Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus.

The pathogenesis of uraemic pruritus is unclear, although there is some evidence that an increased number of skin-infiltrating mast cells may play a role. Ultraviolet B reduces itchy sensation of uraemic patients by leading to depletion of cutaneous mast cells. This study presents data that both broad-band and narrow-band ultraviolet B irradiation are able to induce apoptosis in transformed mast cells (murine mastocytoma cell line P815) in a dose-dependent manner at a time point of 24 hours. The positive apoptotic rates were as follows: sham-exposed cells (controls) -- 13.3% +/- 0.6%; with broad-band ultraviolet B irradiation -24.5% +/- 1.1% with 10mJ/cm(2), 57.9% +/- 4.6% with 20mJ/cm(2) and 70.9% +/- 4.5% with 30mJ/cm(2); with narrow-band ultraviolet B irradiation -- 29.6% +/- 2.3% with 100mJ/cm(2), 57.3% +/- 4.1% with 200mJ/cm(2) and 81.5% +/- 1.9% with 300mJ/cm(2). The difference between the number of apoptotic cells in all groups of ultraviolet B-irradiated cells and sham-exposed cells was highly significant (P<0.001). Based on these findings, it is hypothesized that ultraviolet B induced mast cell apoptosis could be an important factor in phototherapy for the diseases dependent on increased number of cutaneous mast cells, including uraemic pruritus.

Ultraviolet A1 (340-400 nm) phototherapy for scleroderma in systemic sclerosis.

BACKGROUND: The presence of an inflammatory infiltrate consisting of helper T cells and a dysregulated matrix metabolism leading to excessive deposition of collagen are two pathogenetic factors responsible for the developments of fibrosis and sclerosis in patients with systemic sclerosis. In previous studies, ultraviolet A1 (UVA1) radiation phototherapy was shown to deplete skin-infiltrating T cells through the induction of T-cell apoptosis and to up-regulate the expression of matrixmetalloproteinase-1 (collagenase-1) in dermal fibroblasts. OBJECTIVE: Our purpose was to determine whether UVA1 phototherapy is effective for systemic sclerosis. METHODS: Lesional skin on the forearms of patients with systemic sclerosis (diffuse type, n =3; limited type, n =1) was exposed to medium-dose UVA1 radiation (60 J/cm(2)) daily. RESULTS: In all patients studied, UVA1 phototherapy-treated skin lesions were markedly softened after 9 to 29 exposures. Clinical improvement was associated with an increase in (1) joint passive range of motion values (P <.05), (2) skin temperature (thermography, P <.05), and (3) cutaneous elasticity (cutaneous elastometry, P <.05). Histologic evaluation of skin specimens obtained before and after UVA1 phototherapy revealed loosening of collagen bundles and the appearance of small collagen fibers. CONCLUSION: These studies indicate that UVA1 phototherapy is effective for patients with systemic sclerosis.

Acute health problems among the people engaged in the cleanup of the Nakhodka oil spill.

To determine if the Nakhodka oil spill and subsequent cleanup efforts had any health effects on the residents along the oil-contaminated coast, we investigated the health status of Anto residents who resided nearest to the coast where the bow ran aground. Two hundred eighty-two men and women involved in the cleanup activities between January 7 and January 20 were interviewed and examined by public health nurses to determine whether they suffered physical symptoms after exposure to the oil spill. Urine examinations for hydrocarbon toxicological markers were performed on 97 residents. The average number of days worked on cleanup activities was 4.7 days for men and 4.3 for women. Seventeen percent of the subjects had worked on cleanup activities for more than 10 days. Protective equipment was used against direct exposure to oil during the cleanup jobs and consisted of gloves used by almost 100% of the subjects and masks used by 87.1% of women and by only 35.4% of men. Glasses were worn by less than 30% of the subjects. Many symptoms emerged after the beginning of cleanup activities. The principal symptoms included low back pain and leg pain, headache, and symptoms of eyes and throat. Among the subjects undergoing urine tests, only three people showed a higher level of hippuric acid, although they returned to normal in the second examination. Accordingly, the exposure to the oil and the subsequent cleanup efforts were suggested to inflict acute health problems on local residents.

Mechanisms of ultraviolet (UV) B and UVA phototherapy.

Ultraviolet (UV) radiation has been used for decades with great success and at a constantly increasing rate in the management of skin diseases, becoming an essential part of modern dermatologic therapy (Krutmann et al, 1999). For phototherapy, irradiation devices emitting either predominantly middlewave UV (UVB, 290-315 nm) or longwave UV (UVA, 315-400 nm) radiation are employed. In former years, patients were treated with broad-band UVB, broad-band UVA, or combination regimens. Broad-band UV phototherapy, however, is being replaced more frequently by the use of irradiation devices that allow treatment of patients' skin with selected emission spectra. Two such modalities which have their origin in European Photodermatology are 311 nm UVB phototherapy (which uses long-wave UVB radiation above 300 nm rather than broadband UVB) and high-dose UVA1 therapy (which selective employs long-wave UVA radiation above 340 nm). In Europe, 311 nm UVB phototherapy has almost replaced classical broad-band UVB phototherapy and has significantly improved therapeutic efficacy and safety of UVB phototherapy (van Welden et al, 1988; Krutmann et al, 1999). The constantly increasing use of UVA-1 phototherapy has not only improved UVA phototherapy for established indications such as atopic dermatitis (Krutmann et al, 1992a, 1998; Krutmann, 1996), but has also provided dermatologists with the opportunity to successfully treat previously untractable skin diseases, e.g., connective tissue diseases (Stege et al, 1997; Krutmann, 1997). These clinical developments have stimulated studies about the mechanisms by which UVB and UVA phototherapy work. The knowledge obtained from this work is an indispensable prerequisite to make treatment decisions on a rationale rather than an empirical basis. Modern dermatologic phototherapy has started to profit from this knowledge, and it is very likely that this development will continue and provide dermatologists with improved phototherapeutic modalities and regimens for established and new indications. This review aims to provide an overview about current concepts of the mode of action of dermatologic phototherapy. Special emphasis will be given on studies that have identified previously unrecognized immunosuppressive/anti-inflammatory principles of UV phototherapy.

Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.

BACKGROUND: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well. OBJECTIVE: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL). METHODS: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically. RESULTS: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed. CONCLUSION: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Evidence that singlet oxygen-induced human T helper cell apoptosis is the basic mechanism of ultraviolet-A radiation phototherapy.

Ultraviolet A (UVA) irradiation is effectively used to treat patients with atopic dermatitis and other T cell mediated, inflammatory skin diseases. In the present study, successful phototherapy of atopic dermatitis was found to result from UVA radiation-induced apoptosis in skin-infiltrating T helper cells, leading to T cell depletion from eczematous skin. In vitro, UVA radiation-induced human T helper cell apoptosis was mediated through the FAS/FAS-ligand system, which was activated in irradiated T cells as a consequence of singlet oxygen generation. These studies demonstrate that singlet oxygen is a potent trigger for the induction of human T cell apoptosis. They also identify singlet oxygen generation as a fundamental mechanism of action operative in phototherapy.

History of vitamin D treatment of renal osteodystrophy.

Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.

Successful treatment of systemic sclerosis with topical PUVA.

Treatment of a 43-year-old woman with systemic sclerosis with 8-methoxypsoralen and ultraviolet. A radiation (PUVA) resulted in the significant clinical and histological improvement of skin lesions without side effects.

Effects of dietary phosphorus restriction on secondary hyperparathyroidism in hemodialysis patients during intermittent oral high-dose 1,25(OH)2D3 treatment.

Phosphorus (P) retention plays an important role in the pathogenesis of secondary hyperparathyroidism (2nd HPT) in chronic renal failure. In recent years, periodic intravenous or intermittent oral administration of high doses of 1,25(OH)2D3 has been reported to improve severe 2nd HPT in hemodialysis patients. The present study was performed to determine the effects of dietary P restriction on 2nd HPT in hemodialysis patients treated with intermittent oral high-dose 1,25(OH)2D3. A high dose of 1,25(OH)2D3 was administered orally twice a week at the end of hemodialysis in 20 hemodialysis patients with 2nd HPT. Dietary P content was estimated from records of the patients' food intake, made twice during the treatment period. Based on this information, dietitians developed appropriate meal plans and instructed the patients. After 8 weeks of the treatment, serum c-parathyroid hormone (c-PTH) and alkaline phosphatase (ALP) levels decreased significantly, from 18.8 +/- 1.9 ng/ml and 347.1 +/- 30.7 U/liter to 9.4 +/- 1.2 ng/ml and 268.3 +/- 19.6 U/liter, respectively. Serum P levels increased gradually during the first 4 weeks of the treatment. Dietary P intake was reduced significantly, from 908 +/- 49 mg/day to 734 +/- 39 mg/day, after the nutritional instructions. As a result of the dietary P restrictions, serum P levels were significantly decreased in the 8th week as compared with those in the 4th week. Serum Ca levels remained unchanged throughout the observation period. There was a significant relationship between the mean values for serum P levels during the study and the percent suppression of serum c-PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intermittent oral 1,25(OH)2D3 therapy on bone Gla protein in dialysis patients.

Serum Bone Gla Protein (BGP) levels were measured by both immunoradiometric assay (IRMA) and radioimmunoassay (RIA) to investigate the effect of intermittent 1,25(OH)2D3 administration to dialysis patients who could not tolerate an increase in an active vitamin D3 dose and/or calcium to control secondary hyperparathyroidism due to hypercalcemia. The administration of active vitamin D3 gradually increased the serum BGP to more than 3 times the original level by the 8th week. At the 12th week after starting the active vitamin D3 therapy, mean BGP was about twice the original level, which was about half the maximum level at the 8th week. The BGP (IRMA)/BGP (RIA) ratio was increased significantly at 4th and 8th weeks compared to the original level. During this period, serum calcium, phosphorous, or intact molecule PTH (I-PTH) levels showed insignificant changes, with a slight reduction in the mid molecule PTH (m-PTH) level, and a significant reduction in ALP. Serum BUN and creatinine levels were not changed significantly. These data suggest that BGP was increased through direct stimulation of osteoblasts by the active vitamin D3, and the increase was not due to deterioration of secondary hyperparathyroidism. The reduction of the increase in the BGP level at the 12th week with insignificant biochemical changes suggest that activation of osteoblasts by vitamin D3 may be transient. In conclusion, intermittent active vitamin D3 increases serum BGP, without deterioration of major biochemical changes even in patients with moderate to severe secondary hyperparathyroidism, although the increase may be transient. These facts suggest that the serum BGP of hemodialysis patients is controlled at least in part by active vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of a case of mycosis fungoides and one of parapsoriasis en plaque with topical PUVA using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin.

A case of plaque stage mycosis fungoides and one of parapsoriasis en plaque were treated with topical PUVA therapy using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin (TMA). Both patients showed complete clearance of eruptions within 16 treatments. The therapeutic effectiveness of TMA was confirmed by the fact that those eruptions exposed to UVA alone, without TMA application, showed slower and less significant improvement. Histologically, dermal infiltrates of mycosis cells and associated epidermotrophism disappeared almost completely in response to TMA PUVA. No side effects or changes in values in laboratory examinations were observed during treatment.

Treatment of PUVA- and retinoid-PUVA-resistant severe psoriasis with systemic cyclosporin A.

Twenty patients with severe psoriasis were treated with the oral administration of 5 mg/kg/day of cyclosporin A (CyA) for 12 weeks. These patients had either failed to respond to or had become unresponsive to conventional treatments including PUVA, UVB, or combinations of etretinate and PUVA or UVB. Complete clearance and marked improvement were observed in 12 (60%) and 4 patients (20%), respectively. The average score of the Psoriasis Area and Severity Index (PASI) was 26.2 before treatment, decreasing to 18.3 in 2 weeks, 8.2 in 6 weeks, and 5.1 in 12 weeks of CyA treatment. There was a tendency for patients with lower blood levels of CyA to show smaller decreases in their PASI scores. In four patients who received skin biopsies, histological improvement was noted within 10 days of treatment; epidermal thickness had decreased by 32%, intraepidermal mitoses by 66%, and parakeratosis had disappeared almost completely. No clinical side effects or alterations in laboratory values were observed that required cessation of CyA. Exacerbations of psoriasis occurred in 11 of 16 patients within 6 weeks after stopping treatment. These results suggest that CyA could be the first choice of treatment for resistant severe psoriasis.

Abnormal fatty acid composition of plasma lipids in patients with protein-losing enteropathy.

This study was performed to clarify how disturbance of lipid metabolism occurred in patients with protein-losing enteropathy (PLE) as compared with that of control individuals and patients with malabsorption syndrome. Analysis of plasma lipids at fasting state showed a decreased proportion of essential fatty acid, especially linoleic and arachidonic acid fractions in patients with malabsorption syndrome as well as in patients with PLE group A, which was due to proven disorders of intestinal lymphatics. An increase in percentage of oleic acid fraction and a percentage increase in plasma triglyceride levels after an oral administration of olive oil was depressed in patients with malabsorption syndrome and PLE group A when compared with that of normal subjects. Patients with PLE group B, which was not due to major lymphatic disorders, were similar to normal in these parameters. These abnormalities were found to be marked when remarkable abnormalities of lymphatics were accompanied.

Chromatographic fractionation and characterization of the active platelet aggregation inhibitory factor from bromelain.

Isolation and characterization of the platelet aggregation inhibitory factor of bromelain have been presented in this study. Commercial bromelain consists of 3 major components as demonstrated by discontinuous sodium chloride gradient chromatography through carbixymethyl-sephadex column. Fraction I constituted approximately 19% of the total fraction. This fraction had no proteolytic activity or platelet aggregation inhibiting activity, but showed peroxidatic activity. Fraction II and III, which constituted the remainder of the fraction eluted with 135 mM and 800 mM NaCl concentrations, respectively, showed both proteolytic and inhibition of platelet aggregation, but no peroxidatic activity. Immunoelectrophoresis and polyacrylamide electrophoresis showed fraction I with beta-mobility while fraction II and III demonstrated gamma-mobility. It is suggested that the proteolytic activity is associated with the inhibition of platelet aggregation, since oxidation of fractions II and III with sodium tetrathionate abolished both activities. The mechanism of inhibition of platelet aggregation by bromelain is presently unknown but may involve its influence on the prostaglandin synthetic pathway of platelets.