Efficacy and Safety of Scalp Microneedling in Male Pattern Hair Loss.

Introduction: There are few reports involving scalp microneedling in MPHL patients, and in most of them, physical stimulus is associated with other therapeutic agents. The aim of this study was to evaluate the efficacy and risks of isolated scalp microneedling in MPHL patients. Methods: Thirty patients were included in this randomized single-blinded study and submitted to 4 monthly scalp microneedling sessions. Two different microneedling devices were used: roller (n = 15) and tattoo cartridge (n = 15). Scalp coverage and hair density changes were measured 4 and 16 weeks after the last session. Adverse events were observed throughout the study, and scalp biopsies were performed before and after to investigate scarring changes. Results: Four of 12 participants in the roller group and 2 of 14 participants in the tattoo cartridge group showed an improvement in clinical pictures at the first follow-up visit. Only half of these patients sustained an improvement until the last follow-up visit. No benefit in hair density was observed in either group. No reports of adverse events were made. Neocollagenesis and elastolysis were noted in scalp biopsies. Discussion/Conclusion: Isolated scalp microneedling did not show improvement in scalp coverage or hair density of MPHL participants in this study.

Successful Treatment of Alopecia Areata Patches with Triamcinolone Acetonide Using MMP®: Report of 2 Cases.

Intralesional (IL) injection of corticosteroids is an effective treatment of alopecia areata (AA). A novel drug delivery technique that uses a tattoo machine (MMP®) has been successfully used to treat other skin disorders. We tested this technique to treat AA. We used the Cheyenne dermopigmentation machine (Anvisa 80281110016; Germany) with a 27 Magnum needle cartridge (Anvisa 80281110015) at a frequency of 70 Hz and needle depth of 1.0 mm. A triamcinolone acetonide (TAC) solution was placed in a sterile receptacle and loaded onto the cartridge by capillarity. We produced micropunctures of the skin with the medication-soaked needles until the affected area was covered by a bloody dew. Case 1: J.C.V., a male, with a diagnosis of AA in patches was treated with 1-monthly session with 2.5 mg/mL TAC delivered by MMP® (4 sessions in total). Case 2: L.M.V., a 78-year-old female with a diagnosis of AA was treated with 1-monthly session with 10 mg/mL TAC delivered by MMP® (4 sessions in total). MMP® is a novel technique that combines microneedling with drug delivery, and it could be used to deliver IL TAC to AA patients. This technique promotes a more uniform absorption of corticosteroids than traditional treatment methods of AA.

Utilização da técnica da prega para diminuir a dor no microagulhamento do couro cabeludo: estudo comparativo / Use of the pinch technique to reduce the pain in scalp microneedling: a comparative study

Introdução: O microgulhamento vem sendo realizado em diversas áreas da Dermatologia, incluíndo o tratamento da alopecia androgenética. Porém, um dos seus maiores limitantes é a dor, que ocorre tanto com o uso de cilindros agulhados, como com aparelhos motorizados dotados de microagulhas. Objetivo: descrever uma nova técnica para minimizar a dor durante o microagulhamento do couro cabeludo. Métodos: estudo observacional, prospectivo e comparativo, do microagulhamento realizado com aparelho motorizado, utilizando ou não o pregueamento da pele da área a ser tratada, entre os dedos polegar e indicador da mão não dominante do cirurgião. Este procedimento teve a denominação pelos autores, de Técnica da Prega. A dor foi avaliada pelo paciente com base em escala visual analógica, e os dados submetidos ao teste t-Student, a fim de verificar a existência de diferença estatística entre os dados analisados. Resultados: foram tratados 14 pacientes portadores de alopecia androgenética, 13 homens e 1 mulher. Após análise dos dados sobre a dor referida pelos pacientes, observou-se que a média aritmética dos dados das áreas não submetidas à Técnica da Prega era mais alta do que a média dos dados das áreas submetidas à referida técnica. Conclusões: A técnica descrita mostrou-se eficaz na diminuição da dor durante o procedimento de microagulhamento do couro cabeludo, em consequência da alteração da percepção dolorosa pelo estímulo tátil, e pelo distanciamento das agulhas em relação à gálea que é ricamente inervada.

Introduction: Microneedling has been performed in several areas of Dermatology, including the treatment of androgenetic alopecia. However, one of its major limitations is pain, which occurs both with the use of rollers with multiple fine needles and with motorized devices equipped with microneedles. Objective: To describe a new technique aimed at minimizing pain during the microneedling in the scalp. Methods: An observational, prospective and comparative study of the microneedling effects was performed with a motorized device, with and without folding the skin by using the thumb and index finger of the surgeon's non-dominant hand. This procedure was termed "pinch technique" by the authors. The pain was assessed by the patient based on a visual analogue scale, and the data analyzed with the Student's t-test, in order to verify the existence of statistical difference between the data sets. Results: Fourteen patients bearers of androgenetic alopecia (13 men and 1 woman) were treated. The analysis of the data on the pain reported by the patients suggested that the arithmetic mean of the data obtained from the areas where the technique was not applied was greater than that obtained in areas where the technique was employed. Conclusions: The described technique was proven effective in reducing pain during the microneedling procedure. That outcome resulted from the alteration of the perception of pain due to the tactile stimulus and the increase in the distance of the needles regarding the galea, which is richly innervated.

Pili Annulati and Trichorrhexis Nodosa in the Same Patient: Cause or Coincidence?

PURPOSE: To determine the relationship between pili annulati (PA) and acquired trichorrhexis nodosa (TN) seen in the same patient, considering the two main theories evoked by previous studies: greater stiffness of darker PA bands or associated cuticular damage. PROCEDURES: Light microscopy of hair shafts from different regions of the patient's scalp. RESULTS: TN was not superimposed to dark bands of PA. CONCLUSIONS: Greater stiffness of darker PA bands was excluded as the cause of hair breakage. Hair breakage in PA patients might be related to cuticular abnormalities, as previously reported. Because weathering of long thin chemically treated hairs is extremely common, coincidence cannot be completely ruled out in this case.

Clinical phenotype and functional characterization of CASQ2 mutations associated with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Four distinct mutations in the human cardiac calsequestrin gene (CASQ2) have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). The mechanisms leading to the clinical phenotype are still poorly understood because only 1 CASQ2 mutation has been characterized in vitro. METHODS AND RESULTS: We identified a homozygous 16-bp deletion at position 339 to 354 leading to a frame shift and a stop codon after 5aa (CASQ2(G112+5X)) in a child with stress-induced ventricular tachycardia and cardiac arrest. The same deletion was also identified in association with a novel point mutation (CASQ2(L167H)) in a highly symptomatic CPVT child who is the first CPVT patient carrier of compound heterozygous CASQ2 mutations. We characterized in vitro the properties of CASQ2 mutants: CASQ2(G112+5X) did not bind Ca2+, whereas CASQ2(L167H) had normal calcium-binding properties. When expressed in rat myocytes, both mutants decreased the sarcoplasmic reticulum Ca2+-storing capacity and reduced the amplitude of I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks in permeabilized myocytes. Exposure of myocytes to isoproterenol caused the development of delayed afterdepolarizations in CASQ2(G112+5X). CONCLUSIONS: CASQ2(L167H) and CASQ2(G112+5X) alter CASQ2 function in cardiac myocytes, which leads to reduction of active sarcoplasmic reticulum Ca2+ release and calcium content. In addition, CASQ2(G112+5X) displays altered calcium-binding properties and leads to delayed afterdepolarizations. We conclude that the 2 CASQ2 mutations identified in CPVT create distinct abnormalities that lead to abnormal intracellular calcium regulation, thus facilitating the development of tachyarrhythmias.

Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR(R4496C)) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR(R4496C) mice (P=0.02). Twenty-one mice (8 WT, 8 RyR(R4496C), and 5 RyR(R4496C) pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR(R4496C) mice but none of the WT developed VT (P=0.02); 4/5 RyR(R4496C) mice pretreated with propranolol developed VT (P=0.56 nonsignificant versus RyR(R4496C) mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.

A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene.

Short QT syndrome (SQTS) leads to an abbreviated QTc interval and predisposes patients to life-threatening arrhythmias. To date, two forms of the disease have been identified: SQT1, caused by a gain of function substitution in the HERG (I(Kr)) channel, and SQT2, caused by a gain of function substitution in the KvLQT1 (I(Ks)) channel. Here we identify a new variant, "SQT3", which has a unique ECG phenotype characterized by asymmetrical T waves, and a defect in the gene coding for the inwardly rectifying Kir2.1 (I(K1)) channel. The affected members of a single family had a G514A substitution in the KCNJ2 gene that resulted in a change from aspartic acid to asparagine at position 172 (D172N). Whole-cell patch-clamp studies of the heterologously expressed human D172N channel demonstrated a larger outward I(K1) than the wild-type (P<0.05) at potentials between -75 mV and -45 mV, with the peak current being shifted in the former with respect to the latter (WT, -75 mV; D172N, -65 mV). Coexpression of WT and mutant channels to mimic the heterozygous condition of the proband yielded an outward current that was intermediate between WT and D172N. In computer simulations using a human ventricular myocyte model the increased outward I(K1) greatly accelerated the final phase of repolarization, and shortened the action potential duration. Hence, unlike the known mutations in the two other SQTS forms (N588K in HERG and V307L in KvLQT1), simulations using the D172N and WT/D172N mutations fully accounted for the ECG phenotype of tall and asymmetrically shaped T waves. Although we were unable to test for inducibility of arrhythmia susceptibility due to lack of patients' consent, our computer simulations predict a steeper steady-state restitution curve for the D172N and WT/D172N mutation, compared with WT or to HERG or KvLQT1 mutations, which may predispose SQT3 patients to a greater risk of reentrant arrhythmias.

Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice.

Non-specific mental retardation (NSMR) is a common human disorder characterized by mental handicap as the only clinical symptom. Among the recently identified MR genes is GDI1, which encodes alpha Gdi, one of the proteins controlling the activity of the small GTPases of the Rab family in vesicle fusion and intracellular trafficking. We report the cognitive and behavioral characterization of mice carrying a deletion of Gdi1. The Gdi1-deficient mice are fertile and anatomically normal. They appear normal also in many tasks to assess spatial and episodic memory and emotional behavior. Gdi1-deficient mice are impaired in tasks requiring formation of short-term temporal associations, suggesting a defect in short-term memory. In addition, they show lowered aggression and altered social behavior. In mice, as in humans, lack of Gdi1 spares most central nervous system functions and preferentially impairs only a few forebrain functions required to form temporal associations. The general similarity to human mental retardation is striking, and suggests that the Gdi1 mutants may provide insights into the human defect and into the molecular mechanisms important for development of cognitive functions.