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Biomedical subjects

G Micali

Publications and source records attributed to G Micali.

At least 19 recordsLinked to original sources
PubMed2001

Induction of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: regulation by a natural antioxidant from rosemary extract.

Reactive oxygen species have been implicated in the pathogenesis of the severe connective tissue damage present in several photodermatologic disorders, including drug-induced phototoxicity, porphyrias and photoaging. Oxidative stress has been shown to alter the expression of mammalian antioxidant enzymes and to enhance numerous transcription factors, including nuclear factor-kappa B, stress-activated protein kinase and heat shock factor. The latter represents the transcription factor for the synthesis of cytoprotective proteins called heat shock proteins. In this study, we investigated the role of oxidative stress and sulfdryl (SH) groups in the induction of HSP70 in human skin fibroblasts and the effect of antioxidants. We found that significant HSP70 induction occurred after exposure to HOOH and this was associated with marked perturbation in protein and nonprotein SH groups and with a considerable increase in protein carbonyl levels. Treatment with a natural antioxidant from rosemary extract provided notable protection against stress-induced modifications of cellular SH and carbonyl content, maintaining functional levels of cytoprotective heat shock protein 70. Our results point to the possible involvement of redox mechanisms in the heat shock signal transduction pathway, which may play an important regulatory role in the genetic mechanisms of tolerance to oxidative stress. Exogenous supplementation of an antioxidant hydrophilic extract from rosemary could have cosmetic benefits and may represent an efficient tool to minimize free radical-induced skin damage.

Antioxidants↗
PubMed1999

The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin.

BACKGROUND: Cell therapy is an emerging therapeutic strategy aimed at replacing or repairing severely damaged tissues with cultured cells. Epidermal regeneration obtained with autologous cultured keratinocytes (cultured autografts) can be life-saving for patients suffering from massive full-thickness burns. However, the widespread use of cultured autografts has been hampered by poor clinical results that have been consistently reported by different burn units, even when cells were applied on properly prepared wound beds. This might arise from the depletion of epidermal stem cells (holoclones) in culture. Depletion of holoclones can occur because of (i) incorrect culture conditions, (ii) environmental damage of the exposed basal layer of cultured grafts, or (iii) use of new substrates or culture technologies not pretested for holoclone preservation. The aim of this study was to show that, if new keratinocyte culture technologies and/or "delivery systems" are proposed, a careful evaluation of epidermal stem cell preservation is essential for the clinical performance of this life-saving technology. METHODS: Fibrin was chosen as a potential substrate for keratinocyte cultivation. Stem cells were monitored by clonal analysis using the culture system originally described by Rheinwald and Green as a reference. Massive full-thickness burns were treated with the composite allodermis/cultured autograft technique. RESULTS: We show that: (i) the relative percentage of holoclones, meroclones, and paraclones is maintained when keratinocytes are cultivated on fibrin, proving that fibrin does not induce clonal conversion and consequent loss of epidermal stem cells; (ii) the clonogenic ability, growth rate, and long-term proliferative potential are not affected by the new culture system; (iii) when fibrin-cultured autografts bearing stem cells are applied on massive full-thickness burns, the "take" of keratinocytes is high, reproducible, and permanent; and (iv) fibrin allows a significant reduction of the cost of cultured autografts and eliminates problems related to their handling and transportation. CONCLUSION: Our data demonstrate that: (i) cultured autografts bearing stem cells can indeed rapidly and permanently cover a large body surface; and (ii) fibrin is a suitable substrate for keratinocyte cultivation and transplantation. These data lend strength to the concept that the success of cell therapy at a clinical level requires cultivation and transplantation of stem cells. We therefore suggest that the proposal of a culture system aimed at the replacement of any severely damaged self-renewing tissue should be preceded by a careful evaluation of its stem cell population.

Adolescent↗
PubMed1999

Penile cancer among patients with genital lichen sclerosus.

BACKGROUND: Genital lichen sclerosus (LS) has sporadically been reported to be associated with penile squamous cell carcinoma (SCC). OBJECTIVE: The purpose of this study was to assess the risk of malignant degeneration in a series of male patients affected by genital LS. METHODS: All cases of histologically proven epithelial malignancy associated with penile LS recorded in our pathology files over a 10-year period (1987-1997) were reviewed. Assessment for presence of human papillomavirus (HPV) was performed from paraffin-embedded tissues using polymerase chain reaction (PCR). RESULTS: Five of 86 white and uncircumcised men with genital LS (mean age at diagnosis, 53 years; range, 22-83 years) showed malignant or premalignant histopathologic features: 3 had SCC, one had erythroplasia of Queyrat (unifocal SCC in situ), and one verrucous carcinoma. The average lag time from onset of LS was 17 years (range, 10-23 years). Histologically, transition from LS to frank neoplastic foci was evident in all cases of SCC. In these SCC cases, areas of epithelial dysplasia were well evident at the tumor periphery. In the remaining cases, the histologic findings were consistent with erythroplasia of Queyrat and verrucous carcinoma. PCR detected HPV 16 infection in 4 of the 5 cases; one SCC patient was negative for HPV. CONCLUSION: Malignant changes were associated with 5.8% of the cases of penile LS in our series. Therefore patients with genital LS are at considerable risk of the development of penile SCC, as well as other epithelial and in situ carcinomas, namely verrucous carcinoma and erythroplasia of Queyrat. HPV infection probably plays a major role because 4 of 5 patients were positive for HPV. Histologically, epithelial dysplasia may represent a precancerous stage before the development of neoplasia in atrophic nonproliferative LS lesions, as its presence at the tumor periphery in our SCC biopsy samples seemed to suggest.

Adult↗
PubMed1999

Increased risk of erythema multiforme major with combination anticonvulsant and radiation therapies.

Erythema multiforme major (EMM; Stevens-Johnson syndrome) is a cutaneous disorder associated with a wide variety of factors including ingestion of drugs such as phenytoin and exposure to intracranial radiation therapy. Based on observations of a 47-year-old black man with brain metastases who developed EMM after combined phenytoin and radiation therapy, we conducted a MEDLINE literature search for articles on similar cases from 1966 to the present. Twenty cases were identified that support the hypothesis that EMM is associated with combined phenytoin and radiation therapy. The reaction, or its severity, has no relationship to the phenytoin or radiation therapy dosage, or to the histologic type of brain tumor. Also, EMM has no apparent age or gender predisposition in association with phenytoin-radiation therapy. Thus this is a clinical phenomenon that occurs with unusual frequency in patients with brain tumor who undergo radiation therapy while taking phenytoin. Phenytoin and other anticonvulsants such as phenobarbital and carbamazepine induce cytochrome P450 3A and produce oxidative reactive intermediates that may be implicated in hypersensitivity reactions such as EMM. Both carbamazepine and barbiturates have shown cross-sensitivity with phenytoin; furthermore, a case of EMM in a patient receiving carbamazepine and whole brain radiation therapy has been reported. As carbamazepine, valproate, and barbiturates have been associated with EMM, gabapentin may be considered as alternative anticonvulsant therapy when appropriate.

Adult↗
PubMed1998

Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily.

BACKGROUND: The purpose of this study was to examine the clinical and epidemiologic features of pemphigus in eastern Sicily. METHODS: All new cases of pemphigus seen in the Dermatology Clinic at the University of Catania during the period January 1982 to June 1996 were studied retrospectively. RESULTS: Eighty-four patients with pemphigus represented 1.3% of 6653 patients admitted to our clinic in a 13.5-year period, with an average annual incidence of six cases per year. The most common form of presentation was pemphigus vulgaris (PV) (75%), followed by pemphigus erythematosus (17%), pemphigus herpetiformis (6%), and pemphigus vegetans (2%). In 6% of PV patients, the oral lesions were not followed by skin involvement, and the lag time between the onset of illness and the final diagnosis in five PV cases was prolonged, ranging from 4 to 7 years, probably due to the mild clinical presentation of the disease. Two trauma-related PV cases were documented; in one case, the blisters were located in a surgical scar and in the other in a burn scar. CONCLUSIONS: Our findings showed that pemphigus has a relatively high prevalence in eastern Sicily compared with other Italian regions; PV is the most common variant, and may have a mild course not always requiring aggressive therapy.

Adult↗
PubMed1998

Increased burn patient survival with once-a-day high dose teicoplanin and netilmicin. An Italian multicenter study.

This is the final report of a large, controlled, multicenter Italian study on immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of total body surface area (mean 35%). The antibiotic treatment of burn patients consisted of topical silver sulfadiazine, short-term antimicrobial chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300 mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients received thymostimulin, 70 mg i.m. qd for the first month and every other day thereafter. The analysis at completion of 634 valid cases showed that when the results are stratified by means of the Roi risk index, 396 of the 530 patients who contracted wound infection (84%) after chemoprophylaxis were in the first three categories and a mean of 95% survived. Of the remaining 134 patients (Roi index 4-5) only 50% survived. There was no difference in survival of the immunotherapy group in comparison with the parallel group without thymostimulin. The short-term antimicrobial prophylaxis prevented wound infection in only 104 of 634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial pathogens involved in septic complications Staphylococcus aureus and Pseudomonas aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and clinical cure or improvement were seen with combination chemotherapy in 64% of all patients, mainly with only one treatment cycle. This value increased to 79% for the 395 protocol-complying patients and went down to 20% in the 135 non-compliers. The total survival of complier and non-complier patients was 447 of the 530 valid patients (84%). The overall mortality of the 634 evaluable patients was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly proportional to the percentage of burned body surface area, to increasing age and other variables of the Roi index, a 50% mortality being associated with a 72.5% total body surface area burned. Normoergic burn patients had a mortality rate of 9.1% versus 35.7% in anergic patients.

Adolescent↗
PubMed1998

Transient leucoderma appearing in an untreated area following contact immunotherapy for alopecia areata.

One of the possible unwanted side effects following contact immunotherapy of alopecia areata is skin hypopigmentation, either in the form of a transient, post-inflammatory hypopigmentation or as the development of a persistent, depigmented patch. A case of leucoderma occurring on the forehead of a 16-year-old girl following application of squaric acid dibutylester to the scalp for the treatment of alopecia areata is described. Past medical and family history were negative for vitiligo and autoimmune disorders. The hypopigmented patch was distant from the scalp area where squaric acid dibutylester had been applied, and it was not preceded by any sign of eczema, erythema or itch in the same area. Moreover, it faded as soon as treatment was discontinued. A 4-year follow-up revealed no evidence of vitiligo. In conclusion, the possible occurrence of a transient leucoderma in untreated areas should be included among the side effects of contact immunotherapy of alopecia areata with squaric acid dibutylester.

Adolescent↗
PubMed1997

Myofibroblasts of palmar fibromatosis co-express transforming growth factor-alpha and epidermal growth factor receptor.

Several studies have shown that different growth factors are involved in the pathogenesis of palmar fibromatosis. The aim of the present study was to investigate whether transforming growth factor alpha (TGF-alpha) and its cellular receptor, epidermal growth factor receptor (EGF-R), are expressed in palmar fibromatosis. Nodules from 20 patients with palmar fibromatosis and control normal palmar fascias were studied by the reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR followed by Southern blotting demonstrated that palmar fibromatosis nodules contained high levels of TGF-alpha and EGF-R messenger RNA (mRNA) transcripts, while normal fascias showed only low levels. Depending on the degree of cellularity and fibrosis, the three following histological phases were recognized in palmar fibromatosis nodules: proliferative, involutional, and residual. Immunohistochemistry, using alpha-smooth muscle actin as a cellular marker for myofibroblasts, revealed that TGF-alpha and EGF-R are co-expressed by myofibroblasts in the highly cellular areas of both proliferative and involutional phases, while they are absent or only focally detectable in the fibroblasts of normal fascia and in hypocellular and fibrotic areas of both involutional and residual phases. The restricted co-expression of TGF-alpha and EGF-R to myofibroblasts, the proliferating cellular component of nodules, suggests that an autocrine and/or juxtacrine growth stimulation by TGF-alpha via the EGF-R may be involved in the pathogenesis of palmar fibromatosis.

Actins↗
PubMed1997

Determination and correlation of in vitro viability for hairless mouse and human neonatal whole skin and stratum corneum/epidermis.

BACKGROUND AND DESIGN: Viable tissue is essential to assess the rate and extent of biotransformation during percutaneous absorption in vitro. We assessed the viability of hairless mouse whole skin (WS) and stratum corneum/epidermis (SCE) and human neonatal SCE following separation from the dermis by EDTA phosphate-buffered saline (EDTA-PBS) incubation or by heat treatment by measuring the conversion of dextrose to lactate. Lactate concentrations in receptor fluid samples were determined using a Sigma diagnostic lactate determination kit. A standard curve was prepared and samples assayed spectrophotometrically at 340 nm using a lambda 2 beta spectrophotometer. Standard curves were prepared for each experiment and correlation coefficient values (r) were calculated. RESULTS: Our results showed that hairless mouse SCE was associated with glucose conversion to lactic acid at an increased rate if incubated in EDTA-PBS for 4 h and used immediately. Lactate production was greater with the dermis present (EDTA-PBS WS). The rate of glucose to lactate conversion in hairless mouse SCE was 20-25% of that found in WS. Compared with Dulbecco's modified PBS (DMPBS)-treated WS controls, the rate of lactate production in EDTA-PBS-treated WS was nearly a 50% less. Heat treatment in water at 60 degrees C to separate SCE from hairless mouse WS appeared to eliminate viability. Viability of hairless mouse SCE, as measured by glucose conversion to lactate, was comparable to human neonatal SCE. CONCLUSIONS: These results suggest that the dermis is a significant contributor to glucose metabolism and that incubation in EDTA-PBS is a contributing factor to the overall decrease in metabolic capacity of the tissue. As a result of these findings, hairless mouse SCE appears to be useful as a model for human neonatal SCE in percutaneous absorption studies.

Animals↗
PubMed1996

High-performance liquid chromatographic determination of the biologically active principle hypericin in phytotherapeutic vegetable extracts and alcoholic beverages.

Hypericin was determined using an RP C18 (3 microns) column 8.3 x 0.4 cm I.D.), thermostated at 50 degrees C. The separation was achieved with programmed elution using phosphate buffer (pH 7)-methanol (3:7) and watermethanol (3:7) as eluents. Fluorimetric detection was carried out with excitation at 470 nm and emission at 590 nm. The analytical sample was prepared by simple dilution in methanol of the phytotherapeutic extract or of the alcoholic beverage. Hypericin can be rapidly and accurately determined at concentrations down to 0.1 mg/kg without any interferences.

Alcoholic Beverages↗