Active hair growth (anagen) is associated with angiogenesis. (73/1928)

After the completion of skin development, angiogenesis, i.e., the growth of new capillaries from pre-existing blood vessels, is held to occur in the skin only under pathologic conditions. It has long been noted, however, that hair follicle cycling is associated with prominent changes in skin perfusion, that the epithelial hair bulbs of anagen follicles display angiogenic properties, and that the follicular dermal papilla can produce angiogenic factors. Despite these suggestive observations, no formal proof is as yet available for the concept that angiogenesis is a physiologic event that occurs all over the mature mammalian integument whenever hair follicles switch from resting (telogen) to active growth (anagen). This study uses quantitative histomorphometry and double-immunohistologic detection techniques for the demarcation of proliferating endothelial cells, to show that synchronized hair follicle cycling in adolescent C57BL/6 mice is associated with substantial angiogenesis, and that inhibiting angiogenesis in vivo by the intraperitoneal application of a fumagillin derivative retards experimentally induced anagen development in these mice. Thus, angiogenesis is a physiologic event in normal postnatal murine skin, apparently is dictated by the hair follicle, and appears to be required for normal anagen development. Anagen-associated angiogenesis offers an attractive model for identifying the physiologic controls of cutaneous angiogenesis, and an interesting system for screening the effects of potential antiangiogenic drugs in vivo.  (+info)

Detection of triazolam and its hydroxy metabolites in rat hair by reversed-phase liquid chromatography with electrospray ionization mass spectrometry. (74/1928)

A sensitive method using reversed-phase liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS) for simultaneous determination of triazolam (TZ) and its hydroxy metabolites in hair has been developed. After the addition of deuterium-labeled 1 -hydroxymethyltriazolam (1-HT-d4) as an internal standard, analytes in hair shaft and hair root samples were extracted with a basic medium, CH2Cl2/MeOH/28% NH4OH (20:80:2), at room temperature overnight. The chromatographic separation of the analytes was achieved using a 3-microm micro HPLC column (100 x 2.0-mm i.d.) with a gradient of acetonitrile in water containing 1% acetic acid as the mobile phase at a flow rate of 0.15 mL/min. The mass spectrometer was operated in selected-ion monitoring mode at quasi molecular ions [M+H]+ of TZ and its metabolites. Under the proposed conditions, the ranges of quantitation of TZ, 1-HT, and 4-HT were 0.1-10 ng/0.2 mL. The method has been applied to determine the hair shaft and hair root incorporation of TZ and its metabolites into Dark Agouti rats administered with 3 mg/kg or 6 mg/kg intraperitoneally twice a day for five days. Judging from the retention behavior by the chromatography and the mass spectra of the peaks detected, TZ, 1-HT, and 4-HT were incorporated in the hair shaft and the hair root. The concentration of 4-HT was the highest of all compounds detected. An unknown substance thought to be 1,4-diHT also appeared in both hair shaft and hair root samples. This substance was obtained from in vitro metabolic studies of TZ using rat liver microsome fraction and was accompanied by the other two metabolites, 1-HT and 4-HT. Structural elucidation was performed with online high-performance liquid chromatography-MS after acetylation of the substance with acetic anhydride and pyridine. This is the first report of the detection of the hydroxy metabolites of TZ in hair. The method has been found to be useful as a screening procedure of TZ intake in humans.  (+info)

Detection of hunter heterozygotes by enzymatic analysis of hair roots. (75/1928)

We have developed a procedure for testing iduronate sulfatase, the enzyme deficient in Hunter syndrome, in single hair roots. Beta-Hexosaminidase was used as the reference enzyme. The ratio of iduronate sulfatase to beta--hexosaminidase, expressed in arbitrary units of activity, is near zero for Hunter patients and greater than 0.6 in almost all roots of normal individuals. Hair roots of Hunter heterozygotes show a characteristic continuum of activity ratios, ranging from totally deficient up to and including the normal range. The results are consistent with the origin of hair roots from a small number of progenitor cells which obey the Lyon hypothesis. The proportion of roots with low activity can be used to discriminate between normal and heterozygous individuals.  (+info)

A gene for hypotrichosis simplex of the scalp maps to chromosome 6p21.3. (76/1928)

Hypotrichosis simplex of the scalp (HSS) is an autosomal dominant form of isolated alopecia causing almost complete loss of scalp hair, with onset in childhood. After exclusion of candidate regions previously associated with hair-loss disorders, we performed a genomewide linkage analysis in two Danish families and localized the gene to chromosome 6p21.3. This was confirmed in a Spanish family, with a total LOD score of 11.97 for marker D6S1701 in all families. The combined haplotype data identify a critical interval of 14.9 cM between markers D6S276 and D6S1607. Localization of the locus for HSS to 6p21.3 is a first step toward identification of the gene. The gene will give important insights into the molecular and cellular basis of hair growth on the scalp.  (+info)

Effects of exercise intensity on the sweating response to a sustained static exercise. (77/1928)

To investigate how the sweating response to a sustained handgrip exercise depends on changes in the exercise intensity, the sweating response to exercise was measured in eight healthy male subjects. Each subject lay in the supine position in a climatic chamber (35 degrees C and 50% relative humidity) for approximately 60 min. This exposure caused sudomotor activation by increasing skin temperature without a marked change in internal temperature. After this period, each subject performed isometric handgrip exercise [15, 30, 45, and 60% maximal voluntary contraction (MVC)] for 60 s. Although esophageal and mean skin temperatures did not change with a rise in exercise intensity and were similar at all exercise intensities, the sweating rate (SR) on the forearm increased significantly (P < 0.05) from baseline (0.094 +/- 0.021 mg. cm(-2). min(-1) at 30% MVC, 0.102 +/- 0.022 mg. cm(-2). min(-1) at 45% MVC, 0.059 +/- 0.009 mg. cm(-2). min(-1) at 60% MVC) in parallel with exercise intensity above exercise intensity at 30% MVC (0.121 +/- 0.023 mg. cm(-2). min(-1) at 30% MVC, 0.242 +/- 0.051 mg. cm(-2). min(-1) at 45% MVC, 0.290 +/- 0.056 mg. cm(-2). min(-1) at 60% MVC). Above 45% MVC, SR on the palm increased significantly from baseline (P < 0.05). Although SR on the forearm and palm tended to increase with a rise in exercise intensity, there was a difference in the time courses of SR between sites. SR on the palm showed a plateau after abrupt increase, whereas SR on the forearm increased progressively during exercise. These results suggest that the increase in SR with the increase in sustained handgrip exercise intensity is due to nonthermal factors and that the magnitude of these factors during the exercise may be responsible for the magnitude of SR.  (+info)

Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers. (78/1928)

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.  (+info)

Groundwater arsenic contamination in Bangladesh and West Bengal, India. (79/1928)

Nine districts in West Bengal, India, and 42 districts in Bangladesh have arsenic levels in groundwater above the World Health Organization maximum permissible limit of 50 microg/L. The area and population of the 42 districts in Bangladesh and the 9 districts in West Bengal are 92,106 km(2) and 79.9 million and 38,865 km(2) and 42.7 million, respectively. In our preliminary study, we have identified 985 arsenic-affected villages in 69 police stations/blocks of nine arsenic-affected districts in West Bengal. In Bangladesh, we have identified 492 affected villages in 141 police stations/blocks of 42 affected districts. To date, we have collected 10,991 water samples from 42 arsenic-affected districts in Bangladesh for analysis, 58,166 water samples from nine arsenic-affected districts in West Bengal. Of the water samples that we analyzed, 59 and 34%, respectively, contained arsenic levels above 50 microg/L. Thousands of hair, nail, and urine samples from people living in arsenic-affected villages have been analyzed to date; Bangladesh and West Bengal, 93 and 77% samples, on an average, contained arsenic above the normal/toxic level. We surveyed 27 of 42 districts in Bangladesh for arsenic patients; we identified patients with arsenical skin lesions in 25 districts. In West Bengal, we identified patients with lesions in seven of nine districts. We examined people from the affected villages at random for arsenical dermatologic features (11,180 and 29,035 from Bangladesh and West Bengal, respectively); 24.47 and 15.02% of those examined, respectively, had skin lesions. After 10 years of study in West Bengal and 5 in Bangladesh, we feel that we have seen only the tip of iceberg.  (+info)

Wnt signaling maintains the hair-inducing activity of the dermal papilla. (80/1928)

The formation of the hair follicle and its cyclical growth, quiescence, and regeneration depend on reciprocal signaling between its epidermal and dermal components. The dermal organizing center, the dermal papilla (DP), regulates development of the epidermal follicle and is dependent on signals from the epidermis for its development and maintenance. GFP specifically expressed in DP cells of a transgenic mouse was used to purify this population and study the signals required to maintain it. We demonstrate that specific Wnts, but not Sonic hedgehog (Shh), maintain anagen-phase gene expression in vitro and hair inductive activity in a skin reconstitution assay.  (+info)