ABSTRACT
Hair loss is a complex and multi-factorial problem that is associated with significant psychological morbidity in women. Menopausal women represent a significant percentage of those affected, since the menopausal hormonal transition can be a contributing factor. A novel nutraceutical supplement has been specifically formulated with phytoactives to improve hair growth and quality in menopausal women (Nutrafol® Women’s Balance Capsules). The objective of this 6-month, randomized, double-blind, placebo-controlled study was to assess the safety and efficacy of this oral supplement to promote hair growth in perimenopausal, menopausal, and postmenopausal women with self-perceived thinning. Subjects were randomized to the study supplement (n=40) or placebo (n=30). The primary endpoint was a statistically significant increase in the number of terminal and vellus hairs based on phototrichogram analysis. Daily intake of the nutraceutical supplement resulted in progressive and significant increase in terminal and total hair counts on days 90 (P<0.01) and 180 (P<0.01) compared to placebo. The vellus hair counts significantly increased for the active treatment group (P<0.05) by day 180 while significantly decreasing for the placebo group subjects. Hair shedding progressively and significantly decreased for the active group compared to placebo, culminating in a reduction of 32.41% by day 180 (P<0.01). The study supplement was well-tolerated. ClinicalTrials.gov Identifier: NCT04048031 J Drugs Dermatol. 2021;20(1):55-61. doi:10.36849/JDD.5701 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.
Subject(s)
Alopecia/drug therapy , Dietary Supplements/adverse effects , Hair/drug effects , Menopause/physiology , Phytochemicals/administration & dosage , Administration, Oral , Adult , Aged , Alopecia/diagnosis , Alopecia/physiopathology , Dermoscopy/methods , Double-Blind Method , Female , Hair/diagnostic imaging , Hair/growth & development , Humans , Middle Aged , Photography , Phytochemicals/adverse effects , Placebos/administration & dosage , Surveys and Questionnaires , Treatment OutcomeABSTRACT
INTRODUCTION: Androgenetic alopecia is the most common form of hair loss in both sexes. In recent studies, low-level light therapy (LLLT) has been established as an effective treatment for alopecia. The purpose of this study was to evaluate the safety and efficacy of LLLT using a new helmet-type device for the treatment of androgenetic alopecia. METHOD: A randomized, sham device-controlled, double-blind clinical trial was conducted at 2 institutions. Sixty participants diagnosed with androgenetic alopecia aged from 19 to 65 years were recruited. LLLT was performed through a helmet-type device that emitted light with a mean output power of 2.36âmW/cm at a wavelength of 655ânm. Participants were divided into 2 groups, which respectively used the experimental device and a sham device. After tattooing at the central point of the vertex, phototrichograms at that point were obtained at 0, 8, and 16 weeks. The primary endpoint of the study was the difference in the rate of change of hair density between the test group and the control group. RESULTS: Comparing the results at baseline and week 16, the experimental group showed an increase in hair density of 41.90âhairs/cm and an increase in hair thickness of 7.50âµm, whereas the control group showed an increase of 0.72âhairs/cm and a decrease of 15.03âµm, respectively (Pâ<â.001). No adverse events or side effects occurred. CONCLUSION: LLLT showed a significant effect on increasing hair density in patients with androgenetic alopecia. LLLT could be a safe and effective treatment for androgenetic alopecia in both sexes.
Subject(s)
Alopecia/urine , Head Protective Devices/standards , Low-Level Light Therapy/standards , Adult , Aged , Alopecia/physiopathology , Double-Blind Method , Equipment Design/methods , Female , Head Protective Devices/statistics & numerical data , Humans , Low-Level Light Therapy/methods , Low-Level Light Therapy/statistics & numerical data , Male , Middle Aged , Placebos/administration & dosage , Treatment OutcomeABSTRACT
Androgenetic alopecia (AGA) is the most common hair loss disorder in men and women. The characteristic and reproducible balding pattern in AGA negatively affects self-image and the external perceptions of the balding patient. The phenotypical changes are driven by dihydrotestosterone (DHT) and its precursor testosterone. DHT induces follicle miniaturization and hair cycle changes until resulting hairs no longer extrude through the skin surface. AGA is inherited in a polygenetic pattern and is susceptible to epigenetic and environmental factors. Currently, minoxidil, finasteride, and photolaser therapy are the only Food and Drug Administration-approved medical treatments for AGA.
Subject(s)
Alopecia/physiopathology , Alopecia/therapy , Hair Preparations/administration & dosage , Alopecia/etiology , Alopecia/metabolism , Dihydrotestosterone/metabolism , Dutasteride/administration & dosage , Finasteride/administration & dosage , Humans , Low-Level Light Therapy , Minoxidil/administration & dosageABSTRACT
Androgenetic alopecia (AGA) is the most diagnosed hair loss dysfunction. Its physiopathology comprises a genetic predisposition affording an exacerbated response of the hair follicles cells to androgens aggravated by scalp inflammation and extrinsic factors. This paper presents a review of the mechanisms and extrinsic factors involved in the AGA physiopathology as well as its conventional and emerging treatments. The research focused on reports regarding AGA physiopathology and treatments published between January 2001 and July 2019 in medical and related journals. The most used medical treatments for AGA-minoxidil and finasteride-present non satisfactory results in some cases. Currently, the low-level laser therapy is recognized as a safe and effective treatment for AGA. Some minimally invasive techniques-mesotherapy, microneedling, carboxytherapy, and platelet-rich plasma-are also used to stimulate hair growth. Pharmaceutical substances with mechanisms differing from the anti-androgen activity are under current investigation and many of them have botanical origins; however, formulations with higher performance are required, and the hair follicles ability of being a drug and nanoparticle reservoir has been researched. The association of different strategies, that is, substances with synergic mechanisms and the use of advantageous technologies associated with lifestyle changes could improve the treatment outcomes.
Subject(s)
Alopecia/physiopathology , Alopecia/therapy , Androgen Antagonists/administration & dosage , Hair/drug effects , Low-Level Light Therapy/methods , Adult , Alopecia/genetics , Finasteride/administration & dosage , Genetic Predisposition to Disease , Hair/growth & development , Humans , Male , Middle Aged , Minoxidil/administration & dosage , Platelet-Rich Plasma , Prognosis , Risk Assessment , Treatment OutcomeABSTRACT
This study aims to investigate the biological activities related to hair loss of Equisetum debile extracts, including 5α-reductase inhibition, interleukin-6 (IL-6) secretion reduction, and anti-oxidation. E. debile extracts were obtained by maceration in various solvents. Crude extract (CE) was obtained by maceration in 95% ethanol. Chlorophyll-free extract (CF) was the CE which of the chlorophyll has been removed by electrocoagulation. Hexane extract (HE), ethyl acetate extract (EA), and ethanolic extract (ET) were fraction extracts obtained from maceration in hexane, ethyl acetate, and 95% ethanol, respectively. The extracts were investigated for inhibitory activity against 5α-reductase and IL-6 secretion. Total phenolic contents (TPC) were investigated and antioxidant activities were determined by means of 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. The inhibition of lipid peroxidation was determined by the ferric thiocyanate method. The cytotoxicity of the extracts on dermal papilla cells and irritation test by hen's egg test chorioallantoic membrane assay were also investigated. All extracts could inhibit 5α-reductase and decrease IL-6 secretion in lipopolysaccharide-stimulated macrophage. The antioxidant activity of E. debile extracts was directly related to their TPC. ET which contained the highest TPC (68.8 ± 6.7 mg GA/g) showed the highest equivalent concentration (EC1) of 289.1 ± 26.4 mM FeSO4/g, TEAC of 156.6 ± 34.6 mM Trolox/g, and 20.0 ± 6.0% DPPH inhibition. However, EA exhibited the highest inhibition against lipid peroxidation (57.2 ± 0.4%). In addition, EA showed no cytotoxicity on dermal papilla cell line and no irritation on chorioallantoic membrane of hen's eggs. In conclusion, EA was suggested as the most attractive ingredients for functional food and nutraceuticals because of the high inhibitory activity against 5α-reductase, IL-6 secretion, and lipid peroxidation inhibition.
Subject(s)
5-alpha Reductase Inhibitors/pharmacology , Alopecia/prevention & control , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Dietary Supplements , Equisetum/chemistry , Functional Food , Interleukin-6/metabolism , Macrophages/drug effects , Plant Extracts/pharmacology , 5-alpha Reductase Inhibitors/chemistry , 5-alpha Reductase Inhibitors/isolation & purification , 5-alpha Reductase Inhibitors/toxicity , Alopecia/enzymology , Alopecia/physiopathology , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/toxicity , Antioxidants/chemistry , Antioxidants/isolation & purification , Antioxidants/toxicity , Benzothiazoles/chemistry , Biphenyl Compounds/chemistry , Cell Line, Tumor , Chick Embryo , Chlorides/chemistry , Cholestenone 5 alpha-Reductase/metabolism , Chorioallantoic Membrane/drug effects , Chorioallantoic Membrane/pathology , Ferric Compounds/chemistry , Humans , Lipid Peroxidation/drug effects , Macrophages/metabolism , Male , Mice , Phenols/isolation & purification , Phenols/pharmacology , Picrates/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Prostatic Neoplasms/enzymology , RAW 264.7 Cells , Solvents/chemistry , Sulfonic Acids/chemistryABSTRACT
BACKGROUND AND OBJECTIVE: Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. MATERIAL AND METHODS: The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches. The functional significance of Opsin 3 was assessed by silencing its expression in the hair follicle cells followed by a transcriptomic profiling. Proprietary LED-based devices emitting two discrete visible wavelengths were used to access the effects of selected optical parameters on hair growth ex vivo and outer root sheath cells in vitro. RESULTS: The expression of OPN2 (Rhodopsin) and OPN3 (Panopsin, Encephalopsin) was detected in the distinct compartments of skin and anagen hair follicle. Treatment with 3.2 J/cm2 of blue light with 453 nm central wavelength significantly prolonged anagen phase in hair follicles ex vivo that was correlated with sustained proliferation in the light-treated samples. In contrast, hair follicle treatment with 3.2 J/cm2 of 689 nm light (red light) did not significantly affect hair growth ex vivo. Silencing of OPN3 in the hair follicle outer root sheath cells resulted in the altered expression of genes involved in the control of proliferation and apoptosis, and abrogated stimulatory effects of blue light (3.2 J/cm2 ; 453 nm) on proliferation in the outer root sheath cells. CONCLUSIONS: We provide the first evidence that (i) OPN2 and OPN3 are expressed in human hair follicle, and (ii) A 453 nm blue light at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. Lasers Surg. Med. 49:705-718, 2017. © 2017 Wiley Periodicals, Inc.
Subject(s)
Alopecia/radiotherapy , Hair Follicle/metabolism , Hair/growth & development , Light , Low-Level Light Therapy/methods , Rhodopsin/metabolism , Rod Opsins/metabolism , Adult , Aged , Alopecia/physiopathology , Apoptosis , Biomarkers/metabolism , Cell Proliferation , Female , Hair Follicle/physiology , Humans , In Vitro Techniques , Male , Middle AgedABSTRACT
No disponible
Subject(s)
Humans , Female , Hair/physiopathology , Puerperal Disorders/physiopathology , Quality of Life , Hair Follicle/physiopathology , Micronutrients/therapeutic use , Alopecia/physiopathology , Breast Feeding , Amino Acids, Sulfur/therapeutic use , Zinc/therapeutic use , Iron/therapeutic use , Water-Soluble Vitamins/administration & dosage , Dietary SupplementsABSTRACT
Leucaena (Leucaena leucocephala) is a leguminous tree that is nutritious forage for domestic livestock when ingested in limited amounts. Unfortunately, leucaena contains mimosine, a plant amino acid, that can be toxic when ingested at higher concentrations. Reported toxic effects include alopecia (fur loss), poor body condition, infertility, low birth weight, thyroid gland dysfunction, and organ toxicity. Originally native to Mexico and Central America, leucaena has been introduced throughout the tropics, including Berenty Reserve, Madagascar where it was planted as supplemental browse for livestock. In Berenty, a seasonal syndrome of alopecia in ringtailed lemurs (Lemur catta) is associated with eating leucaena. Although much is known about the toxic effects of leucaena and mimosine on domestic animals and humans, the systemic effects on wildlife had not been studied. In a comparison of lemurs that include leucaena in their diet and those that do not, we found that animals that ingest leucaena absorb mimosine but that ingestion does not affect body condition, cause kidney or liver toxicity, or affect the intestinal tract. Alopecia is due to mimosine's interference of the hair follicle cycle. Leucaena ingestion is associated with higher serum albumin, α-tocopherol, and thyroxine concentrations, suggesting that leucaena may provide some nutritional benefit and that lemurs can detoxify and convert mimosine to a thyroid stimulating metabolite. The primary conservation consequence of leucaena ingestion at Berenty may be increased infant mortality due to the infants' inability cling to their alopecic mothers. The widespread introduction of leucaena throughout the tropics and its rapid spread in secondary forest conditions mean that many other leaf-eating mammals may be including this tree in their diet. Thus, exposure to leucaena should be considered when wildlife health is being evaluated, and the potential effects on wildlife health should be considered when contemplating leucaena introduction into or near wildlife habitat.
Subject(s)
Alopecia/veterinary , Fabaceae/toxicity , Lemur , Mimosine/toxicity , Alopecia/chemically induced , Alopecia/physiopathology , Animals , Diet/veterinary , Female , Hair/physiopathology , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Madagascar , Male , Mimosine/metabolism , Serum Albumin/metabolism , Thyroxine/blood , alpha-Tocopherol/bloodABSTRACT
INTRODUCTION: Hair loss or alopecia affects the majority of the population at some time in their life, and increasingly, sufferers are demanding treatment. Three main types of alopecia (androgenic [AGA], areata [AA] and chemotherapy-induced [CIA]) are very different, and have their own laboratory models and separate drug-discovery efforts. AREAS COVERED: In this article, the authors review the biology of hair, hair follicle (HF) cycling, stem cells and signaling pathways. AGA, due to dihydrotesterone, is treated by 5-α reductase inhibitors, androgen receptor blockers and ATP-sensitive potassium channel-openers. AA, which involves attack by CD8(+)NK group 2D-positive (NKG2D(+)) T cells, is treated with immunosuppressives, biologics and JAK inhibitors. Meanwhile, CIA is treated by apoptosis inhibitors, cytokines and topical immunotherapy. EXPERT OPINION: The desire to treat alopecia with an easy topical preparation is expected to grow with time, particularly with an increasing aging population. The discovery of epidermal stem cells in the HF has given new life to the search for a cure for baldness. Drug discovery efforts are being increasingly centered on these stem cells, boosting the hair cycle and reversing miniaturization of HF. Better understanding of the molecular mechanisms underlying the immune attack in AA will yield new drugs. New discoveries in HF neogenesis and low-level light therapy will undoubtedly have a role to play.
Subject(s)
Alopecia/drug therapy , Drug Discovery/methods , Hair/drug effects , Administration, Topical , Alopecia/etiology , Alopecia/physiopathology , Animals , Hair/growth & development , Hair Follicle/metabolism , Humans , Immunotherapy/methods , Pharmaceutical Preparations/administration & dosage , Stem Cells/cytologySubject(s)
Alopecia/therapy , Acupuncture Points , Acupuncture Therapy , Adolescent , Alopecia/physiopathology , Female , Hair/growth & development , HumansABSTRACT
Androgenetic alopecia (AGA) is the most common form of alopecia, affecting up to 80% of men and 50% of women in the course of their life. AGA is caused by a progressive reduction in the diameter, length and pigmentation of the hair. Hair thinning results from the effects of the testosterone metabolite dehydrotestosterone (DHT) on androgen-sensitive hair follicles. In women, AGA produces diffuse thinning of the crown region with maintenance of the frontal hairline (Ludwig pattern AGA). In premenopausal women, AGA can be a sign of hyperandrogenism, together with hirsutism and acnes. Male pattern is characterized by bitemporal recession of the frontal hairline, followed by diffuse thinning at the vertex. Today, scalp dermoscopy is used routinely in patients with androgenetic alopecia, as it facilitates the diagnosis and differential diagnosis with other diseases, allows staging of severity, and allows you to monitor the progress of the disease in time and response to treatment. AGA is a progressive disease that tends to worsen with time. Medical treatment of AGA includes topical minoxidil, antiandrogen agents, 5-alpha reductase inhibitors.
Subject(s)
Alopecia , 5-alpha Reductase Inhibitors/therapeutic use , Alopecia/diagnosis , Alopecia/drug therapy , Alopecia/epidemiology , Alopecia/etiology , Alopecia/physiopathology , Androgen Antagonists/therapeutic use , Biopsy , Comorbidity , Contraindications , Dermoscopy , Dietary Supplements , Female , Hair Follicle/pathology , Hirsutism/etiology , Humans , Hyperandrogenism/complications , Ketoconazole/therapeutic use , Male , Menopause , Minoxidil/adverse effects , Minoxidil/therapeutic use , Prognosis , Receptors, Androgen/metabolism , Scalp/pathology , Sex Characteristics , Testosterone/analogs & derivatives , Testosterone/metabolism , Virilism/complicationsABSTRACT
Zinc is a trace element essential to the gastrointestinal, immune, integumentary, reproductive, and central nervous systems. Zinc deficiency is prevalent in many areas of the world and is a diagnostically challenging condition. Cutaneous manifestations typically occur in moderate to severe zinc deficiency and present as alopecia and dermatitis in the perioral, acral, and perineal regions. Zinc deficiency is a potentially fatal disease process. The aim of this review is to focus on the cutaneous manifestations, diagnosis, and treatment of zinc deficiency in children, and to propose an etiologic classification system.
Subject(s)
Deficiency Diseases/diagnosis , Deficiency Diseases/therapy , Dietary Supplements , Zinc/deficiency , Acrodermatitis/etiology , Acrodermatitis/physiopathology , Acrodermatitis/therapy , Alopecia/etiology , Alopecia/physiopathology , Alopecia/therapy , Child , Child, Preschool , Deficiency Diseases/mortality , Dermatitis/etiology , Dermatitis/physiopathology , Dermatitis/therapy , Female , Humans , Infant , Male , Malnutrition/complications , Pediatrics , Prognosis , Risk Assessment , Survival Rate , Treatment Outcome , Zinc/metabolismABSTRACT
Since the 1980s, laser technology has become increasingly popular to treat a variety of cutaneous conditions. Its successful use as an epilator comes with the rare but interesting side effect of paradoxical hypertrichosis. In this review, we summarize cases describing hair growth after photoepilation, as well as studies testing laser and light sources as treatment for alopecia, particularly androgenetic alopecia and alopecia areata. We also discuss the possible biologic mechanisms by which phototherapy induces hair regeneration.
Subject(s)
Alopecia/therapy , Hair Removal/adverse effects , Hair/physiology , Hypertrichosis/etiology , Laser Therapy/adverse effects , Phototherapy/adverse effects , Regeneration , Alopecia/physiopathology , Female , Hair/transplantation , Humans , Hypertrichosis/physiopathology , MaleABSTRACT
Crude drugs expected to have an estrogenic effect were screened for their inhibitory activity on testosterone 5α-reductase. Testosterone 5α-reductase is an enzyme catalyzing the conversion of testosterone to dihydrotestosterone, which possesses high affinity for the androgen receptor. Among the crude drugs tested, we focused on Puerariae Flos (the flowers of Pueraria thomsonii) due to its potent inhibitory activity and suitability for commercial use. The 50% ethanolic extract of Puerariae Flos (PF-ext) showed inhibitory activity of 60.2% at 500 µg/ml against testosterone 5α-reductase. Interestingly, it was more potent than that of Puerariae Radix (roots of Pueraria lobata). PF-ext also showed in vivo anti-androgenic activity using a hair growth assay in testosterone-sensitive male C57Black/6NCrSlc strain mice. We demonstrated saponins, including soyasaponin I and kaikasaponin III, to be active components in PF-ext. In addition, hair growth promotion activity in C3H/He mice at 2 mg/mouse/day of the topical administration of PF-ext was demonstrated. Thus, Puerariae Flos is a promising crude drug for treating androgenic alopecia.
Subject(s)
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism , 5-alpha Reductase Inhibitors/pharmacology , Alopecia/drug therapy , Androgen Antagonists/pharmacology , Drugs, Chinese Herbal/pharmacology , Hair/drug effects , Pueraria , 5-alpha Reductase Inhibitors/administration & dosage , 5-alpha Reductase Inhibitors/chemistry , 5-alpha Reductase Inhibitors/isolation & purification , Administration, Topical , Alopecia/enzymology , Alopecia/physiopathology , Androgen Antagonists/administration & dosage , Androgen Antagonists/chemistry , Androgen Antagonists/isolation & purification , Animals , Disease Models, Animal , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Ethanol/chemistry , Flowers , Hair/growth & development , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Plant Roots , Plants, Medicinal , Pueraria/chemistry , Rats , Rats, Wistar , Solvents/chemistry , Time FactorsABSTRACT
Hair has psychological and sociological importance throughout the ages in framing the personality and general appearance of an individual. Significant progress is being made on discovering an effective and safe drug for hair growth. Angiogenesis, androgen antagonism, vasodilation, potassium channel opening and 5-alpha reductase inhibition are the major non-surgical therapeutic strategies of hair growth promotion. In spite of a flood of drugs claiming to be useful as hair growth promoters, more rational strategies, which can target the problem areas or stages of the hair growth cycle effectively, are still awaited. This article highlights the developments in hair rejuvenation strategies and reviews the potential of herbal drugs as safer and effective alternatives.
Subject(s)
Alopecia/drug therapy , Alopecia/etiology , Alopecia/physiopathology , Female , Hair/growth & development , Humans , Male , RejuvenationABSTRACT
The use of herbal medications in dermatologic disease has become common practice among consumers. In this paper, the authors review and discuss the existing evidence-based botanical modalities in the peer-reviewed literature with a particular focus on various presentations of alopecia. To maximize potential clinical application, this review has been limited human studies. The goal of the study was to provide a thorough evaluation of the current understanding of the use of non-pharmaceutical botanical products in the management of hair loss.
Subject(s)
Alopecia/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Alopecia/etiology , Alopecia/physiopathology , Alopecia Areata/drug therapy , Animals , Antineoplastic Agents/adverse effects , Humans , Plant Extracts/chemistryABSTRACT
Vitamin D-dependent rickets type II (VDDR-type II) is a rare disorder caused by mutations in the vitamin D receptor (VDR) gene. Here, we describe a patient with VDDR-type II with severe alopecia and rickets. She had hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and elevated serum alkaline phosphatase and 1,25-dihydroxyvitamin D(3). Sequence analysis of the lymphocyte VDR cDNA revealed deletion mutation c.716delA. Sequence analysis of her genomic DNA fragment amplified from exon 6 of the VDR gene incorporating this mutation confirmed the presence of the mutation in homozygous form. This frameshift mutation in the ligand binding domain (LBD) resulted in premature termination (p.Lys240Argfs) of the VDR protein. The mutant protein contained 246 amino acids, with 239 normal amino acids at the N terminus, followed by seven changed amino acids resulting in complete loss of its LBD. The mutant VDR protein showed evidence of 50% reduced binding with VDR response elements on electrophoretic mobility assay in comparison to the wild-type VDR protein. She was treated with high-dose calcium infusion and oral phosphate. After 18 months of treatment, she gained 6 cm of height, serum calcium and phosphorus improved, alkaline phosphatase levels decreased, and intact PTH normalized. Radiologically, there were signs of healing of rickets. Her parents and one of her siblings had the same c.716delA mutation in heterozygous form. Despite the complete absence of LBD, the rickets showed signs of healing with intravenous calcium.
Subject(s)
Familial Hypophosphatemic Rickets/genetics , Familial Hypophosphatemic Rickets/metabolism , Genetic Predisposition to Disease/genetics , Mutation/genetics , Receptors, Calcitriol/genetics , Adolescent , Alkaline Phosphatase/blood , Alopecia/genetics , Alopecia/metabolism , Alopecia/physiopathology , Amino Acid Sequence/genetics , Base Sequence , Calcitriol/blood , Calcium/pharmacology , Calcium/therapeutic use , Codon, Nonsense/genetics , DNA Mutational Analysis , Familial Hypophosphatemic Rickets/drug therapy , Female , Frameshift Mutation/genetics , Gene Deletion , Genetic Markers , Humans , Hyperparathyroidism/genetics , Hyperparathyroidism/metabolism , Hyperparathyroidism/physiopathology , Hypocalcemia/genetics , Hypocalcemia/metabolism , Hypocalcemia/physiopathology , Hypophosphatemia/genetics , Hypophosphatemia/metabolism , Hypophosphatemia/physiopathology , Phosphates/pharmacology , Phosphates/therapeutic use , Protein Structure, Tertiary/genetics , Receptors, Calcitriol/chemistry , Receptors, Calcitriol/metabolism , Recovery of Function/physiology , Treatment OutcomeABSTRACT
Androgen-inducible transforming growth factor beta (TGF-beta1) derived from dermal papilla cells (DPCs) is a catagen inducer that mediates hair growth suppression in androgenetic alopecia (AGA). In this study, a cell-based assay system was developed to monitor TGF-beta1 promoter activity and then used to evaluate the effects of activated TGF-beta1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-beta1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-beta1 promoter activity was constructed. Treatment of HaCaT with dihydrotestosterone, which is known to be a primary factor of AGA, resulted in a concentration-dependent increase in TGF-beta1 promoter activity. However, treatment of HaCaT with the TGF-beta1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-beta1 expression. Subsequent use of this assay system to screen TGF-beta1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-beta1 expression. In addition, treatment with apigenin also significantly increased the proliferation of both SV40T-DPCs (human DPCs) and HaCaT cells. Furthermore, apigenin stimulated the elongation of hair follicles in a rat vibrissa hair follicle organ culture. Taken together, these findings suggest that apigenin, which is known to have antioxidant, anti-inflammatory, and anti-tumor properties, stimulates hair growth through downregulation of the TGF-beta1 gene. In addition, these results suggest that this assay system could be used to quantitatively measure TGF-beta1 promoter activity in HaCaT, thereby facilitating the screening of agents promoting hair growth.
Subject(s)
Alopecia/immunology , Drug Evaluation, Preclinical/methods , Hair/metabolism , Immunotherapy , Keratinocytes/metabolism , Transforming Growth Factor beta1/metabolism , Vibrissae/metabolism , Alopecia/pathology , Alopecia/physiopathology , Alopecia/therapy , Animals , Apigenin/pharmacology , Cell Culture Techniques , Cell Growth Processes/drug effects , Cell Growth Processes/immunology , Curcumin/pharmacology , Epidermis/pathology , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Hair/drug effects , Hair/growth & development , Hair/immunology , Humans , Keratinocytes/drug effects , Keratinocytes/immunology , Keratinocytes/pathology , Promoter Regions, Genetic , Rats , Transcriptional Activation/drug effects , Transcriptional Activation/immunology , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/immunology , Vibrissae/drug effects , Vibrissae/immunology , Vibrissae/pathologyABSTRACT
OBJECTIVE: To investigate the possible stimulating mechanism of Huoxue Bushen Mixture (HXBSM), a traditional Chinese compound medicine, on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle. METHODS: Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen. Ninety C57BL/6 mice were divided into 3 groups randomly: HXBSM group, Yangxue Shengfa Capsule (YXSFC, another traditional Chinese compound medicine) group and untreated group. The mice were fed with corresponding drugs after modeling. The hair growth of the mice was observed every day. Every ten mice out of each group were executed respectively at day 4, 11 and day 17. Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method. RESULTS: The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 (P<0.05); and evidently larger than that in the YXSFC group and the untreated group at day 11 (P<0.05). The expression of VEGF in the hair follicle was distinctively higher than that in the YXSFC group and the untreated group at day 11 and day 17 (P<0.05). CONCLUSION: HXBSM up-regulates VEGF expression to accelerate blood vessel neogenesis and hair growth.