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Biomedical subjects

R Caputo

Publications and source records attributed to R Caputo.

At least 55 records · Page 3Linked to original sources
PubMed1998

Mometasone furoate decreases adhesion molecule expression in psoriasis.

The topical corticosteroids are widely used in the treatment of moderate psoriasis, because of their usefulness for reducing inflammation and controlling itching. The therapeutic effect of corticosteroids in different cutaneous inflammatory diseases may be partially explained by their varying ability to block in vitro the synthesis of different cytokines, which play a pivotal role in epidermal hyperproliferation and leukocyte recruitment into the skin. The purpose of the present investigation was to further elucidate the mode of action of mometasone furoate, a medium-high potency, topical corticosteroid, on adhesion molecules, cytokines and cytokine receptor expression in psoriatic skin. Using an immunohistochemical assessment, we examined lesional skin biopsies from ten psoriatic patients before treatment and after 1 and 3 weeks of therapy. The overexpression of alpha 2, alpha 3, alpha 6, and beta 1 integrins detected in the spinous layer of untreated psoriatic skin was significantly decreased after therapy in 8 out of 10 cases, characterized by only partial clinical remission. In the remaining patients, a disappearance of the above integrin reactivity paralleling the disappearance of psoriatic lesions was induced by the treatment. With the exception of GM-CSF, no or only marginal effects of mometasone furoate on the cytokine and cytokine receptor system were observed. A significant reduction of the positive immunostaining with anti-ICAM-1 and ICAM-2 monoclonal antibodies on dermal vascular endothelial cells was also seen. Thus, our findings indicate that the therapeutic effects of mometasone furoate in psoriasis are mediated principally by decreasing adhesion molecule expression and to a lesser degree by inhibiting cytokine synthesis.

Administration, Cutaneous↗
PubMed1997

Synergistic inhibition of human cancer cell growth by cytotoxic drugs and mixed backbone antisense oligonucleotide targeting protein kinase A.

Protein kinase A type I plays a key role in neoplastic transformation, conveying mitogenic signals of different growth factors and oncogenes. Inhibition of protein kinase A type I by antisense oligonucleotides targeting its RIalpha regulatory subunit results in cancer cell growth inhibition in vitro and in vivo. A novel mixed backbone oligonucleotide HYB 190 and its mismatched control HYB 239 were tested on soft agar growth of several human cancer cell types. HYB 190 demonstrated a dose-dependent inhibition of colony formation in all cell lines whereas the HYB 239 at the same doses caused a modest or no growth inhibition. A noninhibitory dose of each mixed backbone oligonucleotide was used in OVCAR-3 ovarian and GEO colon cancer cells to study whether any cooperative effect may occur between the antisense and a series of cytotoxic drugs acting by different mechanisms. Treatment with HYB 190 resulted in an additive growth inhibitory effect with several cytotoxic drugs when measured by soft agar colony formation. A synergistic growth inhibition, which correlated with increased apoptosis, was observed when HYB 190 was added to cancer cells treated with taxanes, platinum-based compounds, and topoisomerase II selective drugs. This synergistic effect was also observed in breast cancer cells and was obtained with other related drugs such as docetaxel and carboplatin. Combination of HYB 190 and paclitaxel resulted in an accumulation of cells in late S-G2 phases of cell cycle and marked induction of apoptosis. A cooperative effect of HYB 190 and paclitaxel was also obtained in vivo in nude mice bearing human GEO colon cancer xenografts. These results are the first report of a cooperative growth inhibitory effect obtained in a variety of human cancer cell lines by antisense mixed backbone oligonucleotide targeting protein kinase A type I-mediated mitogenic signals and specific cytotoxic drugs.

Animals↗
PubMed1997

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Adapalene↗
PubMed1997

Severe self-healing nail dystrophy in a patient on peritoneal dialysis.

The unusual case of a patient on peritoneal dialysis who progressively developed onychodystrophy of the hands 2 months after Acinetobacter peritonitis had been reported. The nail disease consisted of acute pseudoclubbing, elkonyxis, severe Beau's lines and onychomadesis and showed spontaneous recovery within 4 months. Although reminiscent of severe Beau's lines and reflex sympathetic dystrophy, this observation shows a peculiar nail disorder of unknown cause.

Acinetobacter Infections↗
PubMed1997

Roaccutane treatment guidelines: results of an international survey.

BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of acne when it was introduced in 1982. METHODS: Twelve dermatologists from several countries with a special interest in acne treatment met to formally review the survey of their last 100 acne patients treated with oral isotretinoin. The primary purpose of the survey was to identify the types of acne patients who were prescribed oral isotretinoin and how the patients were managed. RESULTS: Of the 1,000 patients reviewed, 55% of those who received oral isotretinoin had those indications treated historically, i.e. severe nodular cystic acne or severe inflammatory acne, not responding to conventional treatment. Forty-five percent of patients who were prescribed oral isotretinoin however had either moderate or mild acne. Most patients in this group had moderate acne (85%). However, 7.3% had mild acne on physical examination. The criteria for prescribing oral isotretinoin in this less severe group of patients included acne that improves < 50% after 6 months of conventional oral antibiotic and topical combination therapy, acne that scars, acne that induces psychological distress and acne that significantly relapses during or quickly after conventional therapy. Treatment is usually initiated at daily doses of 0.5 mg/kg (but may be higher) and is increased to 1.0 mg/kg. Most of the physicians aimed to achieve a cumulative dose of > 100-120 mg/kg. Mucocutaneous side-effects occur frequently but are manageable while severe systemic side-effects are rarely problematic (2%). The teratogenicity of oral isotretinoin demands responsible consideration by both female patients and their physicians. Significant cost savings when treating acne patients with oral isotretinoin as compared to other treatment modalities were further proven in this study. CONCLUSIONS: Our recommendation is that oral isotretinoin should be prescribed not only to patients with severe disease but also to patients with less severe acne, especially if there is scarring and significant psychological stress associated with their disease. Acne patients should, where appropriate, be prescribed isotretinoin sooner rather than later.

Acne Vulgaris↗
PubMed1997

Ichthyosis congenita type IV: a new case resembling diffuse cutaneous mastocytosis.

The wide phenotypical heterogeneity within the ichthyosis congenita group of diseases is well known. We report a case of a very rare and unusual autosomal recessive ichthyosis congenita, type IV, according to the ultrastructural classification. Our case presented the triad clue for the diagnosis, characterized by follicular hyperkeratosis, prematurity and perinatal complications, but the clinical diagnosis was further complicated by hypereosinophilia and a strongly positive Darier's sign suggesting diffuse cutaneous mastocytosis. The diagnosis was provided only by electron microscopy, which showed the pathognomonic markers of ichthyosis congenita type IV, namely a large number of membrane structures in the stratum corneum and stratum granulosum. As a consequence, correct genetic counselling for the parents was carried out, and they were informed about the benign course of the disease after the complications of the perinatal period. This case is a further example of the reliability of ultrastructural markers in the diagnosis of inherited keratinization disorders, especially those with an unusual clinical appearance.

Humans↗
PubMed1997

Unique digital skin lesions associated with systemic sclerosis.

A 40-year-old woman with systemic sclerosis presented with multiple, large soft skin lesions with a cystic appearance over the interphalangeal joints of both hands. Aspiration of one of these lesions revealed the presence of a yellowish mucoid material which rapidly reappeared. Surgical dissection and excision of the masses was followed by recurrence a few months later. Pre-operative diagnosis was that of myxoid cysts, but the histological picture was reminiscent of cutaneous focal mucinosis, another form of primary mucinosis. The origin of these unique skin lesions is unclear, but speculation on a possible aetiological relationship between them and systemic sclerosis is presented.

Adult↗
PubMed1997

An evaluation of the allergic contact dermatitis potential of colloidal grain suspensions.

BACKGROUND: Colloidal grain suspensions have been used for decades as adjuncts in the treatment of atopic dermatitis, especially in the US. In Italy, many young children have been exposed to colloidal grains. Recently, it was suggested that these bath therapies may induce allergic contact dermatitis in some young atopic children. OBJECTIVE: To evaluate the allergic skin reactions to topical oat and rice colloidal grain suspensions of normal and atopic children with and without previous exposure to colloidal grain suspensions. METHODS: A double-blind, randomized patch study. Two concentrations of oat and rice colloidal grains (0.007% and 0.7%) were applied occlusively to the backs of 65 children living in Italy, ages 6 months to 2 years (43 were atopic and 22 were normal). RESULTS: There were neither immediate urticarial nor allergic reactions in any of the 65 study subjects, atopic or nonatopic; 5 of 43 (12%) atopic subjects developed irritant reactions to the test materials. Radioallergosorbent tests (RAST) tests were performed on 55 subjects. The negative RAST test results found in the nonatopic group correlated well with nonatopic status, but positive RAST tests were found in only 8 of 35 (23%) atopic dermatitis subjects. None of the sera from positive RAST scores corresponded to subjects with irritant patch reactions. CONCLUSIONS: The data indicate that topical colloidal grains can be used as an adjunct in the management of mild atopic dermatitis in children under 2 years of age. There was no evidence of sensitization to topical colloidal grains in the group studied.

Avena↗
PubMed1997

8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer.

8-Chloro-cyclic AMP (8-Cl-cAMP) is a cAMP analogue that specifically down-regulates type I protein kinase A, a signaling protein directly involved in cell proliferation and neoplastic transformation, and that causes growth inhibition in a variety of human cancer cell types. In this report, we have investigated the effects of 8-Cl-cAMP on the expression of several growth factors in human colon (GEO and LS174T) and breast (MDA-MB468) cancer cell lines. 8-Cl-cAMP treatment caused in the three cancer cell lines a significant dose- and time-dependent inhibition in the expression of various endogenous autocrine growth factors, such as transforming growth factor alpha, amphiregulin, and CRIPTO, and of two angiogenic factors, such as vascular endothelial growth factor and basic fibroblast growth factor, at both the mRNA and protein levels. Furthermore, 8-Cl-cAMP treatment markedly inhibited the ability of all three cell lines to invade a basement membrane matrix in a chemoinvasion assay. Finally, 8-Cl-cAMP-induced inhibition of GEO tumor growth in nude mice was accompanied by a significant suppression of transforming growth factor alpha, amphiregulin, CRIPTO, basic fibroblast growth factor, and vascular endothelial growth factor production by the tumor cells, and of neoangiogenesis, as detected by factor VIII staining of host blood cells. These results demonstrate that 8-Cl-cAMP is a novel anticancer drug that inhibits the production of various autocrine and paracrine tumor growth factors that are important in sustaining autonomous local growth and facilitate invasion and metastasis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Defective integrin alpha 6 beta 4 expression in the skin of patients with junctional epidermolysis bullosa and pyloric atresia.

Junctional epidermolysis bullosa (JEB) is a heterogeneous group of rare inherited skin disorders in which defects in cell adhesion components cause incomplete formation of hemidesmosomes. We have immunohistochemically examined the skin from ten JEB patients (JEB gravis, n = 4; JEB mitis, n = 3; JEB plus pyloric atresia [JEB/PA], n = 3) using monoclonal antibodies specific for the integrin adhesion receptors alpha 3 beta 1 and alpha 6 beta 4, and for the alpha 3, beta 3, and gamma 2 subunits of the basement membrane ligand, laminin 5. Consistent with our previous reports, only the JEB gravis patients without associated pyloric atresia expressed reduced or absent epitopes for laminin-5 subunits in their epidermal basement membrane. In contrast, all three JEB/PA cases showed abnormalities in integrin alpha 6 beta 4, but not in laminin 5, expression in their basal epidermal cells. Integrin beta 4 subunit was undetectable in the biopsied epidermis of these JEB/PA individuals using five different monoclonal antibodies that recognize both intra- and extracellular epitopes. The absence of the beta 4 subunit in the epidermis of JEB/PA specimens was confirmed by Western blot analysis of tissue extracts. Epidermal expression of the integrin alpha 6 subunit was variable in the JEB/PA patients. Abnormal integrin alpha 6 beta 4 expression may define the subset of JEB cases with pyloric atresia. These results strongly implicate a functional role for alpha 6 beta 4 in the formation of complete hemidesmosomes and in stable adhesion of basal keratinocytes to the basement membrane in vivo.

Adult↗
PubMed1996

Amicrobial pustular dermatosis of cutaneous folds associated with autoimmune disorders: a new entity?

BACKGROUND: An unclassified amicrobial pustular dermatosis particularly affecting the main cutaneous folds, external auditory canals and scalp and coexisting with systemic lupus erythematosus has been recently described. OBJECTIVE: We studied 3 young females bearing such cutaneous manifestations in association with subacute cutaneous lupus erythematosus, celiac disease and various serum autoantibodies, respectively, in order to further characterize this possibly new entity. METHODS: Various routine and immunological laboratory tests, histopathologic and direct immunofluorescence examinations and in vitro studies of neutrophil function were performed in each patient. RESULTS: We reported our findings and compared our cases with the few others appearing in the literature. We documented an impaired neutrophil chemotaxis in 2 subjects, but neutrophil dysfunction does not seem to be one of the verifying criteria. CONCLUSIONS: All of these cases may represent a distinctive form in the clinicopathological spectrum of neutrophilic dermatoses (ND) because of the typical distribution and the close link with different autoimmune disorders. Cimetidine in combination with ascorbic acid can be indicated as an effective and safe alternative to the classic medications of ND, although the action of both drugs remains unexplained.

Adult↗
PubMed1996

Skin ultrastructure after calcipotriol treatment: a transmission electron microscopic and freeze-fracture study on psoriatic patients.

Electron microscopic details in psoriatic skin during calcipotriol application are reported. Ten psoriatic patients (PASI score 3-14) were punch-biopsied on typical lesions before treatment and 2, 4 and 8 weeks after it. Two patients dropped out after 1 month because of lack of clinical response. Skin blocks were processed routinely for transmission electron microscopy and freeze-fracture techniques. The first modifications were the disappearance of fine intercellular granular material and the restoration of the granular layer. After 4 weeks desmosomes appeared in greater amounts than at baseline. Horny layer lipid vacuoles and remnants of nuclei as well as multilayering of the basal lamina were only focally observed. Dilatation of dermal capillaries was still seen even after 8 weeks. Freeze-fracture confirmed the data about the desmosomes and revealed a marked decrease of the gap junctions. Calcipotriol basically seems to act similarly to other antipsoriatic agents, though faster. The persistence of microvasculature dilatation could imply the need for long-term therapy.

Adult↗
PubMed1996

Psoriasiform and sclerodermoid dermatitis of the fingers with apparent shortening of the nail plate: a distinct entity?

A Caucasian boy, born to unrelated parents, and with no family history of psoriasis or atopy, developed chronic psoriasiform dermatitis on the palmar surface of the fingers when he was a year old. At the age of 6, the dorsal surface acquired a sclerodermoid appearance and the nail plates appeared to be shortened. The disease was unsuccessfully treated topically with emollients, keratolytic agents and corticosteroids. At the age of 9, when he was hospitalized, finger motility was limited and painful, and movements of the hands were impaired. The feet were normal. All the investigations were within normal limits. Histology of a biopsy revealed parakeratosis, acanthosis with papillomatosis, exocytosis and spongiosis. He was treated with a new oral non-steroidal anti-inflammatory drug, nimesulide (100 mg/day for 20 days, and then 50 mg/day for 20 days), and emollients. Marked improvement, and restoration of finger motility, were achieved after the first month of treatment; the nail plates reappeared because of regression of the eponychium.

Anti-Inflammatory Agents, Non-Steroidal↗