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Biomedical subjects

A Colasanti

Publications and source records attributed to A Colasanti.

At least 19 recordsLinked to original sources

Substance abuse in first-episode schizophrenic patients: a retrospective study.

Several studies suggest a high comorbidity of substance abuse and schizophrenia, associated with higher frequency of relapse, more positive symptoms and depression, cognitive impairment, poorer outcome and treatment response. A high incidence of substance abuse is also observed in first-episode patients. Among patients with substance abuse, the onset precedes the onset of psychosis of several years in most cases. All the patients with a first episode of schizophrenia, at first admission to the Psychiatric Service of Diagnosis and Treatment of Ospedale Maggiore of Milan during the years 1990 to 2004, have been included in our study.The clinical evaluation has been obtained considering the following items of Brief Psychiatric Rating Scale (BPRS): conceptual disorganization, depressed mood, hostility, hallucinations, unusual content of thought.The results showed that 34.7% of first-episode schizophrenic patients had a lifetime history of substance abuse. The age of onset of schizophrenia is significantly lower for drug abusers than for patients without any type of abuse and for alcohol abusers (p < 0.005). In multi drug abusers, cannabis resulted the most frequently used (49%), followed by alcohol (13%), and cocaine (4%). Substance abusers have obtained a significant higher score in "thought disturbance" item (p < 0.005) and in "hostility" item (p < 0.005) compared to non substance abusers. Non drug abusers showed lower mean scores of "hostility" item compared to cocaine abusers and multi drug abusers (p < 0.005). Our findings seem to indicate that substance abuse in the early course of illness determines an earlier onset of schizophrenia and increases severity of some psychotic symptoms like "hallucination" and "unusual content of thought". Therefore persons incurring a risk of schizophrenia may be warned of the possible relation between substances and psychosis and have to be counselled against the use of them.

Journal Article↗

Photodynamic therapy with topical delta-aminolaevulinic acid for the treatment of plantar warts.

Treatments currently employed for plantar warts are often painful (electrosurgery, cryotherapy) and not always effective (keratolytic agents). In this paper we investigate the effect of photodynamic therapy (PDT) with topical delta-aminolaevulinic acid (ALA) on plantar warts. In order to remove the superficial hyperkeratotic layer of the warts an ointment containing 10% urea and 10% salicylic acid was applied for 7 days. After gentle curettage, a cream containing 20% ALA was applied under an occlusive dressing for 5 h on 64 warts, while 57 warts (controls) received only the vehicle. Both the ALA-treated warts and the controls were irradiated using a visible light lamp (with a range of 400-700 nm, peaking at 630 nm). The light dose was 50 J/cm(2). Patients were followed-up for 22 months. Two months after the last irradiation session 48 (75.0%) out of 64 ALA-PDT treated warts had resolved. By contrast only 13 (22.8%) of the 57 control warts had done so. During the treatment a few patients complained of a mild burning sensation. The absorption of ALA by the verrucous tissue was demonstrated by in vivo fluorescence spectroscopy. This study shows that topical ALA-PDT can be an alternative treatment for plantar warts. Further studies will be necessary in order to optimize the concentration of ALA and duration of treatment.

Administration, Topical↗

[Disseminated intravascular coagulation in chickenpox. Report of a case in a child].

The case of a healthy and immunocompetent five-year-old boy, who developed a disseminated intravascular coagulation during chickenpox is described. Disseminated intravascular coagulation manifestations were extremely severe and included macroscopic hematuria, necrotic purpura and cerebrovascular thrombosis. The outcome in this patient was a complete recovery. Nevertheless, the possibility of a seriously complicated course of chickenpox even in low-risk children subgroups suggests that the Varicella-Zoster virus infection should not be underestimated. More accurate information about the impact of chickenpox and its complications on the population is needed, in order to provide a contribution for the debate about the costs associated with this disease and the potential benefits of both the early antiviral therapy and the vaccinal prophylaxis.

Acute Disease↗

MS-2 fibrosarcoma characterization by laser induced autofluorescence.

BACKGROUND AND OBJECTIVE: MS-2 fibrosarcoma implanted in BALB-CDF1 mice was investigated by frequency and time domain measurements of the autofluorescence (AF) radiation emitted upon excitation by a N(2) laser beam (337.1 nm). STUDY DESIGN/MATERIALS AND METHODS: AF spectra were obtained by using a spectrograph, a multichannel plate and an optical multichannel analyzer for the steady state detection. Time-resolved spectra were performed by means of a monochromator, a photomultiplier, and a digital signal analyzer. RESULTS: Spectral measurements show that the autofluorescence intensity of pathologic tissue is lower than that of healthy one in the 400- to 500- spectral region. In the same spectral range, we found the fluorescence decay to be the sum of a fast and a slow component. The lifetime of the fast component of tumoral tissue is significantly lower than that of healthy samples. CONCLUSION: Frequency and time domain measurements used in combination show that MS2-fibrosarcoma is characterized by the probable presence of the free form of NADH.

Animals↗

Hypericin photosensitization of tumor and metastatic cell lines of human prostate.

We have investigated the photoactivating effect of hypericin on two cancer cell lines: PC-3, a prostatic adenocarcinoma non-responsive to androgen therapy and LNCaP, a lymphonodal metastasis of prostate carcinoma responsive to androgen therapy. The two cell lines are incubated for 24 h with hypericin at concentrations ranging from 0.001 to 0.3 microg/ml in cell culture medium. The cells are irradiated at 599 nm (fluence = 11 J/cm2) using a dye laser pumped by an argon laser. Hypericin exerts phototoxic effects on both cell lines, while it does not produce toxic effects in the absence of irradiation. These results suggest that photodynamic therapy (PDT) with hypericin could be an alternative approach to the treatment of prostatic tumors, and could be beneficial in tumors that are non-responsive to androgen therapy.

Adenocarcinoma↗

In vitro photo-activation of newly synthesized chlorin derivatives with red-light-emitting diodes.

We investigated the in vitro photo-activation properties of two chlorin derivatives, i.e. 8-cis-heptylchlorin dicarboxylic acid and 3-trans-heptylchlorin bisamidoglucose derivative, which exhibit lipophilic properties similar to those of the active fractions of Photofrin II, on a normal epithelial cell line (FRTL-5). We used as an irradiation source an array of diodes emitting red light (lambda = 675 nm), which produced a fluence of 7mW cm-2 on the cells. We found that photo-activation with chlorin derivatives in the concentration range 1-100 ng ml-1 greatly enhanced the mortality of the irradiated cells (energy density, 0.25 J cm-2) with respect to the control cells kept in the dark. This response is immediate and appears to be an "all or none' effect. Taking into account that compounds exhibit a strong absorbance peak in the long wavelength region of visible light where tissues are relatively transparent, our results suggest that chlorins can be considered to be good candidates for application in photodynamic therapy.

Animals↗

[Orbital cellulitis. A case report].

This study describes the case of a 6 years old child, male, with orbital cellulitis and underlines the importance of an early diagnosis and therapy to avoid severe complications often present in this disease. Swelling and redness of the eyelid, pain and ophthalmoplegia are the first sign of an orbital cellulitis and they require rapid diagnostic procedure such as ultrasound and TC scan of the orbital region to evaluate the integrity of the profound orbital tissues. The child was admitted at the Department of Pediatrics, University "La Sapienza" of Rome and underwent an ultrasound, TC scan and serum exams which demonstrated the elevation of the sedimentation rate, reactive C protein and WBC plus the interesting of the profound orbital tissues. The child was treated with antibiotic and antiinflammatory therapy showing a complete recovery within 7 days. An ultrasound performed 7 days later demonstrated a complete resolution of the inflammatory process. In summary, this study would like to stress the necessity of an early diagnosis and an appropriate therapy in order to avoid the severe complications often present in children with orbital cellulitis.

Anti-Bacterial Agents↗

Targeted gene transfer in eucaryotic cells by dye-assisted laser optoporation.

The blue beam of an Argon laser (488 nm) has been focused on the cell membrane in the presence of phenol-red, an usual component of cell culture media, through a 100 x objective. At the site of the beam impact, due probably to local temperature changes, the cell membrane modifies its permeability. As a consequence of the hit, circular areas, whose radius may be apparently regulated by changing the irradiation time and/or the radiation intensity (energy), appear on the wall, last for a short time and fade spontaneously within 1-2 minutes. No evident sings of cell injury or hurt have been observed afterward. Plasmid DNA, purposely added to culture fluid, easily slips in the cytoplasm; utilizing such approach, thereafter indicated as "optoporation', we have successfully transfected two genes, namely beta-galactosidase and chloramphenicol-acetyl-transferase in murine NIH3T3 fibroblasts. Therefore optoporation represents an additional procedure for gene transfer with several advantages over already available methods: (1) it only takes advantage of the presence of phenol-red, a normal cell medium component, with no need of addition of extraneous substances; (2) it is a very mild treatment virtually suitable for any cell type and (3) it allows transfection of selected cells even in the presence of cells of different type (providing that they are morphologically distinguishable).

3T3 Cells↗

Kinetic transport analysis of daunorubicin by LoVo and LoVo/DX cells.

We describe a fluorometric technique for the measurement of transport parameters of fluorescent drugs through cellular membranes. Unlike other procedures, this method gives an accurate measure of drug accumulated in the cells and measures the fraction of free and bound drug in the cell. The kinetic parameters of transport through cellular membranes are determined using a simple three-compartment model combined with fluorescence measurements performed on the extracellular medium and on Triton-permeabilized cells during daunorubicin incorporation. With this technique we found that LoVo cells have a greater daunorubicin uptake, a similar input rate constant and a lower output rate constant than the drug-resistant LoVo/DX cells.

Antibiotics, Antineoplastic↗

Fluorochromes with long-lived fluorescence as potential labels for pulsed laser immunocytofluorometry: photophysical characterization of pyrene derivatives.

An apparatus for laser-induced time-resolved fluorescence measurements, in conjunction with pyrene derivatives endowed with long-lived excited singlet states, was employed for immunocytofluorometric measurements. N-(1-pyrene)maleimide, 1-pyrenesulfonyl chloride and 1-pyreneisothiocyanate were conjugated with immunoglobulin, antimouse-IgG, and the fluorescence decays of both free and conjugated forms were investigated. Bi-exponential decays were obtained in all cases with time constants of the short-lived component in the range 3-4.7 ns and the long-lived one in the range 20-55 ns. Only the spectral distribution of the two components is essentially affected upon conjugation. The persistence of the long-lived component, well above the lifetime of autofluorescence, and of the antibody specificity, as shown by immunodiffusion tests, upon conjugation indicates that this technique could be advantageously adopted in immunocytofluorometry.

Animals↗

Fluorometric determination of the kinetics of anthracyclines uptake by cells.

Fluorometric measurements on extracellular medium are shown to allow kinetic parameters of in vitro anthracycline uptake by cells to be calculated. The method provides influx and efflux rates, as well as the time dependence of both influx and efflux. It is applied to a normal thyroid epithelial cell line (FRTL-5) and a cell line (MPTK-6) derived from the lung metastases of a thyroid carcinoma exposed to daunorubicin at concentrations within the range of 250 to 1000 ng/ml. The results show that the number of cells influences the dependence of the kinetics upon the extracellular drug concentration and that the MPTK-6 cells are endowed with very efficient efflux mechanisms.

Animals↗

Laser photosensitization of cells by hypericin.

Administering a light dose of 90 J/cm2 at 599 nm during incubation with hypericin to a highly differentiated normal epithelial cell line (FRTL-5), derived from Fisher rat thyroid, and to a neoplastic cell line (MPTK-6), derived from the lung metastases of a thyroid carcinoma induced in Fisher rats, produces cell kill at drug doses 1000 times lower than those necessary to cause the same mortality in the dark. The photocytocidal activity of this polycyclic quinone drug on neoplastic cells is superior to that of antitumor anthraquinone drugs, such as daunomycin and mitoxanthrone, and to the photosensitized antiviral activity previously reported for hypericin.

Animals↗

Enhanced response to daunomycin of normal, tumor and metastatic cell lines via drug photoactivation.

We have compared the cytotoxicity of daunomycin in vitro to highly differentiated normal epithelial cells (Fisher rat thyroid cells, FRTL-5) and to two neoplastic cell lines, a thyroid carcinoma (TK-6) and its lung metastasis (MPTK-6). Whereas the cell lines are equally sensitive to the drug in the dark, if irradiated during incubation with daunomycin (86 J/cm2 at 488 nm), they become more and differently sensitive. Namely, the drug doses producing 50% mortality decrease by factors of about 22, 28 and 16 for FRTL-5, TK-6 and MPTK-6 cell lines, respectively. This result correlates with differences in drug uptake and resistance observed in the normal and neoplastic cell lines.

Animals↗

Excited singlet state properties of anthracenedione photosensitizers.

The absorption, fluorescence and S1 state kinetics of anthracycline antitumour drugs (e.g. daunomycin, adriamycin) and several imino- and/or amino-substituted derivatives are investigated. The study, which includes all anthracyclines which possess photocytocidal activity, is extended to the disubstituted aminoanthracenedione, mitoxantrone, a red-light-absorbing antitumour drug whose activity, both in vitro and in vivo, is enhanced by photoactivation. The S1 state of the anthracycline imino and amino derivatives, in aqueous buffer at pH 7.4, is characterized by bi-exponential decay kinetics which indicates the presence of two ground state populations differing in the extent of hydrogen bonding. The ammonium group of the sugar moiety of anthracyclines contributes to the quenching of the S1 state population through a prototropic mechanism.

Antibiotics, Antineoplastic↗

Enhancement of antitumor drug cytotoxicity via laser photoactivation.

We investigate the efficacy of daunomycin, some imino- and amino-substituted daunomycin analogues and the disubstituted aminoanthracenedione, mitoxantrone, in photosensitizing short-term cell kill upon irradiation in the long wavelength visible range, during incubation of Fisher rat thyroid cells with the drugs. While all compounds exhibit similar cytocidal effects on our cell line, in the absence of irradiation, administering 86 J/cm2 at wavelengths either coincident or close to drug absorption peaks causes greater enhancement in cell mortality for the 4-demethoxydaunomycin analogues than either the parent drug or its 5-imino-derivative. A lower enhancement is observed with mitoxantrone. In particular, C50 doses (i.e. concentrations that would kill 50% cells) as low as approximately 10(-9) M are found for both 6- and 11-amino 4-demethoxydaunomycin, compared with the values obtained in the absence of light, which are 2.59 x 10(-4) and 0.43 x 10(-4) M, respectively. Our previous studies of the photophysical and photochemical properties of the excited states of these drugs, and ESR and spin trapping studies of photosensitized generation of singlet oxygen, which were extended in this work to include mitoxantrone, indicate that the cytocidal effects proceed via type I rather than type II mechanisms.

Animals↗

Photocytotoxicity of anthracyclines upon laser excitation in their long-wavelength absorption bands.

Newly synthesized daunomycin derivatives with red-shifted absorption compared to the parent molecule are shown to be able to photosensitize cells in vitro upon excitation with either argon or argon-pumped dye laser. Administering 86 J/cm2 total fluence (1 h irradiation) to Fisher rat thyroid cells during 2 h incubation with either daunomycin (excitation wavelength: 488 nm) or 5-iminodaunomycin (595 nm) produced cell killing at doses (about 2.7 X 10(-7) M for 50% cell survival) which were not toxic if administered in the dark. Greater photocytotoxicity (about 7 X 10(-8) M for 50% cell survival) was obtained with 4-demethoxydaunomycin as well as with its 6- and 11-amino derivatives (514 nm) while no cell killing as a result of photosensitization was observed for either Adriamycin or its 4'-iodo derivative. Our results suggest that the photosensitizing efficacy correlates with the absence of the methoxy group in the anthraquinone chromophore but is rather independent of the occurrence of triplet-mediated photoreactions. Finally, the fact that the imino- or amino-substituted 4-demethoxy compounds exhibit red-shifted absorption spectra compared to the parent molecule might be exploited for in vivo applications of the photoactivated cytotoxicity reported in this work.

Animals↗

Cell photosensitization by 5-iminodaunomycin activated with red light.

5-Iminodaunomycin, an anthracycline antitumor drug exhibiting an absorption peak at 595 nm, is shown to photosensitize in vitro cell kill. The photoactivation is performed irradiating the culture dishes during the incubation with the drug for 2 h with 34 mW/cm2 intensity, that is with light doses of up to 245 J/cm2. Long-term effects of administering 50 ng/ml and light for 2 h are studied in terms of growth curves. We show that photoactivation enhances the dark toxicity by a factor of about 10. Immediate cell death is produced by irradiating the cells in the presence of higher drug concentrations (e.g., 1000 ng/ml) which, however, are not toxic in the short term if administered in the dark. The viable cell percentage decreases at increasing light doses, being about 0.6% at the maximum dosage. Administering lower light doses, such as 30 J/cm2, which corresponds to an exposure duration of 15 min, has a short-term effect on the cell survival that strongly depends on the timing of the exposures within the incubation period.

Animals↗