkylglycosides has been evaluated on human cell lines to determine its ability to open cellular tight junctions. Alkylglycosides were applied to cell monolayers; the resulting change in resistance was determined by transepithelial electrical resistance measurements. Change in resistance across cell monolayers is an indieation of tight junction activation, whereas subsequent increase in resistance signifies monolayer recovery. Of the 13 alkylglycosides tested, 4 caused irreversible solubilization of cell membranes, 5 allowed a partial recovery of the monolayer after a relatively rapid reduction in resistance, and 4 induced a decrease in resistance with more complete cell recovery. Alkylglycosides allowing extensive cell recovery after removal may indieate tight junctions activity dominance over membrane fluidity Repeated application of alkylglycosides for 6 hours lowered resistance across cells, which returned to near-normal values after a recovery period of 48 hours. A model dye was transported across the cell monolayer only in the presence of an alkylglycoside, although recovery of cells was incomplete. Activity of the alkylglycosides was unrelated to either the carbon chain length or to the carbohydrate moiety. A direct correlation was established between the concentration of applied alkylglycoside and reduction in resistance over a constant time period. Dodecylmaltoside and oetylglucoside were found to be optimal in decreasing resistance at low concentrations and allowing significant recovery of cells. Therefore these 2 alkylglycosides may be useful in facilitating drug transport across biological membranes
The Effects of Dodecyl Maltoside and Sodium Dodecyl Sulfate Surfactants on the Stability and Aggregation of Recombinant Interferon Beta-1b
A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10 mg plus permeation enhancer DDM, for the acute treatment of episodic migraine
BACKGROUND: DFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms. METHODS: This was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months. RESULTS: A total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period. CONCLUSION: DFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely
Effects of cysteine and diethylmaleate pretreatments on renal function and response to a nephrotoxicant
Association between endocrine pancreas and ductal system. More than an epiphenomenon of endocrine differentiation and development?
2sireservedTraditional histological descriptions of the pancreas distinguish between the exocrine and the endocrine pancreas, as if they were two functionally distinct glands. This view has been proven incorrect and can be considered obsolete. Interactions between acinar and islet tissues have been well established through numerous studies that reveal the existence of anatomical and functional relationships between these compartments of the gland. Less attention, however, has traditionally been paid to the relationships occurring between the endocrine pancreas and the ductal system. Associations between islet tissue and ducts are considered by most researchers as only a transient epiphenomenon of endocrine development. This article reviews the evidence that has emerged in the last 10 years demonstrating the existence of stable, close, and systematic relationships between these two pancreatic compartments. Functional and pathophysiological implications are considered, and the existence of an "acinar-duct-islet" axis is put forward. The pancreas appears at present to be an integrated organ composed of three functionally related components of well-orchestrated endocrine and exocrine physiological responses.mixedBERTELLI, Eugenio; BENDAYAN, MoiseBertelli, Eugenio; Bendayan, Mois