Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D01398 (Dermatol)
 262,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that toxic oxygen free radicals can be involved in the pathogenesis of systemic sclerosis (scleroderma) (SSc). Because the cells that contribute to the generation of free radicals are not known, our aim was (i) to evaluate the ability of unmanipulated and phorbol 12-myristate 13-acetate-stimulated monocytes and polymorphonucleate neutrophils of SSc patients to generate superoxide anion (O2*-); and (ii) to investigate whether the O2*- produced by these cells involved the activation of nicotinamide-adenine dinucleotide diphosphate oxidase biochemical pathway. Employing the superoxide dismutase-inhibitable reduction of cytochrome c to evaluate the generation of O2*-, unmanipulated monocytes of SSc patients generated more O2*- than primary Raynaud's phenomenon patients and normal control monocytes (p = 0.0001), and the release was higher in patients with diffuse cutaneous involvement and 5 y or less disease duration (p = 0.02). The involvement of nicotinamide-adenine dinucleotide diphosphate oxidase in the enhanced 02*- production was demonstrated by the finding that the cytosolic components of the enzyme, p47phox and p67phox, were both translocated to the plasma membrane of enriched but otherwise unmanipulated monocytes of SSc patients. The involvement of mitochondrial oxidases was excluded by the lack of inhibition of O2*- production when monocytes were incubated in the presence of rotenone, a mitochondrial oxidase inhibitor. Upon stimulation with phorbol 12-myristate 13-acetate, monocytes of SSc patients produced more O2*- than controls. In SSc patients untreated polymorphonucleate neutrophils generated significantly less O2*- than monocytes (p = 0.0001) and only slightly more than polymorphonucleate neutrophils of primary Raynaud's phenomenon patients and normal controls (p = 0.03). In conclusion, we demonstrate that in patients with scleroderma, unmanipulated and phorbol 12-myristate 13-acetate-stimulated monocytes release in vitro increased amounts of superoxide anion through the activation of nicotinamide-adenine dinucleotide diphosphate oxidase and, thus, contribute to the oxidative stress found in this disease.
J Invest Dermatol 1999 Jan
PMID:Monocytes of patients wiht systemic sclerosis (scleroderma spontaneously release in vitro increased amounts of superoxide anion. 988 68

We have previously reported the reduction of cicatricial pemphigoid orodynia with minocycline. Tetracycline combined with high dose nicotinamide has also been beneficial in a number of cutaneous immunological disorders. We now report a series of eight cases in whom further subjective or clinical improvement accrued in five, after the addition of high dose (2.5 or 3 g) nicotinamide to minocycline; however, one of these then discontinued the nicotinamide because of headache and nausea, another was withdrawn from the study because of progressive upper respiratory tract mucosal involvement, and two were changed from minocycline to tetracycline because they developed minocycline-induced hyperpigmentation.
Clin Exp Dermatol 1998 Nov
PMID:Combination therapy with nicotinamide and tetracyclines for cicatricial pemphigoid: further support for its efficacy. 1023 19

We report a patient with severe dermatitis herpetiformis (DH) who was intolerant of dapsone, sulphapyridine, systemic steroids, and azathioprine. He was treated effectively with a combination of heparin, tetracycline and nicotinamide.
Clin Exp Dermatol 2000 May
PMID:Dermatitis herpetiformis effectively treated with heparin, tetracycline and nicotinamide. 1084 95

Vitamin B-6 is important for skin development and maintenance. We examined vitamin B-6 metabolism in human and mouse skin collected at different phases of the hair cycle; in hamster melanomas; in normal and immortalized human keratinocytes (HaCaT) and several human melanoma cell lines. Pyridoxamine 5'-phosphate content was higher in mouse and hamster than in human skin. Activity of both pyridoxamine 5'-phosphate oxidase and pyridoxal 5'-phosphate hydrolase was significantly increased in rapidly growing melanomas compared to either normal skin or slower growing skin tumors. Reducing the pyridoxine content of the culture medium significantly increased the activity of pyridoxal kinase and pyridoxamine 5'-phosphate oxidase. Pyridoxal 5'-phosphate hydrolase has been proposed as a regulatory enzyme for vitamin B-6, but we found B-6 vitamer content to be significantly correlated only with kinase and oxidase activity and not with pyridoxal 5'-phosphate hydrolase activity. Although pyridoxal 5'-phosphate hydrolase activity is usually attributed to tissue-nonspecific alkaline phosphatase, tissue-nonspecific alkaline phosphatase knockout mice showed preservation of normal histology of the skin and adnexal structures. Furthermore, expression of tissue-nonspecific alkaline phosphatase mRNA was not detected in either HaCaT cells or human skin, both of which exhibited significant pyridoxal 5'-phosphate hydrolase activity. This suggests that an enzyme different from the classical tissue-nonspecific alkaline phosphatase may perform cutaneous pyridoxal 5'-phosphate hydrolase activity.
J Invest Dermatol 2003 Feb
PMID:Cutaneous metabolism of vitamin B-6. 1254 35

Among many important physiological functions played by NADH (the reduced form of beta-nicotinamide adenine dinucleotide) its antioxidative properties are remarkable. Acting directly as an antioxidant, NADH can effectively protect the cell and its membrane from destruction by free radicals. NADH can be stabilized as a suspension in hydrophobic ointments prepared in a way that prevents contact with atmosphere containing oxygen and water. We present the first report of NADH as a treatment for some inflammatory dermatoses. It was found that topical application of 1% NADH diluted in Vaseline ointment can be very effective in the treatment of rosacea and contact dermatitis. Since no adverse effects were observed, therapy with NADH can be viewed as a potential alternative to other established treatments.
Clin Exp Dermatol 2003 Jan
PMID:Topical application of NADH for the treatment of rosacea and contact dermatitis. 1255 33

A 68-year-old Japanese male with a five-year-history of lung carcinoma showed recurrent blisters and erosions on the oral and genital mucosae and the skin. The patient complained of dyspnea due to severe laryngeal stenosis and underwent a tracheostomy. A skin biopsy specimen showed a subepidermal blister and linear deposits of IgG and C3 at the basement membrane zone of the epidermis. Indirect immunofluorescence examination demonstrated circulating IgG anti-basement membrane zone autoantibodies that reacted to epiligrin on immunoblotting. Based on a diagnosis of anti-epiligrin cicatricial pemphigoid, he was treated with prednisolone, minocycline hydrochloride and nicotinamide. Although no new skin lesions appeared, he died of lung carcinoma five months after the tracheostomy. A review of reported cases with anti-epiligrin cicatricial pemphigoid in Japan disclosed that 5 of 16 cases (31.2%) were complicated by internal malignancies.
J Dermatol 2004 Jan
PMID:A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: review of Japanese cases and evaluation of risk for internal malignancy. 1473 97

Adenosine diphosphate ribose (ADPR) pyrophosphohydrolase (ADPR-PPase), which catalyzes the hydrolysis of ADPR to yield adenosine monophosphate (AMP) and ribose-5'-phosphate, was assayed in human penile foreskin. Since ADPR is formed from nicotinamide adenine dinucleotide (NAD) by NAD glycohydrolase (NADase), NADase was also assayed in human skin. The skin tissue obtained by circumcision was separated into three layers; epidermis of the outer prepuce, epidermis of the inner prepuce, and dermis. ADPR-PPase was found to be present in all of the three layers with nearly equal activity. NADase was also present in the epidermis of both the outer and inner prepuce, being about two times higher in the latter, but no activity was found in the dermis. When expressed in units of the same specific activity; i.e., micromoles product formed per hour per mg protein, the ADPR-PPase of human skin had two to five times greater activity than did NADase. The ADPR-PPase of human skin was activated by Mg(+2), but inhibited by AMP and ATP. These results suggest that the breakdown of NAD occurs in human skin via ADPR to AMP and ribose-5'-phosphate by sequential action of NADase and ADPR-PPase.
J Dermatol 1980 Feb
PMID:Adenosine diphosphate ribose pyrophosphohydrolase in human skin. 1546 70

We present a 69-year-old woman with refractory bullous pemphigoid successfully treated with pulsed intravenous cyclophosphamide therapy. Because various other early treatments including 4,4'-diaminodiphenylsulphone (DDS), minocycline/nicotinamide, cyclosporin, azathioprine, high-dose oral prednisolone, and methylprednisolone pulse therapy were either ineffective or intolerable, she was treated with double filtration plasmapheresis, but she responded poorly with the rare complication of severe transient thrombopenia. Finally, she gradually recovered with pulsed intravenous cyclophosphamide therapy.
J Dermatol 2004 Aug
PMID:A case of refractory bullous pemphigoid with plasmapheresis-associated thrombopenia: efficacy of pulsed intravenous cyclophosphamide therapy. 1549 38

In 1953, Lever differentiated bullous pemphigoid from autoimmune pemphigus. The natural course of bullous pemphigoid is relatively benign, with a disease-related mortality rate of 24% compared with around 70% in pemphigus. In spite of the introduction of systemic corticosteroids, the mortality rates in bullous pemphigoid have generally not improved and vary between 0% and 40%. Higher doses of systemic corticosteroids seem to be associated with higher mortality rates, which led to the addition of corticosteroid-sparing agents to the treatment of bullous pemphigoid. However, many of these modalities are also accompanied by severe adverse effects and have not led to a significant decrease in the mortality rate. In recent years, there has been a move toward less toxic treatment options for a disease that is usually self-limited. A systematic review of the literature found that treatment with lower doses of systemic corticosteroids and potent topical corticosteroids is effective and accompanied by less serious adverse effects, including death. No benefit of the addition of plasmapheresis or azathioprine to systemic corticosteroids has been shown. The treatment of bullous pemphigoid with tetracyclines and niacinamide (nicotinamide) is effective and accompanied by less serious adverse effects. However, more randomized controlled trials are needed to confirm these results and to determine the best treatment for bullous pemphigoid.
Am J Clin Dermatol 2004
PMID:Management of bullous pemphigoid: recommendations for immunomodulatory treatments. 1555 33

The treatment of cicatricial pemphigoid, also called mucous membrane pemphigoid (MMP), poses a great challenge, because the condition often takes an intransigent course despite all therapeutic efforts. Because of its diverse clinical manifestations, patients with MMP often have to be treated by a variety of specialists, including dermatologists, ophthalmologists, ear, nose, and throat specialists, and dentists. Since there are almost no randomized, controlled, double-blind studies comparing the use of various therapeutic agents in this condition, treatment decisions still rely heavily on individual clinicians' experience. Many different therapeutic regimens have been described in the literature, but only a few seem to hold up as valid alternatives. Systemic corticosteroids are still the agent of first choice, especially as rescue medication, for curtailing acute exacerbations. However, because of their well known long-term adverse effects, corticosteroids must be combined with immunosuppressive and/or anti-inflammatory agents. To determine which drug to choose, it is helpful to categorize patients -- as recommended by the First International Consensus -- in terms of high- and low-risk depending on the site and severity of their disease and on how rapidly it progresses. The recommended treatment for high-risk patients (i.e. patients with ocular, genital, laryngeal, esophageal or nasopharyngeal involvement) is a combination of prednisone and cyclophosphamide, or alternatively azathioprine. Once clinical improvement is evident, the corticosteroids should be slowly tapered. Dapsone is another alternative that may be used in high-risk patients, but patients who do not show any short-term improvement on this regimen should be switched to cyclophosphamide. Intravenous immunoglobulins are another effective, but expensive, treatment option in high-risk patients. Low-risk patients may well be managed with topical therapy alone, such as corticosteroids or cyclosporine. Other systemic options include dapsone, tetracycline, and nicotinamide as well as azathioprine in combination with low doses of corticosteroids. Various other systemic and topical agents, and recently biologics such as etanercept, have been reported to be effective in the treatment of MMP. However, most of the reported cases consisted of only small patient numbers and the true benefit of such agents in the condition is therefore not yet clear.
Am J Clin Dermatol 2005
PMID:Cicatricial pemphigoid (mucous membrane pemphigoid): current and emerging therapeutic approaches. 1579 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>