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Biomedical subjects

Paolo Colombo

Publications and source records attributed to Paolo Colombo.

At least 19 recordsLinked to original sources
PubMed2006

Single-layer transdermal film containing lidocaine: modulation of drug release.

We have recently described an innovative drug delivery system, a water-based and vapor permeable film intended for dermal and/or transdermal delivery. The aim of this work was to modulate the delivery of the model drug lidocaine hydrochloride from the transdermal film across rabbit ear skin. The effect of drug loading, of film-forming polymer type and content, of adhesive and plasticizer on lidocaine transport across the skin was evaluated. Additional objective was to evaluate the effect of occlusion on the kinetics of lidocaine transport, by applying an occlusive backing on the surface of the transdermal film. From the data obtained it can be concluded that the transdermal film acts as a matrix controlling drug delivery. The film-forming polymer molecular weight had a negligible effect on drug penetration, while its content was more effective. The choice of the adhesive seems to be the most important variable governing drug transport. In particular, the presence of lauric acid combined with a basic drug, such as lidocaine, can produce a relevant improvement in permeation, because of the formation of an ion pair. Concerning the kinetics, drug depletion is responsible for the declining permeation rates observed in the late times of permeation.

Administration, Cutaneous↗
PubMed2006

In vivo and in vitro investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos.

Artemisinin derivatives are clinically effective and safe antimalarials, but are not recommended during the first trimester of pregnancy because of the resorptions and abnormalities seen in animal reproduction studies. Understanding how, when and what toxicity occurs is crucial to any assessment of clinical relevance. Previously, DHA has been shown in the rat whole embryo culture (WEC) to primarily affect primitive red blood cells (RBCs) causing subsequent tissue damage and dysmorphogenesis. To verify the primary target of DHA in vivo and to detect consequences induced by early damage on embryo development, pregnant female rats were orally treated on gestation days (GD) 9.5 and 10.5 with 7.5 or 15 mg/kg/day DHA and caesarean sectioned on GD11.5, 12.5, 13.5, 15 and 20. A parallel in vitro WEC study evaluated the role of oxidative damage and examined blood islands and primitive RBCs. In accordance with the WEC results, primitive RBCs from yolk sac hematopoiesis were the target of DHA in vivo. The resulting anemia led to cell damage, which depending on its degree, was either diffuse or focal. Embryonic response to acute anemia varied from complete recovery to malformation and death, depending on the extent of cell death. Malformations occurred only in litters with embryonic deaths. DHA induced low glutathione levels in RBCs, indicating that oxidative stress may be involved in artemisinin toxicity; effects were extremely rapid, with altered RBCs seen as early as GD10. In establishing the relevance of these findings to humans, one should consider differences in the development of rodents and humans. While yolk sac hematopoiesis occurs similarly in the two species, early placentation and extent of exposure differ. In particular, early hematopoiesis takes only 7 days in rats (during which RBCs expand in a clonal fashion) compared with 6 weeks in humans; thus the susceptible period in relation to the duration of exposure to an artemisinin-based treatment may be substantially different.

Abnormalities, Multiple↗
PubMed2006

Electrophoresis of proteins and DNA on horizontal sodium dodecyl sulfate polyacrylamide gels.

An inexpensive Plexiglas apparatus which allows a simple and rapid preparation of horizontal polyacrylamide gels of different dimensions for different purposes, is described. Preparation of such gels is as easy and rapid as agarose gel preparation, and polymerized polyacrylamide gels are used to fractionate proteins or small DNA fragments using a common horizontal electrophoretic tank. This apparatus was used to electrophoretically fractionate proteins or DNA for immuno-blot analyses, particularly in the study of the allergenic response to Parietaria judaica pollen in senescence, for Southern-blot hybridizations and in the study of DNA polymorphisms.

Journal Article↗
PubMed2006

Assemblage of novel release modules for the development of adaptable drug delivery systems.

The aim of this paper was to study the applicability of the release module assemblage technology for an adaptable control of drug delivery rate and site. The elementary release module was a swellable matrix having one base convex and the other concave, named Dome Matrix. The swelling and release behavior of the release module was studied. The presence of the convex and concave bases in the swellable matrix slightly changed the overall drug delivery kinetics exhibited by a flat base cylindrical matrix having the same weight and composition. The swelling and drug release of the individual bases of the matrix was also studied to investigate the effect of the surface shape. The concave, convex and flat bases exhibited different swelling and release kinetics. The convex base released drug at faster rate than the concave base, whereas the flat base was intermediate. The release mechanisms of convex and concave bases were significantly different. The Dome Matrix module was selected for assembling several modules in a delivery system obtained by a guided insertion of the convex base into the concave base or by concave/concave base sticking. The module assemblage shows different drug release behavior depending on the geometry of assembled systems.

Delayed-Action Preparations↗
PubMed2006

The effect of residual water on antacid properties of sucralfate gel dried by microwaves.

The aim of this work was to study the acid neutralization characteristics of microwave-dried sucralfate gel in relation to the water content and physical structure of the substance. Several dried sucralfate gels were compared with humid sucralfate gel and sucralfate nongel powder in terms of neutralization rate and buffering capacity. Humid sucralfate gel and microwave-dried gel exhibited antacid effectiveness. In particular, the neutralization rate of dried gel powders was inversely related to the water content: as the water content of dried powders decreased, the acid reaction rate linearly increased. The relationship was due to the different morphology of dried sucralfate gels. In fact, the porosity of the dried samples increased with the water reduction. However, the acid neutralization equivalent revealed that the dried sucralfate gel became more resistant to acid attack in the case of water content below 42%. Then, the microwave drying procedure had the opposite effect on the reactivity of the aluminum hydroxide component of dried sucralfate gel powders, since the rate of the reaction increased whereas the buffering capacity decreased as the amount of water was reduced.

Antacids↗
PubMed2006

Prevalence of actinic keratoses and associated factors in a representative sample of the Italian adult population: Results from the Prevalence of Actinic Keratoses Italian Study, 2003-2004.

OBJECTIVE: The Prevalence of Actinic Keratoses Italian Study (PraKtis) was designed to estimate the point prevalence of actinic keratoses (AKs) and associated factors in a representative sample of the Italian adult population. DESIGN: A representative sample of people 45 years or older was selected from the electoral rolls according to a stratified random sampling design. SETTING: A total of 180 specifically trained interviewers contacted the sampled subjects and conducted face-to-face, computer-assisted interviews and skin assessments. PARTICIPANTS: A total of 12,483 subjects contacted and interviewed from March 1, 2003, through April 30, 2004. MAIN OUTCOME MEASURES: History of AKs and evidence of AKs at the interview. RESULTS: Overall, an estimated 34% of the Italian population reported ever having undergone a dermatological examination. A history of AKs was reported by 0.3% of the total sample. Topical therapy was the most popular treatment according to 39% of subjects, whereas 25% reported that they did not receive therapy. Based on the interviewer's judgment, the point prevalence of AKs was 1.4% (95% confidence interval, 1.2%-1.8%). Forty-two percent of people with AKs were unaware of their condition. The prevalence was higher among men than women and increased steadily with age. The prevalence increased with lighter phenotype and with more severe facial wrinkling. It also increased with the reported number of hours spent in the sun during the week and on holidays. No clear variation was observed according to the reported use of sunscreens. Lesions were usually multiple (median number, 4). There was a strong association between a history of nonmelanoma skin cancers and the presence of AKs (odds ratio, 4.5; 95% confidence interval, 1.8-11.0). CONCLUSIONS: The prevalence of AKs in our study was remarkably lower than expected based on data from the United States and Australia; in Italy, AKs seem to be underdiagnosed and undertreated.

Age Factors↗
PubMed2006

Primary microparticles and agglomerates of morphine for nasal insufflation.

The aim of this work was to study the characteristics of powders of morphine HCl suitable for nasal administration to be employed for pain treatment as alternative to injection. Primary microparticles of morphine were prepared by spray drying of aqueous drug solutions using sugars or sugar derivatives as drying protectors and particle shapers. The spray drying procedure modified morphine crystallinity making the substance amorphous and affecting its stability in dependence on the excipient employed. A tendency of the spray-dried powders to turn to varying degrees of yellow was observed. Tumbling the powder in a rotating pan allowed the agglomeration of the primary microparticles. Agglomerates were also obtained by tumbling a mixture of morphine crystals and spray-dried microparticles of excipients, with advantages for the stability of the preparation. A nasal device quantitatively insufflated all the morphine agglomerates. The in vitro transport of morphine through rabbit nasal mucosa was faster using nasal powders than with the saturated solution of morphine. Lactose was the most effective excipient for agglomerate manufacturing and delivery of spray-dried morphine. The agglomerates of morphine crystals mixed with mannitol/lecithin microparticles showed superior stability. However, the drug permeation through rabbit mucosa was slower than with spray-dried morphine microparticle agglomerates.

Administration, Inhalation↗
PubMed2006

Prevalence of smoking and attitude towards smoking regulation in Italy, 2004.

AIMS AND BACKGROUND: To update trends in smoking prevalence in Italy to 2004, and describe the attitudes towards forthcoming regulation of smoking. METHODS: Population-based face-to-face survey conducted in March-April 2004 on a sample of 3050 individuals (1509 men and 1541 women) aged 15 or over, representative of the general adult Italian population in terms of age, sex, geographic area, habitat, education and working status. RESULTS: Overall, 26.2% of the Italians aged 15 or over described themselves as current cigarette smokers (30.0% of men, 22.5% of women); 19.1% of men and 11.2% of women smoked 15 or more cigarettes per day. Ex-smokers were 17.9% (24.8% of men, 11.2% of women). The difference in smoking prevalence between men and women was greater in the elderly. More educated men, and those residing in northern Italy were less frequently current smokers. Conversely, women with a low level of education (19%) were less frequently current smokers than those with higher education (24%). More than 85% of Italian adult population were in favour of restrictions of smoking in public places, such as cafes and restaurants, and to ban smoking in workplaces. CONCLUSIONS: Self-reported smoking prevalence is decreasing in men but not in females. There is widespread support for smoking restriction in public areas.

Adolescent↗
PubMed2006

An in-frame complex germline mutation in the juxtamembrane intracellular domain causing RET activation in familial medullary thyroid carcinoma.

Activating mutations of the RET proto-oncogene are associated with inherited syndromes, multiple endocrine neoplasia (MEN2A/2B) and with familial and sporadic medullary thyroid cancer (MTC). Single base pair missense mutations in the extracellular Cys-rich domain are responsible for most MEN2A and familial MTC (FMTC) cases. Rarely, somatic deletions and germline duplications have been described in sporadic MTC and in FMTC. We report the detection and functional studies of a deletion/insertion in exon 11 (c.2646delGinsTTCT) associated with FMTC. This in-frame complex rearrangement leads to an Asn to Lys change (Lys666Asn) and to a Ser insertion. The mutation was found in the proband, who was diagnosed with metastatic MTC at 41 years, and in her son, who presented diffuse C-cells hyperplasia at 4 years of age. The mutation displayed a transforming activity stronger than Ret wild type (Ret-WT) at the focus formation assay and functional analyses after transient and stable transfection revealed an increased autophosphorylation, indicating the constitutive activation of the receptor. The transforming activity may be favoured by an increased stabilization of the fully mature form of the mutant receptor. Dimerization assay demonstrated that the activation mechanism of the complex mutation is not mediated by stable dimer formation. Computational analysis predicted nonconservative alterations in the mutant protein consistent with a possible modification of the conformation of the receptor. In conclusion, the first molecular studies on a complex germline RET mutation lying in the juxtamembrane region of the receptor are reported. Functional analyses showed that alterations at this level too can lead to a ligand independent Ret activation.

Adult↗
PubMed2005

Channels of cigarette distribution, price and tobacco consumption in Italy.

BACKGROUND: Limited information is available on the role of smuggling and of perceived influence of cigarette price on tobacco consumption in Italy. To elucidate the issues, we included specific questions in a survey on smoking in Italy. METHODS: Between March and April 2004, we conducted a survey on 3050 individuals aged 15 or over, representative of the general adult Italian population. The questionnaire included the estimate of the role of various channels of cigarette distribution and information on the self-reported perception of influence of prices on cigarette consumption in the young. RESULTS: Among current smokers, 85.6% bought cigarettes from tobacco shops, 7.5% from vending machines, and 6.9% from other channels of distribution, including smuggling, and internet (plus offered cigarettes). Overall, 35.9% of ever smokers (37.9% of males and 32.8% of females) reported that the prices had an intermediate to high influence on cigarette consumption in the young. Younger and less educated smokers were not more prone to report an influence of prices. CONCLUSIONS: These data indicate that in Italy smuggling now covers a limited proportion of cigarette sales, while cigarette prices have a substantial influence on tobacco consumption in the young.

Adolescent↗
PubMed2005

Mechanisms of formation and disintegration of alginate beads obtained by prilling.

In this paper, compendial sodium alginate beads have been manufactured by laminar jet break-up technology. The effect of polymer concentration, viscosity and polymeric solution flow rate on the characteristics of beads was studied. Size distribution of alginate beads in the hydrated state was strongly dependent on the flow rate and viscosity of polymer solutions, since a transition from laminar jet break-up conditions to vibration-assisted dripping was observed. The re-hydration kinetics of dried beads in simulated gastric fluid (SGF) showed that the maximum swelling of beads was reached after 1-2 h, with an increase in volume of two to three times and a time lag dependent on the polymer concentration. The re-hydration swelling profiles in simulated intestinal fluid (SIF) showed no time lag and higher swelling volume; moreover, in this medium after the maximum swelling was reached, the bead structure was quickly disaggregated because of the presence in the medium of phosphate able to capture calcium ions present in the alginate gel structure.

Alginates↗
PubMed2005

Release and permeation kinetics of caffeine from bioadhesive transdermal films.

The aim of this work was to investigate, in vitro, the kinetics of release and permeation of caffeine, chosen as model drug, from bioadhesive transdermal films. These films are not self-adhesive but become adhesive when applied to wet skin. Permeation experiments were performed from films with different drug loadings using rabbit ear skin as barrier. In order to characterize the release kinetics of caffeine from the film, a polyethylene membrane, impregnated with isopropyl myristate was employed. The data obtained in the present work suggest that caffeine release from transdermal bioadhesive films was controlled either by the permeability characteristics of the skin or by the film itself, depending on drug loading. When drug loading is low (ie, caffeine is dissolved in the polymers constituting the film), the control resides in the skin. When caffeine loading exceeds its solubility in the film, the permeation profile is not linear, but shows a sort of burst effect in the early times of permeation, probably owing to the presence of solid drug and/or to a certain degree of "conserved supersaturation" in the solid phase.

Adhesives↗
PubMed2005

Silicon oxycarbide glasses for blood-contact applications.

Silicon oxycarbide (SiOxCy) glass compositions are shown to exhibit a variable propensity to contact activate coagulation of whole human blood plasma that depends on X:Y surface stoichiometry. SiOxCy exhibit activation properties similar to pyrolytic carbon (PC) over a broad range of X:Y ratios. Surface composition of SiOxCy glass powders prepared by pyrolysis of thermosetting polysilsequioxanes roughly correlated with total carbon concentration of precursor resins and could be significantly modified by etching in alkaline solutions. Results suggest that SiOxCy may offer unique properties as a substitute for PC in medical-device applications demanding excellent tribological properties, such as artificial heart valves.

Biocompatible Materials↗
PubMed2005

Effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos in vitro.

Artemisinin derivatives are not currently recommended for use during the first trimester of pregnancy because they cause embryo death and some abnormalities in early pregnancy in animals. We studied the effects of dihydroartemisinin (DHA) in rat whole embryo cultures (WEC). DHA was added to the culture medium for the entire 48-h culture, 1.5 h at the beginning or at the end of the culture at 0.01-2 microg/mL. DHA affected primarily red blood cells during yolk sac hematopoiesis. Higher concentrations and longer exposure inhibited angiogenesis. Tissue damage (cell deaths) and effects on embryo morphology (neural tube, branchial arches, somites and caudal region defects) were attributed to these events. The viability of severely affected embryos beyond the 48-h assay is uncertain. These results help explain findings from animal data and provide evidence that the yolk sac is highly susceptible to artemisinin compounds. Extrapolating results to pregnant women exposed in the first trimester remains difficult. Pharmacovigilance and further studies of the mechanism of damage are needed.

Animals↗
PubMed2005

Impact of a major thermoelectric plant on self-perceived health status.

BACKGROUND: Measuring self-perceived health status and risk perception according to environmental factors remains a major open issue with important health policy implications. METHODS: To measure self-perceived health status in an area where a major thermoelectric plant has been active since 1994, in October 2001, we conducted a two sample survey using the SF-12 Health Survey. The study sample (2001 individuals) representative of the population living in the plant area (Montalto di Castro, Central Italy) was compared with a random sample of the general Italian population (1928 individuals). Mean values were adjusted for age, sex and education. RESULTS: SF-12 summary scales means are comparable in both samples: 50.2 (SE: 0.3) versus 49.9 (SE: 0.3) for the physical score, and 47.7 (SE: 0.4) versus 48.7 (SE: 0.4) for the mental score for Montalto di Castro area and Italian sample respectively. CONCLUSION: People living near a major thermoelectric plant have a subjective health status comparable to that reported by the general Italian population.

Adolescent↗
PubMed2005

Effect of residual water content on the physico-chemical properties of sucralfate dried gel obtained by microwave drying.

The purpose of this study was to investigate the physico-chemical characteristics of sucralfate humid gel dried by microwaves, in relation to the residual water content. Differential scanning calorimetry (DSC) allowed for the determination of the water state in sucralfate samples. Fourier-transform infrared (FT-IR) spectroscopy was used to monitor the changes in sucralfate gel structure induced by the microwave drying. A boundary value of total water content for sucralfate gel samples was found at 42% (w/w). Below this value only bound water was present, whereas above this value, the increase in total water was due to free water. In the physical form of gel, the strength of the coordination between sulfate anions and the positively charged aluminum hydroxide was dependent on the residual water content. The study of the sedimentation behavior of water suspensions prepared with dried sucralfate allowed for the evaluation of the retention of gel properties. We found that the microwave drying process affected the sedimentation of sucralfate dried gel suspensions independent of the residual water content: when suspensions were prepared from sucralfate dried gel powders containing more than 42% (w/w) of residual water, the sedimentation ratio was higher than 0.9. The non-gel powder suspension showed a sedimentation ratio of 0.68 +/- 0.02, whereas the sucralfate humid gel suspension did not sediment.

Anti-Ulcer Agents↗
PubMed2005

Metallic colloid nanotechnology, applications in diagnosis and therapeutics.

In recent years the fields of medicine and biology assist to an ever-growing innovation related to the development of nanotechnologies. In the pharmaceutical domain, for example, liposomes, polymer based micro and nanoparticles have been subjects of intense research and development during the last three decades. In this scenario metallic particles, which use was already suggested in the first half of the '80, are now experiencing a real renaissance. In the field of diagnosis, magnetic resonance imaging is one of the first and up to now the most developed application of metallic particles. But beside this application, a very new generation of biosensors based on the optical properties of colloidal gold and fluorescent nanocrystals, called quantum dots seems to be ready to be implemented in diagnosis and medical imaging. Concerning therapeutic applications, the potentialities of metal nanoparticles to help fulfilling the need of time and space controlled release of drugs has been intuited for a long time. Nowadays, magnetically guided carriers or thermal responsive matrices, in which drug release is triggered by the heating of metal nanoparticles, are effective examples of their application in drug delivery, while more recently efforts to develop metallic nanoobjects to be used as vectors of nucleic acids for vaccination and transfection have been multiplied. In the future, one of the most interesting challenges is certainly the use of metallic nanoparticles for an innovating, effective and selective physical treatment of solid tumors via targeted intracellular hyperthermia.

Animals↗