RESUMO
People with primary focal hyperhidrosis (PFH) usually have an overactive sympathetic nervous system, which can activate the sweat glands through the chemical messenger of acetylcholine. The role of aquaporin 5 (AQP5) and Na-K-2Cl cotransporter 1 (NKCC1) in PFH is still unknown. The relative mRNA and protein levels of AQP5 and NKCC1 in the sweat gland tissues of three subtypes of patients with PFH (primary palmar hyperhidrosis, PPH; primary axillary hyperhidrosis, PAH; and primary craniofacial hyperhidrosis, PCH) were detected with real-time PCR (qPCR) and Western blot. Primary sweat gland cells from healthy controls (NPFH-SG) were incubated with different concentrations of acetylcholine, and the relative mRNA and protein expression of AQP5 and NKCC1 were also detected. NPFH-SG cells were also transfected with si-AQP5 or shNKCC1, and acetylcholine stimulation-induced calcium transients were assayed with Fluo-3 AM calcium assay. Upregulated AQP5 and NKCC1 expression were observed in sweat gland tissues, and AQP5 demonstrated a positive Pearson correlation with NKCC1 in patients with PPH (r = 0.66, P < 0.001), patients with PAH (r = 0.71, P < 0.001), and patients with PCH (r = 0.62, P < 0.001). Upregulated AQP5 and NKCC1 expression were also detected in primary sweat gland cells derived from three subtypes of patients with PFH when compared with primary sweat gland cells derived from healthy control. Acetylcholine stimulation could induce the upregulated AQP5 and NKCC1 expression in NPFH-SG cells, and AQP5 or NKCC1 inhibitions attenuated the calcium transients induced by acetylcholine stimulation in NPFH-SG cells. The dependence of ACh-stimulated calcium transients on AQP5 and NKCC1 expression may be involved in the development of PFH.NEW & NOTEWORTHY The dependence of ACh-stimulated calcium transients on AQP5 and Na-K-2Cl cotransporter 1 (NKCC1) expression may be involved in the development of primary focal hyperhidrosis (PFH).
Assuntos
Aquaporina 5 , Hiperidrose , Humanos , Acetilcolina/farmacologia , Acetilcolina/metabolismo , Aquaporina 5/genética , Aquaporina 5/metabolismo , Cálcio/metabolismo , Técnicas de Cultura de Células , Hiperidrose/metabolismo , RNA Mensageiro/metabolismo , Glândulas Sudoríparas/química , Glândulas Sudoríparas/metabolismoRESUMO
BACKGROUND: Primary focal hyperhidrosis (PFH) may be attributed to the up-regulation of the cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in eccrine glands. Plasminogen activator inhibitor-1 (PAI1, encoded by SERPINE1) is reported to inhibit the expression of CHRNA1, while the role of PAI1 in hyperhidrosis is unknown. METHODS: Serpine1 KO mice, Serpine1-Tg mice, and wild type BALB/c mice were intraperitoneally injected with pilocarpine hydrochloride to induce PFH. Cisatracurium (CIS, antagonist of CHRNA1) or PAI-039 (small-molecule inhibitor of PAI1) was pre-administrated before the induction of hyperhidrosis. On the other hand, Chrna1-expressing AAV was constructed and administered to Serpine1-Tg mice with hydrochloride stimulation. Hydrochloride-related biomarkers, such as acetylcholine (ACH) in the serum, calcium voltage-gated channel subunit alpha1 C (CACNA1C), and aquaporin 5 (AQP5) in sweat glands of mice were assayed with ELISA, RT-PCR, and Western blot. RESULTS: The administration of PAI-039 or Pai1 knock-out increased Chrna1 expression, sweat secretion, and hydrochloride-related biomarkers (ACH, CACNA1C, and AQP5) expression. On the other hand, CIS administration diminished the strengthened hyperhidrosis phenotype induced by Pai1 knock-out with decreased sweat gland secretion. CONCLUSION: PAI1 inhibits CHRNA1-mediated hydrochloride-induced hyperhidrosis, with decreased sweat gland secretion and diminished ACH, AQP5, and CACNA1C expression. These results indicate the potential to utilize PAI1 to alleviate PFH.
Assuntos
Hiperidrose , Glândulas Sudoríparas , Animais , Camundongos , Acetilcolina/metabolismo , Aquaporina 5/genética , Aquaporina 5/metabolismo , Biomarcadores/metabolismo , Hiperidrose/genética , Hiperidrose/metabolismo , Hiperidrose/patologia , Glândulas Sudoríparas/metabolismo , Glândulas Sudoríparas/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismoRESUMO
BACKGROUND: The regulatory effect of integrin ß6 (ITGB6) on sweat gland cells in primary palmar hyperhidrosis (PPH) remains unclear. OBJECTIVES: This study investigated the involvement of ITGB6 in the pathogenesis of PPH. MATERIAL AND METHODS: Sweat gland tissues were collected from PPH patients and healthy volunteers. The expression levels of ITGB6 in sweat gland tissues were detected with quantitative polymerase chain reaction (qPCR), western blot and immunohistochemical staining. Sweat gland cells were extracted from PPH patients, and identified with immunofluorescence staining of CEA and CK7. The expression of aquaporin 5 (AQP5) and Na-K-Cl cotransporter 1 (NKCC1) in primary sweat gland cells that overexpress ITGB6 were also detected. Through a series of bioinformatic methods, differentially expressed genes in sweat gland tissues were examined and validated via comparing PPH samples and controls. The key proteins and biological functions enriched in PPH were determined using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: The ITGB6 was upregulated in sweat gland tissues of PPH patients compared to that of healthy volunteers. The CEA and CK7 were positively expressed in sweat gland cells extracted from PPH patients. The overexpression of ITGB6 upregulated AQP5 and NKCC1 protein expression in the sweat gland cells of PPH patients. A total of 562 differentially expressed mRNAs were identified using high-throughput sequencing (394 upregulated, 168 downregulated), which were mainly active in the chemokine and Wnt signaling pathways. After verification with qPCR and western blot, the overexpression of ITGB6 significantly upregulated CXCL3, CXCL5, CXCL10, and CXCL11, and downregulated Wnt2 mRNA and protein expression in sweat gland cells. CONCLUSIONS: The ITGB6 is upregulated in PPH patients. It may be involved in the pathogenesis of PPH by upregulating AQP5, NKCC1, CXCL3, CXCL5, CXCL10, and CXCL11, and downregulating Wnt2 expression in sweat glands.
Assuntos
Hiperidrose , Glândulas Sudoríparas , Humanos , Regulação para Cima , Glândulas Sudoríparas/metabolismo , Glândulas Sudoríparas/patologia , Cadeias beta de Integrinas/genética , Cadeias beta de Integrinas/metabolismo , Aquaporina 5/genética , Aquaporina 5/metabolismo , Hiperidrose/genética , Hiperidrose/metabolismo , Hiperidrose/patologiaRESUMO
The aim of the study was to elucidate the involvement of cholinergic receptor nicotinic alpha 1 subunit (CHRNA1) in the pathogenesis of primary focal hyperhidrosis (PFH). The hyperhidrosis mouse model was constructed using pilocarpine injection. The expression levels of CHRNA1 in sweat gland tissues of PFH patients and hyperhidrosis mice were compared using Western blots and quantitative real-time PCR (qRT-PCR) analyses. Sweat secretion in hyperhidrosis mice treated with small-interfering RNA (siRNA) targeting CHRNA1 (si-CHRNA1) or non-specific siRNA were compared. Sweat secretory granules in the sweat gland cells of hyperhidrosis mice were examined using transmission electron microscopy. The serum level of acetylcholine was measured using enzyme-linked immunosorbent assay, while markers associated with PFH, including Aquaporin 5 (AQP5) and Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C), were assessed using immunohistochemical assay and Western blots. Brain-derived neurotrophic factor (BDNF) and Neuregulin 1 (NRG-1) in sympathetic ganglia axons of hyperhidrosis mice were quantified using Western blots. CHRNA1 up-regulation is a characteristic of the sweat glands of PFH patients and Hyperhidrosis mice. Silencing CHRNA1 decreased sweat secretion and the number of sweat secretory granules of hyperhidrosis mice. Serum acetylcholine, as well as AQP5 and CACNA1C expression in the sweat glands, was reduced by siCHRNA1. BDNF1 and NRG-1 levels in the sympathetic ganglia axons were also attenuated by siCHRNA1 treatment. CHRNA1 up-regulation is a potential biomarker of PFH and downregulating CHRNA1 could alleviate the symptoms of PFH through inactivating the sympathetic system.
Assuntos
Hiperidrose/metabolismo , Receptores Nicotínicos/metabolismo , Glândulas Sudoríparas/metabolismo , Acetilcolina/sangue , Animais , Aquaporina 5/genética , Aquaporina 5/metabolismo , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Humanos , Hiperidrose/genética , Camundongos , Camundongos Endogâmicos BALB C , Receptores Nicotínicos/genéticaRESUMO
The pathogenesis of primary focal hyperhidrosis (PFH) is still not clear. PFH is thought to be a genetic disease. Whether activin A receptor type 1 (ACVR1) is involved in the pathogenesis of PFH is unknown. In this study, the expression of ACVR1 in sweat glands of patients with PAH was detected by western blot and immunofluorescence. The primary sweat gland cells obtained from primary axillary hyperhidrosis (PAH) patients were transfected with acvr1 vector. Cell proliferation, apoptosis and cell cycling of gland cells were measured after transfection with acvr1 vector. The mRNA and protein expression of aquaporin 5 (AQP5) and Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) were detected. Our data showed that ACVR1 expression in axillary sweat gland tissue of PAH patients was significantly higher than that of normal control group. The function of ACVR1 was further investigated in the gland cells obtained from PAH patients. Compared with NC group, ACVR1 overexpression significantly promoted the proliferation of sweat gland cells and inhibited the apoptosis of sweat gland cells. Meanwhile, ACVR1 overexpression significantly reduced the percentage of cells in G0/G1 and G2/M phases, and increased the percentage of cells in S phase. In addition, ACVR1 overexpression significantly promoted the expression of AQP5 and NKCC1 at both mRNA and protein levels. Together, ACVR1 expression is related to PFH and ACVR1 overexpression can promote the proliferation of sweat gland cells and inhibit apoptosis by promoting the expression of AQP5 and NKCC1.
Assuntos
Receptores de Ativinas Tipo I/metabolismo , Hiperidrose/metabolismo , Hiperidrose/patologia , Apoptose , Aquaporina 5/genética , Aquaporina 5/metabolismo , Proliferação de Células , Regulação da Expressão Gênica , Humanos , Hiperidrose/genética , Membro 2 da Família 12 de Carreador de Soluto/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo , Glândulas Sudoríparas/metabolismo , Glândulas Sudoríparas/patologiaAssuntos
Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/genética , Hiperidrose/diagnóstico , Hiperidrose/genética , Receptores de Citocinas/genética , Trismo/congênito , Morte Súbita , Fácies , Deformidades Congênitas da Mão/metabolismo , Humanos , Hiperidrose/metabolismo , Lactente , Recém-Nascido , Masculino , Receptores de Citocinas/metabolismo , Deleção de Sequência/genética , Trismo/diagnóstico , Trismo/genética , Trismo/metabolismoRESUMO
BACKGROUND: We investigated the safety and feasibility of intraoperative near-infrared (NIR) imaging using indocyanine green (ICG) during sympathectomy in the management of primary palmar hyperhidrosis (PPH). METHODS: We performed a retrospective review of 142 patients (ICG group) who underwent endoscopic thoracic sympathectomy (ETS) between February 2018 and April 2019. All patients received a 5 mg/kg infusion of ICG 24 hours preoperatively. The vital signs before and after ICG injection and adverse reactions were recorded. Meanwhile, 498 patients (Non-ICG group) who underwent ETS by normal thoracoscopy during August 2017 to April 2019 were also reviewed to compare the abnormal white blood cell (WBC) counts, alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine (Cr) levels before and after operation between two groups. RESULTS: For ICG group, the vital signs including body temperature, heart rate and blood pressure before and after ICG injection were stable. There was no significant difference in the abnormal WBC counts, ALT, AST, BUN, and Cr levels before and after operation between two groups. Only one patient had mild adverse reaction (0.7%) after ICG injection. The visibility rate of all sympathetic ganglions was 96.7% (1369/1415). The visibility rate from T1 to T5 was 98.23% (278/283), 98.23% (278/283), 97.17% (275/283), 95.76% (271/283), and 94.35% (267/283), respectively. There was no significant difference in the visibility rate with regard to age, gender, height, weight, body mass index, and PPH grade. CONCLUSIONS: NIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible. KEY POINTS: ⢠Significant findings of the study. NIR fluorescence imaging with ICG for identifying sympathetic ganglions is relatively safe and feasible. ⢠What this study adds. This technology may take the place of the rib-oriented method as standard practice for the precise localization of sympathetic ganglions, and may improve the effect of sympathectomies.
Assuntos
Hiperidrose/cirurgia , Verde de Indocianina/metabolismo , Cuidados Intraoperatórios , Imagem Óptica/métodos , Simpatectomia/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Toracoscopia/métodos , Adulto , Estudos de Viabilidade , Feminino , Fluorescência , Seguimentos , Humanos , Hiperidrose/diagnóstico por imagem , Hiperidrose/metabolismo , Hiperidrose/patologia , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
This represents part 2 of a 2-part article on the topic of primary focal hyperhidrosis. Part 1, which was published in the International Journal of Pharmaceutical Compounding's January/February 2019 issue, provided a comprehensive review of the active pharmaceutical ingredients aluminum salts and methenamine in the treatment of primary focal hyperhidrosis. Part 2 provides a comprehensive review of the active pharmaceutical ingredients glycopyrronium salts and oxybutynin chloride in the treatment of primary focal hyperhidrosis.
Assuntos
Administração Tópica , Hiperidrose , Humanos , Hiperidrose/metabolismoAssuntos
Axila , Antagonistas Colinérgicos/administração & dosagem , Glicopirrolato/administração & dosagem , Hiperidrose/tratamento farmacológico , Administração Tópica , Antagonistas Colinérgicos/farmacocinética , Glicopirrolato/farmacocinética , Humanos , Hiperidrose/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
Klippel-Trenaunay syndrome (KTS) is a rare, clinically variable congenital disorder involving capillary malformations, soft tissue or bone hypertrophy, and venous malformations or varicose veins. We report a 28-year-old man who presented with a hypertrophic right arm as well as markedly increased ipsilateral axillary hyperhidrosis and erythematous patches on the back, chest, and arm. This case of KTS is unusual because our patient presented with a markedly increased unilateral axillary hyperhidrosis ipsilateral to the hypertrophic limb.
Assuntos
Hiperidrose/complicações , Síndrome de Klippel-Trenaunay-Weber/complicações , Adulto , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Humanos , Hiperidrose/metabolismo , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Masculino , Redes e Vias Metabólicas , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: The expression of aquaporin 5 (AQP5) in human axillary sweat glands has never been studied so far. OBJECTIVE: To detect the expression of AQP5 in axillary sweat glands of patients with primary focal hyperhidrosis (PFH) relative to control subjects. METHODS: The morphological characteristics and the number of sweat coils in axillary sweat glands were compared between two groups by using transmission electron microscopy. The expression of AQP5 was detected by immunohistochemistry, Western blot analysis, and real-time transcription polymerase chain reaction. RESULTS: There were no significant differences between the two groups in terms of morphological characteristics and the number of sweat coils in axillary sweat glands. The expressions of AQP5 protein and AQP5 mRNA were significantly higher in the patient group than in the control group. CONCLUSION: AQP5 is involved in the secretion of human axillary sweat glands. The overexpression of AQP5 in sweat glands is probably one pathogenetic mechanism underlying PFH.
Assuntos
Aquaporina 5/análise , Hiperidrose/metabolismo , RNA Mensageiro/análise , Glândulas Sudoríparas/química , Adolescente , Adulto , Aquaporina 5/genética , Axila , Estudos de Casos e Controles , Feminino , Humanos , Hiperidrose/genética , Hiperidrose/patologia , Masculino , Microscopia Eletrônica de Transmissão , Glândulas Sudoríparas/ultraestrutura , Adulto JovemRESUMO
BACKGROUND: Hyperhidrosis (HH) is a disease whose physiopathology remains poorly understood and that adversely affects quality of life. There is no morphologic study that includes an adequate control group that allows for comparison of the ganglion of HH to those of normal individuals. The purpose of study was to analyze morphologic and morphometric characteristics of the ganglion from patients with HH and normal individuals (organ donators). METHODS: This was a transversal study. The sympathetic thoracic ganglia were obtained from 2 groups of patients. Group PH (palmar hyperhidrosis), 40 patients with palmar HH submitted to surgery by video-assisted thoracoscopy, and group C (control group), 14 deceased individuals (control group of organ donators) without any history of HH. The third left sympathetic thoracic ganglion was resected in all patients. RESULTS: We observed higher number of cells in the PH group than in the control group (14.25 + 3.81 vs. 10.65 + 4.93) with P = 0.007; the mean percentage of ganglion cells stained by caspases-3 in the PH group was significantly greater than that of the C group (2.37 + 0.79 vs. 0.77 + 0.28) with P < 0.001; the mean value of area of collagen in the PH group was 0.80 IQ (0.08-1.87), and in the control group it was 2.36 IQ (0.49-5.98) with P = 0.061. CONCLUSIONS: Subjects with primary palmar HH have a higher number of ganglion cells within the ganglion and a higher number of cells in apoptosis. Also, the subjects of PH group have less collagen in the sympathetic ganglion when compared with the control group, but not statistically significant.
Assuntos
Gânglios Simpáticos/patologia , Hiperidrose/patologia , Nervos Torácicos/patologia , Adolescente , Adulto , Idoso , Apoptose , Estudos de Casos e Controles , Criança , Colágeno/análise , Estudos Transversais , Feminino , Gânglios Simpáticos/química , Gânglios Simpáticos/cirurgia , Humanos , Hiperidrose/metabolismo , Hiperidrose/cirurgia , Masculino , Pessoa de Meia-Idade , Simpatectomia/métodos , Nervos Torácicos/química , Nervos Torácicos/cirurgia , Cirurgia Torácica Vídeoassistida , Adulto JovemRESUMO
INTRODUCTION: Cold-induced sweating syndrome type 1 (CISS1) is a rare autosomal recessive genodermatosis caused by mutations in the CRLF1 gene, characterized by profuse sweating when the ambient temperature is below 22°C and morphological alterations. CRLF1 mutations also cause Crisponi syndrome (CS), which presents neonatal muscle contractions, morphological disorders and alterations in the autonomous nervous system. CASE REPORT: A 30-year-old man sought treatment for profuse sweating. His medical record included neonatal admission for generalized hypertonicity. Clinical examination revealed morphological alterations. A genetic study was requested, detecting a c.713dupC mutation in homozygosity in the CRLF1 gene. CONCLUSIONS: We report the case of a male with clinical and genetic diagnosis of CISS1 who in childhood presented clinical characteristics of CS. The mutation detected in CRLF1 has not been described in patients with CISS1, but in one with CS. These data seem to support the theory that CS and CISS1 are variants of the same disorder.
Assuntos
Anormalidades Múltiplas/genética , DNA/metabolismo , Febre/genética , Deformidades Congênitas da Mão/genética , Hiperidrose/genética , Mutação , Receptores de Citocinas/genética , Trismo/congênito , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/fisiopatologia , Adulto , Análise Mutacional de DNA , Morte Súbita , Fácies , Febre/metabolismo , Deformidades Congênitas da Mão/metabolismo , Homozigoto , Humanos , Hiperidrose/metabolismo , Hiperidrose/fisiopatologia , Masculino , Contração Muscular/genética , Receptores de Citocinas/metabolismo , Sudorese , Trismo/genética , Trismo/metabolismoRESUMO
BACKGROUND: Focal hyperhidrosis can severely affect quality of life. So far, knowledge on the effect of systemic therapy of focal hyperhidrosis is limited. OBJECTIVE: To assess the efficacy and safety of methantheline bromide (MB) in the treatment of axillary and palmar-axillary hyperhidrosis. METHODS: A multicenter controlled randomized double-blind clinical trial was conducted in patients with axillary or palmar-axillary hyperhidrosis defined by a sweat production >50 mg/5 min. Patients received 3 × 50 mg MB daily or placebo over a period of 28 ± 1 days. Main outcome criterion was the reduction of sweat as measured by gravimetry on day 28 ± 1. Quality of life was assessed by Dermatology Life Quality Index (DLQI) and Hyperhidrosis Disease Severity Score (HDSS). RESULTS: A total of 339 patients were randomly assigned to receive MB or placebo. On day 28 ± 1, the mean axillary sweat production was 99 mg for MB and 130 mg for placebo compared with 168 mg and 161 mg respectively at baseline (P = 0.004). Patient's HDSS score decreased in the MB group from 3.2 to 2.4 compared with 3.2 to 2.7 for placebo (P = 0.002). Similar results could be obtained for the DLQI with 9.7 for MB and 12.2 for placebo, which decreased from 16.4 or 17 respectively (P = 0.003). Tolerability was good for both groups. The most frequent adverse event was dry mouth. CONCLUSION: Fifty milligrams methantheline bromide three times a day is an effective and safe treatment of axillary hyperhidrosis.
Assuntos
Axila , Hiperidrose/tratamento farmacológico , Placa Palmar , Compostos de Amônio Quaternário/efeitos adversos , Compostos de Amônio Quaternário/uso terapêutico , Adolescente , Adulto , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hiperidrose/metabolismo , Masculino , Metantelina , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Suor/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The pathophysiologic characteristics of primary hyperhidrosis are not well understood and seem to be related to a sympathetic nervous system dysfunction. The resection of thoracic sympathetic chain ganglia is the most effective treatment for hyperhidrosis; however sympathetic ganglia function in normal individuals and in patients with hyperhidrosis is unknown. METHODS: A cross-sectional study, in which 2 groups of 20 subjects were analyzed: the hyperhidrosis group (HYP), comprised of patients with hyperhidrosis who were eligible for thoracic sympathectomy, and the control group (CON) comprised of brain-dead organ donors without a history of hyperhidrosis. For each subject, the following were performed: resection of the third left sympathetic ganglion, measurement of the ganglion's diameter, and immunohistochemical evaluation by quantification of strong and weak expression areas of primary antibodies against acetylcholine and alpha-7 neuronal nicotinic receptor subunit. RESULTS: The presence of a strong alpha-7 subunit expression area was 4.85% in patients with primary hyperhidrosis and 2.34% in controls (p < 0.001), whereas the presence of a weak expression area was 11.48% in the HYP group and 4.59% in the CON group (p < 0.001). Strong acetylcholine expression was found in 4.95% of the total area in the HYP group and in 1.19% in the CON group (p < 0.001), whereas weak expression was found in 18.55% and 6.77% of the HYP and CON groups, respectively (p < 0.001). Furthermore, diameter of the ganglia was 0.71 cm in the HYP group and 0.53 cm in the CON group (p < 0.001). CONCLUSIONS: There is a higher expression of acetylcholine and alpha-7 neuronal nicotinic receptor subunit in the sympathetic ganglia of patients with hyperhidrosis. Furthermore, the diameter of the thoracic sympathetic chain ganglia is larger in such patients.
Assuntos
Acetilcolina/biossíntese , Gânglios Simpáticos/metabolismo , Hiperidrose/metabolismo , Receptores Colinérgicos/biossíntese , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Primary palmar hyperhidrosis (PPH) is a condition characterized by high levels of palmar perspiration in excess of physiological need. The etiopathogenesis of PPH is thought to be related to hyperactivity of the sympathetic system, but the exact mechanism is still obscure. The aim of this study was to observe the ultrastructure of the thoracic sympathetic nerves and measure the expression of neuregulin-1 (Nrg-1) in thoracic sympathetic nerve tissue in patients with PPH relative to control subjects. Samples of T3 sympathetic ganglia were obtained from 58 subjects: 30 PPH patients who underwent endoscopic thoracic sympathectomy and 28 control subjects who underwent pleurectomy for chronic empyema. The ultrastructure of the myelin sheath of the sympathetic axons was observed using electron microscopy, and the thickness of the myelin sheath was compared between the two groups. Expression of Nrg-1 mRNA in thoracic sympathetic nerve tissue was evaluated using reverse transcription-polymerase chain reaction analysis. Subjects in the hyperhidrosis group had a significantly greater average myelin thickness and a significantly lower g-ratio relative to the control group. The hyperhidrosis group had significantly higher relative expression of Nrg-1 mRNA in thoracic sympathetic nerve tissue. Hypermyelination of the thoracic sympathetic axons is probably one pathogenetic mechanism underlying PPH. Nrg-1 is likely to be an important cause of hypermyelination in thoracic sympathetic axons in patients with PPH.
Assuntos
Fibras Adrenérgicas/metabolismo , Fibras Adrenérgicas/ultraestrutura , Hiperidrose/metabolismo , Hiperidrose/patologia , Bainha de Mielina/ultraestrutura , Neuregulina-1/metabolismo , Adulto , Axônios/ultraestrutura , Feminino , Mãos , Humanos , Masculino , Microscopia Eletrônica de Transmissão , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Simpatectomia , Adulto JovemRESUMO
BACKGROUND: Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods. OBJECTIVE: The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters. METHODS: 52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones. RESULTS: The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment. CONCLUSION: The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.
Assuntos
Acromegalia/fisiopatologia , Sebo/metabolismo , Fenômenos Fisiológicos da Pele , Suor , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hiperidrose/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pele/metabolismo , Temperatura Cutânea , Temperatura , Fatores de TempoRESUMO
Primary hyperhidrosis is characterized by excessive sweating in palmar, plantar and axillary body regions. Gland hypertrophy and the existence of a third type of sweat gland, the apoeccrine gland, with high fluid transporting capabilities have been suggested as possible causes. This study investigated whether sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis.
Assuntos
Glândulas Écrinas/citologia , Células Epiteliais/metabolismo , Hiperidrose/metabolismo , Suor/metabolismo , Glândulas Apócrinas/anatomia & histologia , Glândulas Apócrinas/citologia , Glândulas Apócrinas/metabolismo , Aquaporina 5/metabolismo , Axila/anatomia & histologia , Anidrase Carbônica II/metabolismo , Glândulas Écrinas/anatomia & histologia , Glândulas Écrinas/metabolismo , Células Epiteliais/citologia , Fucosiltransferases/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Hiperidrose/etiologia , Hiperidrose/patologia , Hipertrofia/patologia , Antígenos CD15/metabolismo , Proteínas S100/metabolismo , Simportadores de Cloreto de Sódio-Potássio/metabolismo , Membro 2 da Família 12 de Carreador de Soluto , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
Various treatments are currently available for palmoplantar hyperhidrosis. We have treated palmoplantar hyperhidrosis patients effectively with the use of alternating current (AC) iontophoresis. However, much remains unknown about the physiological changes that occur with AC iontophoresis, and its mechanism of action. We measured the changes in Na(+), K(+) concentration in perspiration and perspiration volume with AC iontophoresis in palmoplantar hyperhidrosis patients. We found that hyperhidrosis patients have significantly higher perspiration volume and Na(+) concentration in perspiration than healthy controls. Looking at the temporal changes with AC iontophoresis, we found a significant decrease in perspiration volume and Na(+) concentration in perspiration after six iontophoresis treatments. This result is further evidence that Na(+) concentration in perspiration is closely involved with perspiration volume. However, looking at the changes in perspiration volume and Na(+) concentration in perspiration before and after a single AC iontophoresis treatment, we found that while perspiration volume did not decrease in hyperhidrosis patients after a single treatment, there was a significant decrease in Na(+) concentration. In healthy controls as well, Na(+) concentration in perspiration decreased significantly after a single treatment. These findings suggest that the effect of AC iontophoresis may be due to a complex mechanism involving changes in reabsorption of ductal Na(+).