Repurposing itraconazole to the benefit of skin cancer treatment: A combined azole-DDAB nanoencapsulation strategy.

In this work, we aimed at developing an improved topical SLN formulation combining itraconazole delivery with a coating layer of didodecyldimethylammonium bromide, thus repurposing the drug effectiveness by synergistic skin anticancer effectiveness. In order to obtain a stable SLN formulation with small homogeneously dispersed particles, a deep formulative study was developed screening three different solid lipids (Suppocire NB, Cetyl Palmitate and Dynasan 114) for the SLN preparation by the phase inversion temperature. A bluishcolored shade formulation, with homogeneous small particles size (<50 nm) was obtained only using Suppocire NB. The cytotoxicity of all SLN was tested after 24 h exposure against three adherent skin cell lines (A431, HaCaT and SK-MEL-5). Results demonstrate that both unloaded and drugloaded SLN did not significantly affect the cell viability of the non-tumoral HaCaT cell line, thus confirming the safe potential topical application of these formulations. A dose-dependent decrease in cell viability was observed for the tumoral cell lines, A431 and SK-MEL-5, with a significant reduction of the A431 cancer cell line viability. The drug molecule addition to the uncoated nanoparticles was able to increase of almost 20% the reduction of the viability of the cancer cells treated. Ours results demonstrate the potentiality of repurposing itraconazole activity by using the combined nanoencapsulation strategy with the positively charged coating layer on SLN, which can be further investigated as a promising stable and safe approach to significantly reduce the viability of skin cancer cells.

Innovative hybrid vs polymeric nanocapsules: The influence of the cationic lipid coating on the "4S".

Polymeric and hybrid aqueous-core nanocapsules were prepared using a low energy organic-solvent free procedure as innovative nanodevices for the ophthalmic delivery of melatonin. In order to evaluate how different cationic lipids could affect the main properties of the nanodevices, we focused our attention on mean particles size, surface charge, shape and stability (the "4S"). The results of our study confirmed the hypothesis that the coating material differently affects the overall nanoparticles properties, above all in terms of morphology: in particular, the cationic lipid dimethyldioctadecylammonium bromide allows the formation of very stable well-defined nanocapsules with non-spherical shape with sustained and prolonged drug release, thus representing a great advantage in ophthalmic application.

Immediate transmucosal implant placement in fresh maxillary and mandibular molar extraction sockets: description of technique and preliminary results.

AIM: The study was designed to evaluate the clinical treatment outcome of placing transmucosal implants into extraction. The purpose of the present clinical study was to test whether peri-implant bone defects can successfully be filled by applying both the bone and the bioresorbable materials for the guided tissue regeneration. METHODS: Twelve patients who required extraction of a single molar were treated with immediate placement of an ITI implant (Dental Implant System). Guided bone regeneration (GBR) technique was always applied simultaneously using deproteinized bovine bone mineral. Implants and bone were covered with a resorbable collagen membrane. Clinical measurements were taken at 6 sites around each implant. Radiological and clinical parameters were measured at the time of implant placement and at follow-up after 1, 3, 6, 12 and 24 months. Prosthetic rehabilitation was performed 3 months after surgery using a porcelain fused to metal crown. RESULTS: Soft tissue healing, at all sites, was free of complications, independently on the width of bone defect. Radiographs showed strength contact between peri-implant bone and the fixture without any defect between bone and implant. Clinical examination showed absolute implant stability complying with Albrekts-son's requirements. CONCLUSIONS: The use of GBR with resorbable membrane to cover Bio-oss, in association with immediate implant insertion at posterior sites when there is a wide bone defect, also allows early defect filling and good stability, already in the first month, with the possibility of prosthetic loading after only 3 months.

An electrochemical impedance investigation of the behaviour of anodically oxidised titanium in human plasma and cognate fluids, relevant to dental applications.

In dental applications, the contact between the metal implant and the receiving living tissue is made through the oxide layer on the implant surface, which allows the osseointegration process. In dentistry, the passive film formed on titanium seems to be more stable and protective than that formed on the Ti alloys, customarily used in other medical applications. Corrosion of titanium alloys in the mouth can result from the presence of a number of corrosive species, such as the hydrogen ion (H(+)), sulfide compounds (S(2-)), dissolved oxygen (O(2)) and Cl(-) and can result in the release of Ti(4+) ions that, in turn, brings about the reduction of alkaline phosphatase activity of osteoblastic cells. The present study reports a time-dependent electrochemical corrosion study of titanium in contact with the following biologically relevant solutions: (i) SBF (simulating the inorganic part of human plasma), (ii) SBF with added ovalbumin (a protein simulating the post-implant environment) and (iii) human plasma. To the best of the authors' knowledge, this is the first report on the corrosion of Ti in human plasma. The electrochemical measurements are based on electrochemical impedance spectrometry. Impedance spectra were interpreted on the basis of the equivalent-circuit approach and estimates of the time-variation of oxide film thickness and resistance were computed. Surface Raman spectroscopy was used to characterise the structure of as-anodised and corroded TiO(2) films: the effects of phosphate and organic incorporation were highlighted. EIS and surface Raman measurements have demonstrated that the corrosion resistance of the oxide films formed on Ti is strongly affected by the presence of biomolecules in the chloride- and phosphate-based aqueous solution. In particular, ovalbumin increases corrosion performance and human plasma is found to be remarkably more aggressive in comparison to SBF. These results suggest some caution in extrapolating corrosion results obtained in simulated biological fluids to the actual behaviour in vivo.

[Interaction between prescribers, dispensers, and patients: shared information as a possible therapeutic benefit]. / A interação entre prescritores, dispensadores e pacientes: informação compartilhada como possível benefício terapêutico.

The article presents a critical view of the interaction between prescribers, dispensers, and patients, considering information one of the key issues in enhancing the qualitative aspects involved in this complex relationship. It describes the acquisition of information by health professionals, possible sources of this information, and the process involved in transforming it into knowledge. Briefly discussed are the physician's and pharmacist's roles, the patient's expectations as recipient, and consequences of pertinent health interventions.

Bone metabolism changes after transdermal estradiol dose reduction during estrogen replacement therapy: a 1-year prospective study.

Twenty-four surgically menopausal women were randomly allocated to one of two transdermally-administered estrogen replacement therapies (ERT): Group A was administered Estradiol (E2) TTS 0.05 mg/day for 6 months and 0.025 mg/day for the following six months and group B, E2 TTS 0.10 mg/day for the first 6 months and 0.05 mg/day for the following 6 months. For both groups, the treatment regimen was based upon the twice-weekly application of transdermal patches to the lower abdomen for three weeks a month. Serum E2, alkaline phosphatase (AP), osteocalcin (BGP) and urinary hydroxyproline (OHP) excretion levels were measured before the operation, at the beginning of ERT and after 6 and 12 months of treatment. Bone mineral density (BMD) in the distal regions of the forearms was measured by single photon absorptiometry at the start of the study and after 6 and 12 months. In Group A, both mean cortical and trabecular BMD had increased by, respectively, 1.53% and 2.17% after 6 months of therapy; after the second 6 months a significant decrease was observed in both parameters (2.40% and 3.62%, respectively). In Group B, mean cortical and trabecular BMD increased by 1.50% and 2.10%, respectively (significant increase in trabecular bone) after the first 6 months of treatment; after the following 6 months, these values persisted (+0.15 and -0.03%, respectively). Mean AP, OHP and BGP serum levels rose after the operation. In Group A, AP and OHP showed a significant decrease after the first 6 months (-34.90% and -30.90%), followed by an increase at the last evaluation of 22.50% and 35.50%, that reached statistical significance only for OHP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Consumption of psychotropic drugs in an Administrative Region of the city of Rio de Janeiro: Ilha do Governador]. / Consumo de psicofármacos em uma região administrativa do Rio de Janeiro: a Ilha do Governador.

In 1988, a cross-sectional survey was conducted to estimate the prevalence of alcoholism and alcohol consumption in the 20th Administrative Region of the city of Rio de Janeiro. The interview protocol included questions about consumption of psychotropics, coffee, and cigarettes. This paper presents data from psychotropic consumption in the month. The sample of the population older than 13 years old included 1,459 subjects. Overall consumption of psychotropic drugs was 5.2%. Rate of psychotropic use was higher for females (6.7%) than for males (3.1%). Users were predominantly women, elderly, (the highest rate was for those between 60-69 years), divorced or widows, and with lower family income. The association of each socio-demographic variable was evaluated by the odds ratio adjusted by logistic regression. Anxiolytics (benzodiazepines) predominated (85.23%) among the reported psychotropics, followed by antiepileptics (5.68%) and hypnotics and sedatives (4.54%). Physicians not specializing in neurology or psychiatry lead prescriptions (65.8%). 80.26% of the drugs were obtained in pharmacies, while 13.16% were obtained in governmental institutions, most of them by controlled prescriptions. The results are discussed and new lines of research are suggested.

Gene transfer of immunoglobulin light chain restores heavy chain secretion.

Several lines of evidence suggest that immunoglobulin (Ig) light (L) chain plays a role in the secretion of heavy (H) chain. For example, myeloma variant lines, which synthesize the Ig H chain but not the L chain, fail to secrete H chain protein. Here we have tested directly the role of chain assembly in the control of Ig secretion by the transfer of functional L chain genes into two such L chain-defective myeloma mutants. A lambda 2 or kappa L chain gene was introduced into variant lines of the mouse myelomas MOPC 315 (IgA, lambda 2) or PC7 (IgM, kappa), respectively. Although the two mutant lines are unable to secrete the H chain they produce, rescue of secretion of complete Ig protein molecules (IgA or IgM) was observed after transfection. These results imply that the secretory apparatus of these cells is intact and that the failure to secrete free H chain reflects a structural feature intrinsic to that protein. The implications of these results with respect to control of secretion of multi-subunit proteins are discussed.

Awareness of cognitive defences and stress management.

There is considerable disagreement regarding whether defences operate unconsciously, represent deliberate styles of coping with problems, or fall somewhere between. The present study considered the role of awareness in mediating the relation between defence and stress by establishing whether the conscious or unconscious nature of a given defence was associated with a distinct level of stress. The results for projection and rationalization confirmed the classical Freudian version of defence as an unconscious mechanism that reduces the stress of painful thoughts. Unconscious projectors and rationalizers reported singularly low levels of stress over the previous year. Repression without awareness was associated with a distinctly high level of stress, whereas denial with awareness was related to lower stress. While these results provide some support for the view that defences must be unconscious to work effectively, they also suggest the diversity among defences in the role played by awareness in coping with stress.

Specific regulation of c-myc oncogene expression in a murine B-cell lymphoma.

The c-myc oncogene has been implicated in a wide spectrum of B-cell neoplasias. In normal cells, the level of expression of the c-myc gene correlates with growth status. In the present study, we examined the effect of receptor-mediated inhibition of growth on c-myc expression in a B-cell lymphoma. The murine lymphoma line WEHI 231 has been characterized as an early B cell; it bears surface-bound IgM and has unrearranged c-myc genes. Following treatment of a WEHI 231 culture with anti-mouse Ig antiserum, the cells undergo one round of division and further proliferation is inhibited. We observed that this treatment specifically affected cytoplasmic levels of c-myc mRNA. An initial early increase is followed by a precipitous drop such that by 4 hr (after exposure) the amount of c-myc mRNA is below control values by a factor of approximately equal to 10. The drop in c-myc precedes cessation of DNA synthesis. During the 2- to 4-hr period, c-myc mRNA had a maximal half-life of between 20 and 30 min. In contrast, even 24 hr after anti-Ig exposure, the amounts of most major mRNAs, including mu heavy chain and actin, were not significantly altered. These results indicate that expression of an unrearranged c-myc gene can be selectively responsive to receptor-mediated regulatory events.

Overproduction of immunoglobulin mRNA by a murine myeloma MOPC 315 variant cell line.

The mouse myeloma MOPC 315 cell line synthesizes and secretes IgA (lambda 2) immunoglobulin. A spontaneously arising variant of the MOPC 315 line, which had been isolated as apparently oversecreting IgA protein, has been characterized. The variant line has been shown to synthesize and secrete increased levels of heavy chain, light chain, and J chain polypeptide compared to the parental wild-type cells from which it was isolated. The steady-state levels of cytoplasmic mRNA for these polypeptides are increased commensurately in the over-producing line. For the heavy chain, enhanced transcription, and possibly increased gene dosage, appear to be involved. The increased levels of the three individual immunoglobulin polypeptide chains suggest that the variant line displays a coordinate regulation of expression of immunoglobulin genes.

The value of urodynamic testing in stress urinary incontinence.

Preoperative urodynamic testing for the identification of specific types of urinary incontinence was found useful to select an appropriate operative procedure. Failure of the operation to relieve stress incontinence was unusual in 346 patients followed for a minimum of 2 years. Of the total group of patients with stress incontinence 27 per cent also had detrusor instability identified urodynamically preoperatively. However, identification of the syndrome is of limited prognostic significance since the majority of these patients had no difficulty with the syndrome postoperatively and some other patients appeared to have the syndrome only postoperatively.

Stress Urinary Incontinence.

Stress urinary incontinence (SUI) was studied in 125 women who were subjected to simultaneous urodynamic and radiologic evaluation. This included cystometry, urethral pressure profiles, measurement of effective urethral length, estimation of urethral mobility, and alterations in the urethrovesical angles during stress. The most common abnormality was a hypermobility of the proximal urethra with loss of its intraabdominal position during stress, associated with changes in the urethrovesical angle. Fixation of the posterior urethra, loss of effective urethral length, low resting urethral pressure, and true neurovesical dysfunction were also found in some of the patients. Uninhibited bladder contractions were found in 22% of cases, but in most instances they were the result of SUI and ceased after surgical repair.