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Biomedical subjects

P Redondo

Publications and source records attributed to P Redondo.

At least 37 records · Page 2Linked to original sources
PubMed2000

N-acetylcysteine downregulates vascular endothelial growth factor production by human keratinocytes in vitro.

The present study was designed to evaluate the action of various antioxidants including N-acetylcysteine (NAC) and the flavonoids resveratrol and quercetin on the production of VEGF by human keratinocytes (HKC). NAC, resveratrol, and quercetin dose-dependently suppressed the incorporation of 3H-thymidine into HKC. Values of median inhibitory concentration for NAC, resveratrol, and quercetin were 10 mM, 55 microM, and 15 microM, respectively (P < 0.01). RT-PCR demonstrated VEGF 121 and VEGF 206 expression in all HKC samples. HKC showed baseline expression and a progressive gradual time-dependent increase in VEGF secretion (510+/-75 pg/ml at 24 h), and EGF (2.5-100 ng/ml) enhanced the secretion of VEGF in a dose-dependent fashion. HKC were incubated with NAC (2.5-20 mM) for 2 h prior to the addition of EGF (5 ng/ml) or PMA (10 ng/ml), and a significant decrease (P < 0.01) was found after 24 h of incubation with 2.5 mM NAC. However, neither resveratrol nor quercetin reduced the synthesis of this cytokine. In summary we conclude that NAC and the flavonoid antioxidants resveratrol and quercetin inhibit HKC proliferation regardless of the stage of differentiation and that NAC significantly inhibits VEGF secretion in basal and EGF- or PMA-treated HKC.

Acetylcysteine↗
PubMed2000

Cidofovir inhibits growth of B16 melanoma cells in vivo.

BACKGROUND: Cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine] is a commercially available nucleotide analogue that has antiviral activity against a broad range of DNA viruses and is effective against human cytomegalovirus infection. OBJECTIVES: We aimed to study the effect of cidofovir on growth of the highly aggressive melanoma tumour arising from mouse melanoma B16 cells grafted subcutaneously in C57B16/J mice. METHODS: Mice were treated daily with systemic cidofovir at several doses. In treated and control groups, tumour growth was measured using a calliper, and histological studies were performed. RESULTS: In untreated mice, massive invasive melanoma tumours were observed on day 5 after tumour cell grafting. Cidofovir treatment gave a dose-dependent reduction in tumour size. Tumour growth was inhibited by 62% at a dose of 37.5 mg kg(-1) three times weekly, as compared with control mice treated with saline alone. At 67 mg kg(-1) three times weekly, tumour growth was inhibited by 90%. Increasing the cidofovir dose to 50 or 100 mg kg(-1) daily resulted in a gradual increase in the antitumoral effect of the compound. In one experiment, cidofovir was administered at 100 mg kg(-1) five times weekly from the eighth day after the injection of tumour cells, when the tumour already had a volume of approximately 100 mm(3). In the treatment group, on the 14th day the tumour volume was approximately 200 mm(3), while in the control group it had increased to 750 mm(3). CONCLUSIONS: Although the mechanism is unknown, an antitumoral or antiangiogenic effect may be the reason for the activity of cidofovir in this model. In view of our findings, use of cidofovir should be further explored in the treatment of neoplastic diseases.

Animals↗
PubMed2000

Surgical versus interventional procedures in patients with multivessel coronary artery disease.

OBJECTIVE: This study examined the clinical characteristics, risk factors, indications and post-intervention complications of patients with multivessel coronary artery disease (CAD) submitted to either percutaneous transluminal coronary angioplasty (PTCA) and/or stent placement versus isolated coronary artery bypass grafting (CABG). BACKGROUND: Several studies have examined the relative safety and outcome of patients submitted to those interventional procedures compared to CABG. Limited information is available regarding that subject in Puerto Rico. METHODS: We performed a retrospective analysis of the clinical, angiographic, operative, interventional, post-operative and post-interventional data of patients submitted to those procedures in our institution from January 1998 to August 1998. There were 53 patients in the interventional group and 206 patients in the CAGB group. Comparison of quantitative variables by procedure was based on Student t test or Mann-Whitney-Wilcoxon test; categorical variables were compared using Pearson's chi-square or Fisher's exact test. RESULTS: There were no significant differences in age, body surface area, or cardiac risk factors. The most common pre-existing cardiovascular diagnosis was unstable angina. Three-vessel disease was the most common angiographic finding among CABG patients (61.7%). Two-vessel disease without left anterior descending coronary artery obstruction was significantly more common in the PTCA/Stent patients (58.5%). The vast majority (97.6%) of patients in the PTCA/Stent group and 52.4% of the CABG group had two-vessel intervention. A significantly higher frequency of complications occurred in the CABG group. However, the incidence of major complications, in both groups was not statistically different. Atrial arrhythmias were significantly more frequent in the CABG group. CONCLUSION: A larger prospective study should be conducted in order to corroborate these preliminary findings and seek effective solution to any identifiable problem.

Angioplasty, Balloon, Coronary↗
PubMed1999

Topical N-acetylcysteine for lamellar ichthyosis.

The antioxidant N-acetylcysteine has an antiproliferative effect on a culture of human keratinocytes. We report a patient with lamellar ichthyosis satisfactorily treated with topical N-acetylcysteine.

Acetylcysteine↗
PubMed1998

Alpha-MSH regulates interleukin-10 expression by human keratinocytes.

Normal human keratinocytes (HKC) are able to synthesize alpha-MSH. Because the production of alpha-MSH by HKC is induced significantly by ultraviolet B radiation, the involvement of keratinocyte-derived alpha-MSH in UV-induced immunosuppression has been suggested. The induction of the antiinflammatory cytokine IL-10 in monocytes is a major mechanism in the antiinflammatory actions of alpha-MSH. In the present study, HKC were investigated for their ability to produce IL-10 after alpha-MSH stimulation. HKC were obtained from the skin of human female breast sections and either left untreated or treated with 0.01 or 0.1 microg/ml alpha-MSH for different times. Using RT-PCR, HKC were shown to express IL-10 mRNA even under basal conditions, and treatment with alpha-MSH increased expression. Only minimal concentrations of IL-10 protein were detected in supernatants from the alpha-MSH-stimulated cultures. To the best of our knowledge this is the first report of IL-10 expression by cultured HKC after alpha-MSH stimulation. Further studies are needed to determine the biological and therapeutic relevance of these findings.

Female↗
PubMed1998

CD24 expression on human keratinocytes.

CD24 or Nectadrin is a cell surface glycoprotein expressed in pre-B lymphocytes, T lymphocytes, neurons, muscle cells and carcinoma cells. Its function is not completely known, but it has been suggested that it is involved in cell adhesion and signalling. CD24 has recently been identified as the human molecule homologous to the murine heat-stable antigen (HSA). HSA is expressed by murine keratinocytes and delivers costimulatory signals in T-cell activation. Long-term cultures of normal human keratinocytes (HKC) were obtained from skin of human female breast sections and either left untreated or were treated with phorbol-12-myristate-13-acetate (PMA) at 10-100 ng/ml, calcium 0.5-2 mM or IFN-gamma 100-1000 U/ml, for 24-48 h. Using RT-PCR and flow cytometry we showed that HKC express low levels of CD24 even under basal conditions, and the treatment with calcium, PMA or IFN-gamma increased levels of CD24 mRNA and protein. To the best of our knowledge, this is the first report to measure CD24 expression and production by cultured HKC in basal conditions and after stimulation. Further studies are needed to determine biological and therapeutical relevance of these findings.

Antigens, CD↗
PubMed1997

Differential modulation of IL-8 and TNF-alpha expression in human keratinocytes by buflomedil chlorhydrate and pentoxifylline.

Pentoxifylline (PTX) is a methylxanthine derivative used in a wide range of dermatoses. As well as its hemorrheologic activity, PTX has anti-inflammatory properties. Buflomedil chlorhydrate (BC) is another hemorrheological drug with peripheral vasodilatory action, whose clinical uses are similar to those of PTX. Both drugs increase intracellular levels of cAMP, either secondary to phosphodiesterase inhibition (PTX) or adenyl-cyclase stimulation (BC). Long-term cultures of normal human keratinocytes were prepared in a free-serum medium, and stimulated with 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC (100-1000 micrograms/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1 using ELISA and Northern blot or RT-PCR techniques were measured. TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA did not induce IL-1 alpha or IL-1 beta release of keratinocytes. TPA increased RNA expression of the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1. BC diminished TPA-induced TNF-alpha and IL-8 release from keratinocytes; in the case of IL-8 it is possible that this inhibition occur to transcriptional level. Moreover PTX was unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced TPA-induced IL-1 alpha and beta expression. It is possible that BC action is specifically exerted on keratinocytes, because we did not find similar results with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells.

Cells, Cultured↗
PubMed1996

Imipenem therapy of brain abscesses.

The efficacy of imipenem versus standard chemotherapy (both in addition to neurosurgery) in the treatment of brain abscess was compared in a retrospective study. Cure was obtained in 52 of 60 (86.7%) patients in the standard group, and in 15 of 15 (including 5 patients with multiple brain abscesses) in the imipenem group. Cure without neurosurgery was observed in 2 of 60 (3.3%) and 3 of 15 (20%) of the cases, respectively (p = 0.08). Levels of imipenem in blood, cerebrospinal fluid, and brain pus were above the minimum inhibitory concentrations of most of the abscess isolates. Side effects of imipenem were rare and tolerance was excellent. Imipenem monotherapy (3-4 g/day) for five weeks seems a reasonable therapeutic choice for treatment of bacterial brain abscesses.

Adolescent↗
PubMed1996

Photo-induced toxic epidermal necrolysis caused by clobazam.

Toxic epidermal necrolysis (TEN) is a life-threatening disease, the pathogenesis of which remains largely unknown. We describe a 23-year-old woman under treatment with clobazam who developed lesions of TEN in light-exposed areas. Patch and photopatch tests with clobazam were negative. The cellular phenotype and cytokines were studied in blister fluid. The cellular infiltrate was composed mainly of T lymphocytes with a predominant cytotoxic phenotype. There was an increase in the level of tumour necrosis factor (TNF)-alpha in blister fluid compared with the control (a patient with bullous pemphigoid).

Adult↗