Nanocarriers to Enhance the Accumulation of Vitamin K1 into the Skin

Purpose

Vitamin K1 (VK1) is a molecule abundant in some species of leaf vegetables with beneficial effects in humans following administration on the skin. This work investigates the possibility to use formulations based on lipid vesicles, namely liposomes, transfersomes and ethosomes, suitable to be administered on the skin by nebulization and alternative to fat semisolid preparations present on the market.

Methods

Lipid vesicles encapsulating VK1 were prepared and characterized. Ex-vivo experiments on Franz cells were carried out to study the VK1 accumulation/permeation in/through the skin. Vesicles interaction with the skin was investigated by confocal laser scanning microscopy (CLSM) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy.

Results

All developed carriers were stable following long-term storage and were not altered following nebulization. In ex-vivo experiments, vesicles with the highest deformability index, namely transfersomes and ethosomes, led to an enhanced VK1 accumulation/permeation into/through the skin. Interestingly, the nebulization of the vesicles led to a further increase of VK1 accumulation into the skin.

Conclusions

In conclusion, to achieve a local effect of VK1 on the skin, the topical nebulization of VK1-containing transfersomes could offer a good compromise between a high VK1 penetration into the skin and a limited permeation through it.

     

Clinical parameters predicting tonsillar malignancy

European Archives of Oto-Rhino-Laryngology - Tonsillectomy is indicated in unilateral tonsillar enlargement (UTE) to rule out malignancy, which eventually is found in about 1.4% of the patients....     

Caregiver quality of life in multiple sclerosis: a multicentre Italian study

The purpose of this study was to evaluate the quality of life (QoL) of multiple sclerosis (MS) caregivers, and to determine relationships that may exist between caregiver and patient QoL. Patients with definite MS (n=445) and their caregivers (n=445) were required to complete the generic, 36-item short-form (SF-36) Health Survey. Median SF-36 dimension scores ranged from 55 to 100 for caregivers and from 46 to 78 for patients. Although the QoL of MS carers was not as severely affected as that of patients, caregiving was associated with lower mental health, vitality and general health scores, compared to healthy subjects. Multivariate analyses revealed significant differences between the predictors of patient QoL and caregiver QoL. The main predictors of patient QoL were Expanded Disability Status Scale (EDSS) score, MS course, fatigue and depression. Female gender and advanced age were the main predictors of lower QoL in caregivers. In addition, patient BDI score was found to be a significant predictor of almost all caregiver SF-36 dimension scores, while EDSS score, disease duration and course, and patient therapeutic characteristics were found to be predictors of some caregiver SF-36 dimension scores. Therefore, caregiver QoL was significantly influenced by patient characteristics, and supportive strategies for MS caregivers are warranted.     

Re-treatment with interferon-beta of patients with chronic hepatitis C virus infection

OBJECTIVE: To evaluate the efficacy of interferon-beta (IFN-beta) in the re-treatment of patients with chronic hepatitis C who did not respond to IFN-alpha monotherapy. PATIENTS AND METHODS: Thirty patients (24 men and six women; mean age, 41 +/- 13 (SD) years; range, 23-62 years), with chronic hepatitis C that was non-responsive to a standard course of IFN-alpha therapy, were re-treated with recombinant human IFN-beta-1a. All patients received IFN-beta, 12 MIU subcutaneously, three times weekly for 3 months, after which time patients' responses were evaluated. Responders (normal alanine aminotransferase, and negative for serum hepatitis C virus RNA) continued to receive IFN-beta, 12 MIU, for a further 3 months. Non-responders had their dose increased to 18 MIU for the remaining 3 months of treatment. After 6 months of treatment, therapy was stopped and patients were followed-up for a further 6 months. RESULTS: Overall, six (20%) of the 30 patients exhibited a response at the end of treatment. One patient (3.3%) maintained a sustained virological response at the end of post-treatment follow-up. CONCLUSIONS: Treatment with recombinant IFN-beta, at doses of up to 18 MIU for 6 months, is safe and well tolerated. However, the results of the trial do not support the use of IFN-beta monotherapy in patients with chronic hepatitis C that is resistant to IFN-alpha.     

Fluid-Structure Finite-Element Modelling and Clinical Measurement of the Wideband Acoustic Input Admittance of the Newborn Ear Canal and Middle Ear

The anatomical differences between the newborn ear and the adult one result in different input admittance responses in newborns than those in adults. Taking into account fluid-structure interactions, we have developed a finite-element model to investigate the wideband admittance responses of the ear canal and middle ear in newborns for frequencies up to 10 kHz. We have also performed admittance measurements on a group of 23 infants with ages between 14 and 28 days, for frequencies from 250 to 8000 Hz with 1/12-octave resolution. Sensitivity analyses of the model were performed to investigate the contributions of the ear canal and middle ear to the overall admittance responses, as well as the effects of the material parameters, measurement location and geometrical variability. The model was validated by comparison with our new data and with data from the literature. The model provides a quantitative understanding of the canal and middle-ear resonances around 500 and 1800 Hz, respectively, and also predicts the effects of the first resonance mode of the middle-ear cavity (around 6 kHz) as well as the first and second standing-wave modes in the ear canal (around 7.2 and 9.6 kHz, respectively), which may explain features seen in our high-frequency-resolution clinical measurements.     

Finite-Element Modelling of the Acoustic Input Admittance of the Newborn Ear Canal and Middle Ear

Admittance measurement is a promising tool for evaluating the status of the middle ear in newborns. However, the newborn ear is anatomically very different from the adult one, and the acoustic input admittance is different than in adults. To aid in understanding the differences, a finite-element model of the newborn ear canal and middle ear was developed and its behaviour was studied for frequencies up to 2000 Hz. Material properties were taken from previous measurements and estimates. The simulation results were within the range of clinical admittance measurements made in newborns. Sensitivity analyses of the material properties show that in the canal model, the maximum admittance and the frequency at which that maximum admittance occurs are affected mainly by the stiffness parameter; in the middle-ear model, the damping is as important as the stiffness in influencing the maximum admittance magnitude but its effect on the corresponding frequency is negligible. Scaling up the geometries increases the admittance magnitude and shifts the resonances to lower frequencies. The results suggest that admittance measurements can provide more information about the condition of the middle ear when made at multiple frequencies around its resonance.     

Reduced bone mass and normal calcium metabolism in systemic sclerosis with and without calcinosis

Summary Forty-three female patients with systemic sclerosis divided into subgroups based on the extent of skin involvement and the presence of calcinosis, and 50 sex and age-matched healthy controls were investigated for bone mineral density (BMD) on the basis of radial (dual photon absorptiometry, Osteograph, NIM), lumbar, and total body measurements (dual energy X-ray absorptiometry, Lunar DPX, Lunar Corp.), and for parameters of calcium metabolism. The patients showed a lower BMD (mean±SD; mg/cm²) than the controls at the radial (313±69 vs 347±73; p<0.005), lumbar (974±143 vs 1081±154; p<0.005), and total body (997±82 vs 1075±109; p<0.05) determinations. The patients with the diffuse form of skin involvement had lower values than those with the limited form. There was a negative correlation between BMD and the duration of the disease. The presence of calcinosis was not found to have any effect on BMD. Calcium metabolism was found to be normal in each subgroup.It may be concluded that generalized osteoporosis is a feature of systemic sclerosis, with and without calcinosis. The extent and duration of the disease may play a role in determining bone loss.