Solar Lentigines: Evaluating Pulsed Dye Laser (PDL) as an Effective Treatment Option

INTRODUCTION: Solar lentigines are among commonest cosmetic problems. There are many topical therapies suggested to treat these lesions including cryotherapy, chemical peeling with tri chloro acetic acid (TCA) and laser therapy with q-switched lasers as well as long pulsed lasers. Considering possible treatment side effects (PIH, scar) with cryotherapy and peeling in Iranian patients (darker skin types) it seems necessary to try to find alternative measures. The aim of the present study was to evaluate effect of long pulsed dye laser (LPDL) on lentigines via an objective method (computerized dermoscopy).METHODS: Patients with pathologically confirmed lentigines were selected if they agreed to participate in the study,were not treated before, hadn’t history of psoriasis, vitiligo, scar formation and were not pregnant. Letigines were dermoscopied before and after treatment with PDL (V-beam, 595nm, Candela Corp. Wayland, USA) using fluence of 10 joules, without DCD (dynamic cooling device) via extra compress lens provided with laser system. The resulting figures were compared by two academic unrelated dermatologists as well as by computerized analysis. Post laser side effects were treated with topical antibiotics and mild topical steroids. Patients were followed for six months after the end of the study to determine the rate of recurrence via dermoscopy of sites of previous lesions and also delayed side effects.RESULTS: A total of 21 patients with the same number of lesions, were included in the study. Mean age of patients was 54.2 years (±23.3) ranging from 39 to 71 years. Included patients were 18 females and three males. From 21 treated lesions, 11 were located on the hands and 10 on the face. Comparing before and after photographs taken through dermoscopy system, revealed that approximately 57% of patients had more than 75% improvement. Mean pigment analysis score (calculated by computerized dermoscope software) was respectively 8 and 2 before and after PDL therapy, showing noticeable decrease in pigment density of lesions. Side effects were mild erythema and local irritation responding to topical mild steroids. No hypo or persistent hyper pigmentation or other delayed side effects was seen after six months follow up. One patient experienced transient hyper pigmentation of treatment site after treatment. During six months follow up, no recurrences were seen.CONCLUSION: In conclusion, PDL is a safe and effective option to treat lentigines if applied properly using compression method, especially in Iranian patients. However, further studies with larger sample size are required to confirm these results

Social Networking of Group Two Innate Lymphoid Cells in Allergy and Asthma

Allergic diseases including asthma, chronic rhinosinusitis, and atopic dermatitis are common conditions worldwide. While type 2 immune responses induced by T-cells significantly cause allergic inflammation, the recently identified group two innate lymphoid cells (ILC2s) are emerging as critical players in the development of allergy. Upon allergen exposure, ILC2s are rapidly activated by cytokines released by epithelial cells. Activated ILC2s release various effector cytokines altogether contributing to the pathogenesis of allergy and can even cause inflammation in the absence of T-cells, as observed in asthma. Although the factors inducing ILC2 activation have been identified, evidence suggests that multiple factors can enhance or repress ILC2 proliferation, trafficking, or secretion of effector cytokines upon allergic inflammation. In this review, we discuss the recent findings that influence ILC2 activation and the resulting effects on the pathogenesis of allergy. A better understanding of how ILC2s are modulated will open the door to the development of new therapeutic strategies against allergic diseases

Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E)18.5 and adult mice revealed shortened anogenital distance (AGD), open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans

Inclusion of CD80 in HSV Targets the Recombinant Virus to PD-L1 on DCs and Allows Productive Infection and Robust Immune Responses

CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC

Bioengineering Human Scaffold-free Cartilage Constructs Using Paediatric Auricular Tissue

Currently, patients with external ear deformities rely on hyaline cartilage grafts or silicone prosthesis to provide them with adequate external ear reconstruction. Scaffold-free auricular tissue engineering provides a means of creating patient specific cartilage constructs solely using their own cells, ensuring biocompatibility, long term stability, and reduced morbidity. Here, we have developed a simple method for generating scaffold-free auricular constructs using paediatric auricular cartilage remnants. High cell density micromass cultures treated with chondrogenic medium for prolonged periods result in mechanically stable cartilage constructs resembling native paediatric auricular cartilage mechanically, histologically, immunohistochemically, and biochemically.M.Sc

Conventional Vs. reverse nerve grafting for peripheral nerve repair in lower extremity of rats

Background: Autograft is the best option in nerve defects when end-to-end repair can not sufficiently preserve nerve continuity. Theoretically, if the severed nerve is reversely grafted, it may prevent axonal growth into nerve branches, and larger amounts of axons will reach the target organ and more satisfactory results will be obtained. In this study we aimed to compare conventional versus reverse nerve grafting.Methods: This study was performed in Animal laboratory of Hazrat Fatemeh Hospital from April till August 2011. We randomly divided 40 Wistar rats into two groups. We excised 1.5 cm of the right sciatic nerve and anastomosed it conventionally between the proximal and distal ends of the nerve in rats in group A and in a reverse manner in rats in group B. The rats’ footprints were recorded in the first and 16th weeks after surgery. In week 16, the grafted nerves were removed under anesthesia for pathological examination and axon count. Subsequently, the results were compared clinically by sciatic functional index (SFI) through footprint analysis and paraclinically by axon count. A p-value smaller than 0.05 was considered statistically significant.Results: Conventional and reverse nerve grafting no had statistically significant differences in clinical assessment in the first and 16th weeks (P=0.87) post-surgically and also no difference in paraclinical assessment in week 16 (P=0.68). Conclusion: We had no significant clinically or para clinically differences between two approaches. It should be considered that the diameter and length of nerves and muscles in human is larger than rats, so the results of nerve repair may differ in human. We suggest a study in animal model which is anatomically more similar to human

Adult Gli2+/-;Gli3Δ699/+ Male and Female Mice Display a Spectrum of Genital Malformation.

Disorders of sexual development (DSD) encompass a broad spectrum of urogenital malformations and are amongst the most common congenital birth defects. Although key genetic factors such as the hedgehog (Hh) family have been identified, a unifying postnatally viable model displaying the spectrum of male and female urogenital malformations has not yet been reported. Since human cases are diagnosed and treated at various stages postnatally, equivalent mouse models enabling analysis at similar stages are of significant interest. Additionally, all non-Hh based genetic models investigating DSD display normal females, leaving female urogenital development largely unknown. Here, we generated compound mutant mice, Gli2+/-;Gli3Δ699/+, which exhibit a spectrum of urogenital malformations in both males and females upon birth, and also carried them well into adulthood. Analysis of embryonic day (E)18.5 and adult mice revealed shortened anogenital distance (AGD), open ventral urethral groove, incomplete fusion of scrotal sac, abnormal penile size and structure, and incomplete testicular descent with hypoplasia in male mice, whereas female mutant mice displayed reduced AGD, urinary incontinence, and a number of uterine anomalies such as vaginal duplication. Male and female fertility was also investigated via breeding cages, and it was identified that male mice were infertile while females were unable to deliver despite becoming impregnated. We propose that Gli2+/-;Gli3Δ699/+ mice can serve as a genetic mouse model for common DSD such as cryptorchidism, hypospadias, and incomplete fusion of the scrotal sac in males, and a spectrum of uterine and vaginal abnormalities along with urinary incontinence in females, which could prove essential in revealing new insights into their equivalent diseases in humans

Orai inhibition modulates pulmonary ILC2 metabolism and alleviates airway hyperreactivity in murine and humanized models.

Ca2+ entry via Ca2+ release-activated Ca2+ (CRAC) channels is a predominant mechanism of intracellular Ca2+ elevation in immune cells. Here we show the immunoregulatory role of CRAC channel components Orai1 and Orai2 in Group 2 innate lymphoid cells (ILC2s), that play crucial roles in the induction of type 2 inflammation. We find that blocking or genetic ablation of Orai1 and Orai2 downregulates ILC2 effector function and cytokine production, consequently ameliorating the development of ILC2-mediated airway inflammation in multiple murine models. Mechanistically, ILC2 metabolic and mitochondrial homeostasis are inhibited and lead to the upregulation of reactive oxygen species production. We confirm our findings in human ILC2s, as blocking Orai1 and Orai2 prevents the development of airway hyperreactivity in humanized mice. Our findings have a broad impact on the basic understanding of Ca2+ signaling in ILC2 biology, providing potential insights into the development of therapies for the treatment of allergic and atopic inflammatory diseases