Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.     

Thermal behaviour of highly stereoregular syndiotactic polypropene from homogeneous catalysts

Thermal characterization was carried out on highly stereoregular and regioregular syndiotactic polypropene (sPP) obtained with isopropylidene(cyclopentadienyl)(9-fluorenyl)zirconium dichloride and methylaluminoxane. The influence of molecular weight and syndiotacticity degree on the thermodynamic melting point (T°_m) of sPP were separately investigated by examining samples with a fully syndiotactic pentads content (rrrr) ranging from ca. 81% to ca. 94% and with an weight-average molecular weight (M?_w) ranging from 9,6 · 10⁴ to 17,3 · 10⁴. Upon excluding any influence of the molecular weight, the correlation between the rrrr pentads content and the T°_m of the samples led to the extrapolation of the thermodynamic melting point for a fully syndiotactic polypropene.     

Upper extremity deep vein thrombosis after suspension of progesterone-only oral treatment.

The intake of steroid hormone contraceptives is a strong and independent risk factor for venous thromboembolism. Several studies have assessed an increased risk of venous thromboembolism in women using oral contraceptives who are carriers of the G20210A mutation in the prothrombin gene. Most trials evaluating the thrombotic risk of oral contraceptives are based on combined oral preparations, but only a few focus on progestogen-only oral preparations. Results from such studies are conflicting and globally assess the thrombotic risk, ranging from modest to slightly increased. Furthermore, little is known about the relationship between the C677T mutation in the methylenetetrahydrofolate reductase gene and the progestogen-based preparations. Herewith we report the case of a 49-year-old woman with a complex genetic thrombosis risk factor who had taken oral progesterone for 15 months without any complication, but then experienced severe left upper extremity deep vein thrombosis 2 months after the drug suspension.     

Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations

Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.     

Iodine toxicity secondary to continuous povidone-iodine mediastinal irrigation in dogs

Mediastinitis is a devastating complication following median sternotomy. Continuous povidone-iodine (PVP-I) irrigation has been advocated as therapy because of its broad antimicrobial spectrum and its apparent safety. However, several recent clinical reports have warned of suspected local and systemic iodine toxicity. The purpose of this study is to determine if significant amounts of iodine can be absorbed systemically via the mediastinum, and if so, what toxicity (local and/or systemic) may result. PVP-I (0.5%) was continuously irrigated into the pericardial sacs of three dogs via catheters for 48 hr. Serial serum and urine iodine levels were determined. The serum steady-state concentration (Css), the rate elimination constant (k), the urinary clearance (Cl), and the serum half-life (t 1/2) for iodine were assessed. Serum electrolytes, Bun, Cr, and arterial pH were measured to assess systemic iodine toxicity. Tissue samples of the heart, pericardium, liver, and kidney were examined histologically for evidence of local or end-organ iodine toxicity. This study demonstrated that the absorption of iodine during continuous mediastinal irrigation with PVP-I follows zero-order pharmacokinetics, just as if it were being given by continuous intravenous infusion. The baseline serum iodine concentration was 145.9 +/- 64.3 micrograms/dl, Css was 29,290 +/- 101.4 micrograms/dl, k was 0.0996 +/- 0.009/hr, Cl was 872.4 +/- 119.3 ml/hr, and t1/2 was 6.22 hr. Urinary excretion of iodine increased in proportion to the serum iodine. Measured serum chloride increased in a linear manner (r = 0.949), while serum Na, K, Bun, Cr, and pH were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cystic Medullary Thyroid Carcinoma: Report of a Case with Morphological and Clinical Correlations

Cystic lesions of the thyroid are common findings. Although many thyroid cysts are of benign, some cases of hemorrhagic degenerative changes occur in neoplastic nodules, mostly follicular neoplasms and papillary carcinomas. The occurrence of hemorrhagic changes in medullary carcinomas has never been documented with aspirative cytological and histological pictures to the best of our knowledge. A case of medullary thyroid carcinoma with a large central hemorrhagic cyst is described, and the literature regarding the pathogenesis of this regression and the occurrence of cystic neoplasms in the thyroid is reviewed.     

Simple Trends in the Methylene and α‐Substituent Regions of NMR Spectra of Vinyl Polymers

Summary: Chemical shift trends in the methylene and α substituent regions of ¹³C NMR spectra of vinyl polymers have been analyzed in terms of a three‐state rotational isomeric states (RIS) model and the γ‐gauche effect. In this framework, it has been demonstrated that the three sequencing rules observed for poly(propylene) can also be expected to work for many other vinyl polymers. The first two rules, justified in terms of the conformational perturbability of stereosequences, turn out to be respected by a considerable number of NMR spectra. On the other hand, the same spectral data are in substantial disagreement with the third rule. An explanation is proposed for this breakdown.

Sketches of the three conformations expected for rotation on the two prochiral bonds flanking the methine carbon of a vinyl polymer.