Squalenoyl-gemcitabine/edelfosine nanoassemblies: Anticancer activity in pediatric cancer cells and pharmacokinetic profile in mice.

Despite the great advances accomplished in the treatment of pediatric cancers, recurrences and metastases still exacerbate prognosis in some aggressive solid tumors such as neuroblastoma and osteosarcoma. In view of the poor efficacy and toxicity of current chemotherapeutic treatments, we propose a single multitherapeutic nanotechnology-based strategy by co-assembling in the same nanodevice two amphiphilic antitumor agents: squalenoyl-gemcitabine and edelfosine. Homogeneous batches of nanoassemblies were easily formulated by the nanoprecipitation method. Their anticancer activity was tested in pediatric cancer cell lines and pharmacokinetic studies were performed in mice. In vitro assays revealed a synergistic effect when gemcitabine was co-administered with edelfosine. Squalenoyl-gemcitabine/edelfosine nanoassemblies were found to be capable of intracellular translocation in patient-derived metastatic pediatric osteosarcoma cells and showed a better antitumor profile than squalenoyl-gemcitabine nanoassemblies alone. The intravenous administration of this combinatorial nanomedicine in mice exhibited a controlled release behavior of gemcitabine and diminished edelfosine plasma peak concentrations. These findings make it a suitable pre-clinical candidate for childhood cancer therapy.

Immunotoxicity of poly (lactic-co-glycolic acid) nanoparticles: influence of surface properties on dendritic cell activation.

Modified nanoparticles (NPs) can interact with the immune system by causing its activation to fight tumors or for vaccination. During this activation, dendritic cells (DCs) are effective in generating robust immune response. However, the effect of nanomaterials on dendritic cell (DC) maturation, and the associated adjuvant effect, should be assessed as a novel biocompatibility criteria for biomaterials since immune consequences may constitute potential complications in nanomedicine. Among emerging biomaterials, poly(lactic-co-glycolic acid) NPs (PLGA NPs) are widely explored for various applications in which the degree of desired adjuvant effect may vary. As contradictory results are reported regarding their effects on DCs, we aimed at clarifying this point with particular emphasis on the relative impact of particle surface properties. To that end, NP uptake and effects on the viability, phenotype, and secretory activity of DC primary cultures. Intracellular signaling pathways were explored and evaluated. Immature human and murine DCs were exposed to cationic, neutral, or anionic PLGA NPs. Particle uptake was assessed by both confocal microscopy and flow cytometry. Cell viability was then evaluated prior to the study of maturation by examination of both surface marker expression and cytokine release. Our results demonstrate that PLGA NPs are rapidly engulfed by DCs and do not exert cytotoxic effects. However, upon exposure to PLGA NPs, DCs showed phenotypes and cytokine secretion profiles consistent with maturation which resulted, at least in part, from the transient intracellular activation of mitogen-activated protein kinases (MAPKs). Interestingly, NP-specific stimulation patterns were observed since NP surface properties had a sensible influence on the various parameters measured.

Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case-control study.

Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.

Immediately loaded dental implants bioactivated with platelet-rich plasma (PRP) placed in maxillary and mandibular region.

BACKGROUND AND AIM: Dental implants have today deeply changed the dental field. In fact, after almost 50 years, the permanent placement of a titanium screw with an attached tooth have, step by step, changed the society's standard toward a permanently replacement of missed or severely damaged teeth. In fact, the host of benefits born from dental implants have affected both patients and dental professionals. The aim of the present study is to report the outcomes of an implant therapy protocol supporting fixed prostheses implanted soon after extractions and loaded with flapless guided surgery by a 3D software planning. MATERIALS AND METHODS: 37 patients, requiring rehabilitation of booth dental arches with a one-to-one technique, were enrolled in a follow-up study plan which established clinical and radiological examinations on the day after surgery, seven months and one year later. Platelet Rich Plasma (PRP), in combination with autogenous bone, organic bone material and organic bone substitutes, was used before implant-prosthetic rehabilitation with an its prompt loading just before the implant insertion phase. RESULTS: Definitive restorations were delivered at 6-12 months after surgical procedure. One year after loading there were no dropouts and no failure of the definitive prosthesis. Furthermore, the feedback from patients resulted positive. CONCLUSIONS: Patients resulted satisfied both aesthetically and functionally regarding these types of prosthetic reconstructions made at the time.

Chitosomes as drug delivery systems for C-phycocyanin: preparation and characterization.

The aim of this work was to investigate chitosomes, i.e. liposomes coated by a polyelectrolyte complex between chitosan (CH) and xantan gum (XG), as potential delivery system for oral administration of the protein C-phycocyanin. To this purpose several CH-XG-microcomplexes were prepared in aqueous lactic acid at different chitosan-xanthan gum percent ratios and rheological properties of the microcomplexes were studied to analyse the contribution of chitosan and xanthan gum in the reaction of microcomplexation. After establishing the best microcomplexes, chitosomes were prepared by coating C-phycocyanin loaded liposomes with the CH-XG hydrogels using spray-drying or freeze-drying. The chitosomes were characterized in terms of morphology, size distribution, zeta potential, swelling properties, drug release, and mucoadhesive properties. Rheological studies showed the influence of xanthan gum in the microcomplex properties. Moreover, obtained results demonstrated the effects of formulation and process variables on particle size, drug content, swelling, drug release, and especially on the mucoadhesiveness of C-PC chitosomes of CH-XG. In particular, chitosomes prepared by spray-drying technique using CH-XG in 0.5/8.0 (w/w) ratio showed a regular surface and a drug release characteristic for a Fickian diffusion of the active ingredient. The in vitro mucoadhesive study revealed that the spray-drying method is advantageous to prepare C-phycocyanin loaded chitosomes with excellent mucoadhesive properties for colonic drug delivery.

Radioimmunological detection of anti-transglutaminase autoantibodies in human saliva: a useful test to monitor coeliac disease follow-up.

BACKGROUND: Serum radioimmunoassay (RIA) tissue transglutaminase autoantibodies (tTG-Abs) proved to be a sensitive test also during coeliac disease (CD) follow-up. We demonstrated that RIA tTG-Abs could be detected in human saliva. AIM: To evaluate salivary RIA tTG-Abs in coeliac children on gluten-free diet (GFD). METHODS: Saliva and serum samples from 109 coeliac children were evaluated at diagnosis (group 1: 71 females, median age 9.4 years) and 58 of them on GFD: 36 after 3-6 months (group 2a), 34 at 9 months or more (group 2b). Two gender- and age-matched control groups: 89 gastroenterological patients (group 3) and 49 healthy subjects (group 4) participated in the study. Saliva and serum tTG-Abs were detected by RIA and compared with serum tTG-Abs ELISA and IgA anti-endomysium antibodies (EMA). RESULTS: Salivary RIA tTG-Abs were found in 94.5%, 66.7% and 50.0% of groups 1, 2a and 2b CD patients and in 98.2%, 72.2% and 50.0% of corresponding serum samples, respectively. tTG-Abs decreased with GFD progression and a correlation was found between saliva and serum titres (r = 0.75, P = 0.0001). During the CD follow-up, salivary and serum RIA sensitivities were comparable, and higher with respect to EMA and ELISA. CONCLUSIONS: This study demonstrates that it is possible to detect salivary tTG-Abs with high sensitivity not only at CD diagnosis, but also during GFD.

Early transabdominal chorionic villus sampling in couples at high genetic risk.

OBJECTIVE: The purpose of the study was to evaluate the feasibility and safety of transabdominal chorionic villus sampling before 9 weeks' gestation. STUDY DESIGN: Two hundred pregnancies at risk for beta-thalassemia (n = 198) or Duchenne muscular dystrophy (n = 2) underwent transabdominal CVS at 6 through 8 weeks. Sampling success and fetal loss are expressed in percentages. RESULTS: Sampling was successful in all cases (100%). Forty-eight fetuses were affected by beta-thalassemia and one by Duchenne muscular dystrophy. The percentage of fetal loss, expressed as a proportion of continuing pregnancies, was 4.0%. All women (n = 144) have been delivered, and no misdiagnoses have occurred. We observed one anencephalus and one mild limb defect consisting of absence of distal phalanges of index and little fingers of both hands and distal phalanges of both little toes. CONCLUSION: Transabdominal CVS before 9 weeks is a reliable and relatively safe method for prenatal diagnosis in patients at high risk for genetic diseases. However, further studies are necessary to assess the risk to the fetus.

[Measles and rubella in the city of Carbonia]. / Morbillo e rosolia nel comune di Carbonia.

The Italian "Consiglio Sanitario Nazionale", in the report about the years 1984 to 1986, emphasized the role of immunization programmes in order to reduce the scale of epidemics of measles and rubella. In this research work self-administered questionnaires have been used to study the incidence of measles and rubella in the infant population (1990 students) of the city of Carbonia (30000 inhabitants). Data analysis has been carried out by an exponential model. The force of infection "h" is the per capita rate at which susceptible individuals acquire infection. The force of infection represents the totality of a variety of factors that determine transmission of infection. For measles and rubella, the force of infection appears to increase linearly by age for people under 7-8 years old. In spite of this, as far as our study where the children are 3-10 years old is concerned, we can take it to be a constant. Under these conditions the proportion (y) of susceptibles at age x is given by y = exp (-(a + hx)). The equation may be modified to make calculations easier. We can write: ln y = z. The parameters "a" and "h" and the estimated values can be determined using linear regression. We can also calculate the 95% percent confidence intervals. The magnitude of both the coefficients of determination (R2 = 0.976 for measles; R2 = 0.932 for rubella) is suggestive for a good fitting. The force of infection is much higher for measles (h = 0.186 + 0.029) than for rubella (h = 0.035 + 0.009).

Contribucion de las tecnicas por imagenes para estudio y adecuacion del tratamiento en el epitelioma cuniculatem

Los hallazgos del diagnóstico por imágenes, en un caso de epitelioma cuniculatum com recaída son comentados favorablemente. Creemos que estos medios deben recordarse en las patologías de similar comportamiento biológico y en casos problemas con la precaución debida a toda nueva técnica. En nuestro caso, la ecografía y la xeroradiografía fueron los métodos que aportaron los datos más valiosos

Contribucion de las tecnicas por imagenes para estudio y adecuacion del tratamiento en el epitelioma cuniculatem

Los hallazgos del diagnóstico por imágenes, en un caso de epitelioma cuniculatum com recaída son comentados favorablemente. Creemos que estos medios deben recordarse en las patologías de similar comportamiento biológico y en casos problemas con la precaución debida a toda nueva técnica. En nuestro caso, la ecografía y la xeroradiografía fueron los métodos que aportaron los datos más valiosos (AU)

Evaluation of the Amniostat-FLM assay for assessment of fetal lung maturity.

Results of the "Amniostat-FLM" assay, a rapid semiquantitative test for phosphatidylglycerol, were compared with determinations of the lecithin/sphingomyelin (L/S) ratio, with phosphatidylglycerol measured by two-dimensional thin-layer chromatography, and with results of the "shake test" for 94 specimens of amniotic fluid. Correlation between results with the Amniostat and the other tests was excellent. All four tests are very accurate when predicting lung maturity. The predictive value of a negative test, i.e., that hyaline membrane disease would not occur, was between 92 and 100%. However, the accuracy of predicted lung immaturity is poor. For all four tests, predictions of lung immaturity were incorrect in more than 50% of the cases. Of the 49 infants born within 72 h of testing, none developed hyaline membrane disease when phosphatidylglycerol was detectable by either method or when the shake test indicated fetal lung maturity, but three infants with L/S ratio greater than 2/1 did develop the disease. The Amniostat provides a rapid screening method for detecting phosphatidylglycerol in amniotic fluid, which could well replace the thin-layer chromatographic method for measuring phosphatidylglycerol in the panel of diagnostic tests for fetal lung maturity.

Epiteliomatosis basocelular? / Basal cell epithelioma

Se describe una pacientes con 283 epiteliomas basocelulares sin afeccion precancerosa definida. En vista de otros casos conocidos se propone revisar el tema y se invita a la publicacion de casos analogos sugiriendo mantener epiteliomatosis basocelular como un termino generico de hipotesis de trabajo, ya que no puede descartarse prima facie una entidad precancerosa aun no definida

Epiteliomatosis basocelular? / Basal cell epithelioma

Se describe una pacientes con 283 epiteliomas basocelulares sin afeccion precancerosa definida. En vista de otros casos conocidos se propone revisar el tema y se invita a la publicacion de casos analogos sugiriendo mantener epiteliomatosis basocelular como un termino generico de hipotesis de trabajo, ya que no puede descartarse prima facie una entidad precancerosa aun no definida

Rosacea. Tratamiento eficaz con la asociacion acido glutamico-pepsina. / Rosacea. Efficient treatment with the association glutamic and pepsin

En este estudio de 119 casos de rosacea hecho en 3 anos con 300 mg de acido glutamico y 75 UI de pepsina en 3 tomas diarias encontramos excelentes resultados, mejoria de los sintomas dermatologicos, psiquicos, gastricos y oculares.Normalizacion del aspecto general y disminucion del tamano de las glandulas sebaceas en el estudio postratamiento

Rosacea. Tratamiento eficaz con la asociacion acido glutamico-pepsina. / Rosacea. Efficient treatment with the association glutamic and pepsin

En este estudio de 119 casos de rosacea hecho en 3 anos con 300 mg de acido glutamico y 75 UI de pepsina en 3 tomas diarias encontramos excelentes resultados, mejoria de los sintomas dermatologicos, psiquicos, gastricos y oculares.Normalizacion del aspecto general y disminucion del tamano de las glandulas sebaceas en el estudio postratamiento

Variantes clinicas del carcinoma verrugoso: epitelioma cuniculatum, piodermitis vegetante. / Clinical variants of verrucous carcinoma: epithelioma caniculatum, pyodermitis

Presentamos casos de lo que consideramos variantes del C.V.: A) Piodermitis vegetante "pseudoepiteliomatosa" (Juan DAzua) un caso en tratamiento, con buena evolucion. B) Epitelioma cuniculatum (Aird), tres casos con curacion, en los dos que siguieron el tratamiento, y mejoria en el paciente de dificil seguimiento. La terapeutica instituida fue, salvo un caso, MTX intralesional con efecto curativo en los dos pacientes que cumplieron las indicaciones. Destacamos la variacion clinica de ep. cuniculatum a C.V. al eliminar la presion corporal con ortesis de confeccion casera tipo taco de marcha. Analizamos los criterios clinicos, histologicos, terapeuticos y evolutivos que no nos permiten separar, al menos por ahora, el ep. cuniculatum del C.V

Variantes clinicas del carcinoma verrugoso: epitelioma cuniculatum, piodermitis vegetante. / Clinical variants of verrucous carcinoma: epithelioma caniculatum, pyodermitis

Presentamos casos de lo que consideramos variantes del C.V.: A) Piodermitis vegetante "pseudoepiteliomatosa" (Juan D'Azua) un caso en tratamiento, con buena evolucion. B) Epitelioma cuniculatum (Aird), tres casos con curacion, en los dos que siguieron el tratamiento, y mejoria en el paciente de dificil seguimiento. La terapeutica instituida fue, salvo un caso, MTX intralesional con efecto curativo en los dos pacientes que cumplieron las indicaciones. Destacamos la variacion clinica de ep. cuniculatum a C.V. al eliminar la presion corporal con ortesis de confeccion casera tipo taco de marcha. Analizamos los criterios clinicos, histologicos, terapeuticos y evolutivos que no nos permiten separar, al menos por ahora, el ep. cuniculatum del C.V