Studies of the effects of glucocorticoid (GC) and oxidative stress stimuli in differentiated cultures of human trabecular meshwork (HTM) cells have provided the rationale for our studies of a major new gene termed TIGR (trabecular meshwork inducible GC response). The TIGR clone was isolated by differential library screening using selection criteria based on the induction pattern of a new protein/glycoprotein found in HTM cultures after prolonged but not brief exposure to GCs. This GC induction patter matched the time course and dose response required for intraocular pressure elevation in patients receiving corticosteroids. The very large, progressive induction of TIGR combined with specific structural features of its cDNA suggested that TIGR should be considered a candidate gene for outflow obstruction in glaucoma. Among the properties of TIGR cDNA were a signal sequence for secretion, several structural features for interactions with glycosaminoglycans and other glycoproteins and putative sites for cell surface interactions. In addition, the leucine zippers in the structure were related to TIGR-TIGR oligomerization that was shown to occur with native and recombinant TIGR protein. The verification that TIGR was a major stress response protein in HTM cells following hydrogen peroxide (or phorbol esters) exposure provided a potential link between GC and oxidative mechanisms thought to be involved in glaucoma pathogenesis. Pharmacological evaluation showed that basic fíbroblast growth factory and transforming growth factor β decreased the GC induction of TIGR, and certain nonsteroidal anti-inflammatory drugs protected against both GC- and oxidation-induced stress responses in HTM cells. Our recent studies of TIGR’s genomic structure have shown motifs in the promoter region that suggest a basis by which multiple hormonal/environmental stimuli can regulate TIGR production and by which putative genetic alterations could lead to an overexpression of the protein. Further application of cell biology/biochemistry, molecular biology, genetic and histological approaches will be helpful in understanding the role of TIGR in different glaucoma syndromes.
A total of 238 patients with a clinical diagnosis of localized hyperhidrosis (HH) were treated on 332 anatomic sites (axillae, feet, hands, and groin). The purpose of the study was to evaluate the effectiveness of aluminum chloride hexahydrate (AC), in a salicylic acid gel base (SAGB) containing 4% salicylic acid (SA), for the treatment of localized HH. The SAGB was similar to a keratolytic gel, 1Keralyt® (Westwood Squibb). Because SAGB and anhydrous alcohol (AA), the standard vehicle for AC, have different consistencies, double blinding was not possible. Bromhidrosis (BH) was documented when present, whether of apocrine (axillae and groin) or eccrine (feet) origin. For the sake of uniformity, AC in SAGB was compounded by the same pharmacist. The concentration of AC varied from 10 to 40%, depending on the site to be treated. The improvement of HH was subjectively assessed through a questionnaire as follows: nil = no improvement; poor = <25%; fair = 25–50%; good = 50–75%; and excellent = >75%.
Armpits: 20% AC was used to control axillary HH. When 20% AC failed to control HH, its concentration was gradually increased to 25% and, rarely, to 30%. When irritation occurred, the concentration of AC was decreased to 15 or 10%, and 1% hydrocortisone (HC) was added to the preparation. Patients were instructed to apply the medication initially 2–3 nights per week, gradually decreasing the frequency as required. When possible, only the active focal area of HH was treated.
2As with AC in AA, the medication was applied at bedtime. Patients were instructed to avoid rubbing and the application of the medication on recently shaved skin.
Hands and feet: for these areas, the concentration of AC was 30% initially, but could be increased up to 40% if necessary.
3Application was daily at bedtime, and later at gradually longer intervals. Occlusion was never used.
Topical FK506 has recently been shown to have an anti-inflammatory effect in vivo in humans. In this study its effects in contact dermatitis were studied in the guinea pig model. Topical FK506 suppressed both irritant and allergic patch-test reactions. The most prominent suppressive effect was seen when skin sites were pretreated with FK506. Topical FK506 did not impair the induction of contact allergy as assessed by challenges, although it suppressed local lymph node cell accumulation during contact allergy induction. Topical FK506 may hold promise as a treatment for skin disorders that respond to oral FK506 or cyclosporin A.
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