Preparation,characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery

The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.     

Hydradenitis suppurativa and inflammatory bowel disease: An unusual,but existing association

Inflammatory bowel disease (IBD) could be associated with several extra-intestinal manifestations (EIMs) involving musculoskeletal, hepatopancreatobiliary, ocular, renal, and pulmonary systems, as well as the skin. In the last years, hidradenitis suppurativa (HS) is acquiring an increasing interest. IBD, especially Crohn’s disease (CD), is among the most reported associated diseases in HS patients. The aim of this paper is to give a brief overview of data showing a possible epidemiologic and pathogenetic association between IBD and HS. We performed a pooled-data analysis of four studies and pooled prevalence of HS in IBD patients was 12.8%, with a 95%CI of 11.7%-13.9%. HS was present in 17.3% of subjects with CD (95%CI: 15.5%-19.1%) and in 8.5% of UC patients (95%CI: 7.0%-9.9%). Some items, especially altered immune imbalance, are generally involved in IBD pathogenesis as well as invoked by HS. Smoking is one of the most relevant risk factors for both disorders, representing a predictor of their severity, despite, actually, there being a lack of studies analyzing a possible shared pathway. A role for inheritance in HS and CD pathogenesis has been supposed. Despite a genetic susceptibility having been demonstrated for both diseases, further studies are needed to investigate a genetic mutual route. Although the pathogenesis of IBD and HS is generally linked to alterations of the immune response, recent findings suggest a role for intestinal and skin microbiota, respectively. In detail, the frequent finding of Staphylococcus aureus and coagulase-negative staphylococci on HS cutaneous lesions suggests a bacterial involvement in disease pathogenesis. Moreover, microflora varies in the different cutaneous regions of the body and, consequently, two different profiles of HS patients have been identified on these bases. On the other hand, it is well-known that intestinal microbiota may be considered as “the explosive mixture” at the origin of IBD despite the exact relationship having not been completely clarified yet. A better comprehension of the role that some bacterial species play in the IBD pathogenesis may be essential to develop appropriate management strategies in the near future. A final point is represented by some similarities in the therapeutic management of HS and IBD, since they may be controlled by immunomodulatory drugs. In conclusion, an unregulated inflammation may cause the lesions typical of both HS and IBD, particularly when they coexist. However, this is still a largely unexplored field.     

Unresectable primary tumor of head and neck: does neck dissection combined with chemoradiotherapy improve survival?

A study regarding patients with primary and previously untreated advanced histologically proven squamous cell carcinoma of the head and neck was performed to compare two treatment modalities: neck dissection followed by chemoradiotherapy (Group I) versus chemoradiotherapy alone (Group II). Fifty-four patients were randomly chosen to receive Group I or II treatment. Our results demonstrate that Group I treatment has a higher and statistically significant disease-specific survival rate. We suggest that an association of neck dissection plus chemoradiotherapy can be useful in the event of unresectable advanced carcinomas.     

Oral lichen planus: a preliminary clinical study on treatment with tazarotene

OBJECTIVE: The rationale for using tazarotene in oral lichen planus (OLP) is its regulatory action on the growth and differentiation of keratinocytes and on inflammation. This randomized, placebo-controlled study addresses evaluation of the effects of topic tazarotene in the treatment of OLP. DESIGN: The degree of lesions before and after treatment scored by a 6-score scale in six cases treated with tazarotene was statistically compared with those of six controls treated with placebo. SUBJECTS: Twelve patients with hyperkeratosic OLP were randomly allocated to treatment with tazarotene gel 0.1% b.i.d. or with placebo for eight consecutive weeks. METHODS: The statistical comparison was executed by means of Wilcoxon analysis for paired data. RESULTS: Patients treated with tazarotene presented a significant reduction of their lesions as compared with the control group. Among transitory side-effects, burning sensation and taste abnormalities were observed. CONCLUSION: Topical tazarotene may be a valuable therapeutic tool in the treatment of hyperkeratotic OLP.     

Blood group A immunodeterminants on human red cells differ in biologic activity and sensitivity to alpha-N-acetylgalactosaminidase

BACKGROUND: Epitopes of blood group A antigen can be enzymatically cleaved from red cells (RBCs), but the extent of cleavage required for normal survival in allogeneic blood transfusion recipients is unknown. Therefore, the cleavage rates were studied for A antigen epitope binding of 1) complement-activating anti-A, 2) Dolichos biflorus anti- A, lectin, and 3) hemagglutinating anti-A during incubation with a purified alpha-N-acetylgalactosaminidase, E.C. 3.2.1.49 (alpha- GalNAc'ase). STUDY DESIGN AND METHODS: Suspensions of group A RBCs were incubated with alpha-GalNAc'ase. Cells were removed at intervals, washed, and tested for loss of binding by monoclonal, polyclonal, and complement-activating anti-A, D. biflorus anti-A1 lectin, and Ulex europaeus anti-H lectin. RESULTS: A epitopes binding D. biflorus lectin were highly susceptible to alpha-GalNAc'ase; simultaneously with their loss, binding with U. europaeus lectin emerged. Loss of complement- mediated hemolysis was slower. A epitopes binding hemagglutinating anti- A were most resistant. Cleavage of A epitopes from membrane glycosphingolipids with short oligosaccharide chains was similarly resistant. Rates of cleavage from A1 and A2 RBCs were similar. CONCLUSION: RBC epitopes of blood group A differ in susceptibility to cleavage and biologic reactivity, which suggests that subsets mediating important biologic functions exist on functionally and topographically distinct membrane glycoconjugates.     

Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.     

Open trial of cefepime (BMY 28142) for infections in hospitalized patients.

The safety and efficacy of cefepime, a new broad-spectrum, semisynthetic parenteral cephem antibiotic, were evaluated in an open trial at a single hospital. Seventy patients were treated with cefepime: 44 had lower respiratory tract infections, 4 had urinary tract infections, and 22 had skin or soft tissue infections. Of 65 clinically evaluable patients, 64 (98%) had satisfactory responses. No mortality or superinfections occurred. Of 57 respiratory and urinary tract pathogens, 54 (95%) were eradicated and 3 (5%) persisted after therapy. Five bacteremias (two with Streptococcus pneumoniae and one each with Staphylococcus aureus, Proteus mirabilis, and a coagulase-negative staphylococcus) were eradicated. MICs ranged from 1 to 8 micrograms/ml for 13 S. aureus and 9 Pseudomonas aeruginosa isolates and were less than or equal to 0.125 micrograms/ml for 10 streptococcal isolates. Adverse effects occurred in two patients: transient diarrhea and Clostridium difficile toxin in the stool in one patient and loose bowel movements and increased transaminases in the other patient. Cefepime appeared to be well tolerated in humans and was effective against a wide range of isolates, including S. aureus and P. aeruginosa.     

Contrast-Enhanced Spectral Mammography and tumor size assessment: a valuable tool for appropriate surgical management of breast lesions

Purpose

To compare the accuracy of Contrast-Enhanced Spectral Mammography (CESM), MG, US, and breast MRI in estimating the size of breast lesions requiring surgery. The postoperative histology size of the lesion was used as the gold standard.

Material and methods

Two hundred thirty-three non-benign lesions in 189 patients were included in the analyses. All the selected patients underwent CESM and at least one other conventional diagnostic exam (US, MG, or MRI). Subsequently, all the patients underwent surgery preceded by cytological/histological examination. The largest diameter of the lesion at imaging was measured by a radiologist with more than 10 years’ experience and then compared with the size of the lesion in the histological sample at the surgery (gold standard).

Results

Among the 233 breast lesions, 196 were evaluated with US, 206 with MG and 160 with MRI. We found no statistically significant differences between size measurements using CESM and MRI compared with the measurements at the surgery (p value 0.63 and 0.51), whereas a significant difference was found for MG and US (p?<?0.001).

Conclusion

CESM is a reliable method for estimating the size of breast lesions: its performance seems superior to US and MG and comparable to MRI.

     

Psodisk,a new visual method for assessing the burden of psoriasis on patients

Background The last decades have witnessed an increasing interest for the psychosocial aspects of chronic skin diseases, such as psoriasis. Nonetheless, systematic assessments of the impact of psoriasis on patients’ lives are rarely done in daily clinical practice. The existing instruments are mostly meant to be completed by patients alone, and rarely comprise a graphical representation of the results. Objective  To develop a questionnaire allowing both a quick assessment of the impact of psoriasis on patients and, at the same time, an intuitive graphic visualization of the outcome of the test. Methods A preliminary version of an Italian questionnaire aimed to assess the global impact of psoriasis on patients, meant to be filled in together by the patient and the dermatologist and to produce visual, intuitive results, was developed through focus groups. The instrument was then the object of a Delphi survey addressed to a panel of experts, to assess both the need of possible improvements of the questionnaire (in terms of the formulations of the questions and of the domains to be explored) and the usefulness of the questionnaire. Results A 10‐item questionnaire in Italian, taking into account different aspects of the burden of psoriasis on the patient, was developed. The answers are given on a 10‐point visual analogue scale and graphically represented on a disc as a polygon. Conclusions A formal validation of the questionnaire and a study to assess potential clinical and psychological benefits of a systematic implementation of the instrument in daily practice are planned.