Hypertrichosis
Gingival Hyperplasia
Impact of cyclosporin A pharmacokinetics on the presence of side effects in pediatric renal transplantation. (1/51)
Cyclosporin A (CsA) is a potent immunosuppressant that has many side effects, including hypertrichosis, gingival hyperplasia, and tremor. To evaluate whether there is a relationship between the CsA-pharmacokinetics (PK) and these side effects, their presence and intensity were observed in 46 renal transplanted children/adolescents during two regular visits, and the occurrence of the side effects was correlated with CsA-PK. CsA doses had been unchanged for at least 6 mo. CsA blood concentrations were measured at time 0, and 1, 2, and 4 h after the CsA morning dose. An abbreviated area under the curve (AUC) was calculated using C0, C2, and C4. Hypertrichosis positively correlated with C2, C4, Cmax, and AUC. An AUC > or = 4158 ng/ml per h was the best predictor for the presence of hypertrichosis. Tremor was also positively correlated with C2, Cmax, and AUC. A Cmax > or = 878 ng/ml was the best predictor for the appearance of tremor. These values of Cmax and AUC are within the therapeutic range of CsA as demonstrated by the studies of calcineurin inhibition by CsA. Gingival hyperplasia was not associated with any of the CsA-PK studied parameters. However, it was associated with the concomitant use of nifedipine. These data show that there is a correlation between the CsA side effects and its pharmacokinetics and that it is possible to decrease the incidence and intensity of such side effects by monitoring the CsA-PK parameters, providing they are under or at the proposed cutoff levels. Nifedipine should also be avoided to reduce the presence of gingival hyperplasia. (+info)Treatment with cyclosporin switching to hydroxychloroquine in patients with rheumatoid arthritis. (2/51)
OBJECTIVE: To investigate the therapeutic benefit of cyclosporin A (CSA) switching to hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). METHODS: Thirty four patients with RA who displayed residual inflammation and disability despite partial responses to prior maximal tolerated doses of methotrexate, were included. All were treated with a staged approach using CSA for 24 weeks to induce clinical improvement, followed by HCQ for 16 weeks to maintain the improvement. Seven ACR core set measures were evaluated every four to eight weeks. RESULTS: During a 40 week open trial, 27/34 patients completed the study. CSA treatment significantly reduced the tender joints score, swollen joints score, visual analogue pain scale, patient's or doctor's global assessment, patient's self assessed disability, and C reactive protein. Compared with the time of entry into the trial, patients who switched from CSA to HCQ still possessed significantly lower levels of most variables, determined at 28, 32, and 40 weeks. According to the ACR 20% improvement definition, 15/27 (56%) patients had improved at 24 weeks after CSA treatment, and 14/27 (52%) remained improved at 16 weeks after the change to HCQ. Frequent side effects, such as hypertrichosis, gastrointestinal trouble, and hypertension, were noted during CSA treatment, but most of these disappeared after switching to HCQ. The mean levels of blood pressure and serum creatinine were significantly increased during CSA treatment, but returned to normal after changing to HCQ. CONCLUSIONS: The data suggest that CSA switching to HCQ treatment may be an effective strategy for patients with RA partially responding to methotrexate, particularly those with toxicity due to CSA. (+info)Minoxidil-induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil. (3/51)
The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in dermal papilla cells might play a role in the production of adenosine. (+info)Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris. (4/51)
Cell adhesion and communication are interdependent aspects of cell behavior that are critical for morphogenesis and tissue architecture. In the skin, epidermal adhesion is mediated in part by specialized cell-cell junctions known as desmosomes, which are characterized by the presence of desmosomal cadherins, known as desmogleins and desmocollins. We identified a cadherin family member, desmoglein 4, which is expressed in the suprabasal epidermis and hair follicle. The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Characterization of the phenotype of naturally occurring mutant mice revealed disruption of desmosomal adhesion and perturbations in keratinocyte behavior. We provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation. (+info)Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes. (5/51)
One of the most common side effects of treatment with cyclosporin A (CsA) is hypertrichosis. This study shows that calcineurin activity is associated with hair keratinocyte differentiation in vivo, affecting nuclear factor of activated T cells (NFAT1) activity in these cells. Treatment of nude or C57BL/6 depilated normal mice with CsA inhibited the expression of keratinocyte terminal differentiation markers associated with catagen, along with the inhibition of calcineurin and NFAT1 nuclear translocation. This was associated with induction of hair growth in nude mice and retardation of spontaneous catagen induction in depilated normal mice. Furthermore, calcineurin inhibition blocked the expression of p21(waf/cip1) and p27(kip1), which are usually induced with differentiation. This was also associated with an increase in interleukin-1alpha expression (nude mice), a decrease in transforming growth factor-beta (nude and normal mice), and no change in keratinocyte growth factor expression in the skin. Retardation of catagen in CsA-treated mice was accompanied by significant alterations in apoptosis-related gene product expression in hair follicle keratinocytes. The ratio of the anti-apoptotic Bcl-2 to proapoptotic Bax expression increased, and expression of p53 and interleukin-1beta converting enzyme activity decreased. These data provide the first evidence that calcineurin is functionally active in follicular keratinocytes and that inhibition of the calcineurin-NFAT1 pathway in these cells in vivo by CsA enhances hair growth. (+info)KORSAKOFF'S SYNDROME ASSOCIATED WITH ADRENAL VIRILISM. (6/51)
Korsakoff's syndrome of obscure etiology was observed in a 34-year-old single woman with an 11-year history of hirsutism and mood swings, and previous hospitalizations for mania three years ago and depression 11 years ago.Recently the virilism had intensified with increased muscularity and coarsening of facial features. The 24-hour urinary 17-ketosteroids ranged between 14.4 mg. and 21.5 mg. and were suppressed by dexamethasone. The 17-hydroxycorticosteroid excretion was normal. These and other findings suggested a diagnosis of adrenal virilism due to adrenocortical hyperplasia. In the absence of other discernible causes it appeared that the adrenal pathology was responsible for the Korsakoff's syndrome. Both conditions responded well to glucocorticoid therapy although low doses were necessary to avoid mania.It is speculated that the encephalopathy was due to an associated adrenal insufficiency. Although hypoadrenalism is accepted as a complication of only the infant form of adrenal virilism, it is noteworthy that this patient had pathological pigmentation of her skin. (+info)THE DE LANGE SYNDROME: REPORT OF THREE CASES. (7/51)
Three cases of de Lange's syndrome are described. This condition is characterized by generally severe mental retardation, reduced stature, mild microcephaly, hypertrichosis, various anomalies of hands and feet, and a peculiar facies. The most outstanding features of the latter are the low forehead, profuse, generally confluent eyebrows, abundant long eyelashes, eyes that frequently slant downwards and outwards in antimongoloid fashion, pug nose with prominent anteverted nostrils, increased distance between nose and vermilion border of upper lip, slight reduction in size of chin, and often abnormally low-placed ears. The etiology of de Lange's syndrome is at present unknown. (+info)Acquired eyelash trichomegaly and generalized hypertrichosis associated with breast anomaly. (8/51)
Acquired eyelash trichomegaly is a rare condition. We present a 23-year-old woman with acquired trichomegaly and generalized hypertrichosis from childhood. The patient also exhibited bilateral nipple retraction and unilateral left-sided accessory nipple. According to our knowledge the association between trichomegaly, hypertrichosis, and breast anomaly has not been reported. (+info)Hypertrichosis is a medical term that refers to an abnormal growth or overabundance of hair in areas where hair is not typically found or excessively thick. It can affect both men and women, and it can be present at birth (congenital) or develop later in life (acquired). The cause of congenital hypertrichosis is usually genetic, while acquired hypertrichosis can be caused by various factors such as medications, hormonal imbalances, metabolic disorders, or cancer.
Hypertrichosis should not be confused with hirsutism, which is a condition that causes excessive hair growth in women in areas where hair is typically found in men, such as the face, chest, and back. Hirsutism is usually caused by hormonal imbalances, while hypertrichosis can occur anywhere on the body.
Hypertrichosis can be localized, affecting only specific areas of the body, or generalized, affecting large portions of the body. Treatment for hypertrichosis depends on the underlying cause and may include medications to slow hair growth, laser therapy, or hair removal methods such as waxing, shaving, or plucking.
Gingival hyperplasia is a condition characterized by an abnormal growth or enlargement of the gingiva (gum tissue). This condition can be caused by various factors, including bacterial infection, certain medications (such as phenytoin, cyclosporine, and nifedipine), systemic diseases (such as leukemia, vitamin C deficiency, and Crohn's disease), and genetic disorders.
The enlarged gum tissue can be uncomfortable, irritated, and prone to bleeding, especially during brushing or flossing. It may also make it difficult to maintain good oral hygiene, which can increase the risk of dental caries and periodontal disease. Treatment for gingival hyperplasia typically involves improving oral hygiene, controlling any underlying causes, and in some cases, surgical removal of the excess tissue.
Hair removal is the deliberate elimination or reduction of body hair. This can be achieved through various methods, both temporary and permanent. Some common temporary methods include shaving, waxing, tweezing, and depilatory creams. Permanent methods may involve laser hair removal or electrolysis, which target the hair follicle to prevent future growth. It's important to note that some methods can have side effects or risks, so it's recommended to consult with a healthcare professional or dermatologist before starting any new hair removal regimen.
Nucleoside transport proteins (NTTs) are membrane-bound proteins responsible for the facilitated diffusion of nucleosides and related deoxynucleosides across the cell membrane. These proteins play a crucial role in the uptake of nucleosides, which serve as precursors for DNA and RNA synthesis, as well as for the salvage of nucleotides in the cell.
There are two main types of NTTs: concentrative (or sodium-dependent) nucleoside transporters (CNTs) and equilibrative (or sodium-independent) nucleoside transporters (ENTs). CNTs mainly facilitate the uptake of nucleosides against a concentration gradient, using the energy derived from the sodium ion gradient. In contrast, ENTs mediate bidirectional transport, allowing for the equalization of intracellular and extracellular nucleoside concentrations.
Nucleoside transport proteins have been identified in various organisms, including humans, and are involved in numerous physiological processes, such as cell proliferation, differentiation, and survival. Dysregulation of NTTs has been implicated in several pathological conditions, including cancer and viral infections, making them potential targets for therapeutic intervention.