Summary
Background
Alopecia areata (AA) is a common autoimmune condition, causing inflammation‐induced hair loss. This disease has very limited treatment possibilities, and no treatment is either ...curative or preventive. Platelet‐rich plasma (PRP) has emerged as a new treatment modality in dermatology, and preliminary evidence has suggested that it might have a beneficial role in hair growth.
Objectives
To evaluate the efficacy and safety of PRP for the treatment of AA in a randomized, double‐blind, placebo‐ and active‐controlled, half‐head, parallel‐group study.
Methods
Forty‐five patients with AA were randomized to receive intralesional injections of PRP, triamcinolone acetonide (TrA) or placebo on one half of their scalp. The other half was not treated. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair regrowth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki‐67 evaluation. Patients were followed for 1 year.
Results
PRP was found to increase hair regrowth significantly and to decrease hair dystrophy and burning or itching sensation compared with TrA or placebo. Ki‐67 levels, which served as markers for cell proliferation, were significantly higher with PRP. No side‐effects were noted during treatment.
Conclusions
This pilot study, which is the first to investigate the effects of PRP on AA, suggests that PRP may serve as a safe and effective treatment option in AA, and calls for more extensive controlled studies with this method.
What's already known about this topic?
Platelet‐rich plasma (PRP) has emerged as a new treatment modality in dermatology, and preliminary evidence has suggested that it might have a beneficial role in hair growth.
No study has ever evaluated the effect of PRP on hair growth in patients with alopecia areata (AA).
What does this study add?
PRP was found to increase hair regrowth compared with triamcinolone acetonide or placebo, and Ki‐67 levels were significantly higher. PRP also decreased the percentage of dystrophic hairs and burning or itching sensation.
This study, which is the first to investigate the effects of PRP on AA, suggests that PRP may serve as a safe and effective treatment option in AA.
In endothelial cells, caveolin-1, the structural protein of caveolae, acts as a scaffolding protein to cluster lipids and signaling molecules within caveolae and, in some instances, regulates the ...activity of proteins targeted to caveolae. Specifically, different putative mediators of the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation are located in caveolae and/or regulated by the structural protein caveolin-1, such as potassium channels, calcium regulatory proteins, and connexin 43, a molecular component of gap junctions.
Comparing relaxation in vessels from caveolin-1 knockout mice and their wild-type littermates, we observed a complete absence of EDHF-mediated vasodilation in isolated mesenteric arteries from caveolin-1 knockout mice. The absence of caveolin-1 is associated with an impairment of calcium homeostasis in endothelial cells, notably, a decreased activity of Ca2+-permeable TRPV4 cation channels that participate in nitric oxide- and EDHF-mediated relaxation. Moreover, morphological characterization of caveolin-1 knockout and wild-type arteries showed fewer gap junctions in vessels from knockout animals associated with a lower expression of connexins 37, 40, and 43 and altered myoendothelial communication. Finally, we showed that TRPV4 channels and connexins colocalize with caveolin-1 in the caveolar compartment of the plasma membrane.
We demonstrated that expression of caveolin-1 is required for EDHF-related relaxation by modulating membrane location and activity of TRPV4 channels and connexins, which are both implicated at different steps in the EDHF-signaling pathway.
Summary
Background
Sun exposure is responsible for long‐term clinical skin changes such as photoageing, photodamage and photocancers. Ultraviolet (UV)A wavelengths stimulate the production of ...reactive oxygen species (ROS) that may contribute to photoageing. To protect against oxidative stress, skin cells have developed several defence systems, including ROS and metal ion scavengers and a battery of detoxifying, haem‐degrading and repair enzymes. Melatonin's antioxidant activity is the result of three different but complementary actions: (i) a direct action due to its ability to act as a free radical scavenger; (ii) an indirect action that is a consequence of melatonin's ability to reduce free radical generation (radical avoidance); and (iii) its ability to upregulate antioxidant enzymes.
Objectives
In this study, we focused our attention on the prevention of photodamage, choosing melatonin as an antioxidant agent.
Methods
In the present study we analysed the effects of pretreatment of murine fibroblasts cells (NIH3T3) with melatonin (1 mmol L−1) followed by UVA irradiation (15 J cm−2). Thereafter, changes in components of the extracellular matrix and in some antioxidant enzymes (inducible and constitutive haem oxygenase) were evaluated.
Results
We observed that UVA radiation caused altered expression of extracellular matrix proteins and induced the expression of inducible haem oxygenase. This increase was not sufficient to protect the cells from damage. Instead, melatonin pretreatment led to increased expression of haem‐degrading enzymes and suppression of UVA‐induced photodamage.
Conclusions
These results suggest that melatonin, as a modifier of the dermatoendocrine system, may have utility in reducing the effects of skin ageing.
What's already known about this topic?
Ultraviolet (UV)A radiation is responsible for skin induced‐oxidative stress, photoageing, photodamage and photocancers.
Melatonin might help to maintain a functional epidermal barrier and protect keratinocytes and dermal fibroblasts against the damaging effects of UV radiation.
What does this study add?
Fibroblast haem oxygenase (HO)‐1 is upregulated after a short interval of UVA irradiation.
Melatonin restores the physiological balance between synthesis and degradation of extracellular matrix proteins via the induction of HO‐1 in murine fibroblasts irradiated with UVA.
Abstract Mandibular and maxillary nerve supplies are described in most anatomy textbooks. Nevertheless, several anatomical variations can be found and some of them are clinically relevant. Several ...studies have described the anatomical variations of the branching pattern of the trigeminal nerve in great detail. The aim of this review is to collect data from the literature and gives a detailed description of the innervation of the mandible and maxilla. We carried out a search of studies published in PubMed up to 2011, including clinical, anatomical and radiological studies. This paper gives an overview of the main anatomical variations of the maxillary and mandibular nerve supplies, describing the anatomical variations that should be considered by the clinicians to understand pathological situations better and to avoid complications associated with anaesthesia and surgical procedures.
Highlights • Using a model of neonatal excitotoxic brain injury, we shows an early opening of the BBB that likely contributes to damage. • In this model, we demonstrate that melatonin specifically ...prevents this early BBB alteration. • Our study shows an early BBB disruption in perinatal damage and further extend the neuroprotective profile of melatonin.
Background and Purpose
Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role ...in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain.
Experimental Approach
Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL‐1β and IL‐10 levels, along with glia activation, were evaluated.
Key Results
Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI‐induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR2 were up‐regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury‐induced overexpression of PROK2, significantly blunted nerve injury‐induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti‐inflammatory cytokines in periphery and in spinal cord.
Conclusion and Implications
The prokineticin system contributes to pain modulation via neuron–glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.
The aim of this study was to test the in vitro differentiation effects of concentrated growth factors (CGF), a platelet rich preparation, using SH-SY5Y cells, derived from human neuroblastoma.
...SH-SY5Y cells were cultured in presence of CGF or retinoic acid (RA). After 72 h of treatment, different parameters were investigated: cell proliferation by an automated cell counter; cell viability by thiazolyl blue tetrazolium bromide (MTT) assay; cell differentiation markers, i.e., neuronal nuclear antigen (NeuN), synaptophysin (SYP) and β3-tubulin, by immunocytochemistry and Western blotting techniques; release of nerve growth factor (NGF) and brain-derived growth factor (BDNF) by enzyme-linked immunosorbent assay (ELISA) and neurite outgrowth by a dedicated image software.
In presence of CGF, the cell proliferation rate and viability decreased, as expected for differentiated SH-SY5Y cells. On the contrary, the cellular differentiation markers increased their expression together with the release of growth factors. Moreover, the neurite outgrowth was improved.
The data suggest that CGF treatment positively affects the cell differentiation, regulating the expression of neuronal markers, the release of growth factors and the neurite length. Taken together these results seem to be promising in the development of new approaches for neural regeneration.
: Tobacco smoking is responsible for death of many people each year and increases the risk of developing numerous disorders, particularly cardiovascular disease and cancer. Among the components of ...cigarette smoke, nicotine is known to excert proatherosclerotic, prothrombotic and proangiogenic effects on vascular endothelial cells. The current study was designed to investigate the mechanisms by which nicotine induces endothelial dysfunction and further to examine whether melatonin protects against nicotine‐induced vasculopathy. Four groups of male rats (controls, melatonin‐treated, nicotine treated 100 μg/mL in drinking water, and nicotine plus melatonin 5 mg/kg/day treated) were used in this study. After 28 days all the animals were killed by decapitation and the aorta was removed. We evaluated the hydroxyproline content, and the different expression of proteins involved in several types of stress (ERK1/2), in fibrosis (TGF‐β1, NF‐κB) and in recruitment of circulating leukocytes onto the vessel wall, including intercellular adhesion molecule‐1 (ICAM‐1) and vascular cellular adhesion molecule‐1 (VCAM‐1). These metabolic pathways are important in the development of nicotine‐induced atherosclerosis and hypertension. Our results show that nicotine induces marked structural and functional alterations in the aorta. Nicotine receptor binding results in activation and phosphorylation of ERK 1/2. This enzyme, in turn, activates both TGF‐β1 and NF‐κB; they stimulate respectively the synthesis of type I collagen, responsible of fibrosis, and moreover ICAM‐1, VCAM‐1 and reactive oxygen species. Based on these findings, melatonin is able to minimize the negative effects of nicotine by blocking the activation of ERK and the other signalling pathways in which this enzyme is involved.
Re-usable air/water and suction valves used in endoscopes often demonstrate risk of infection. To the authors' knowledge, the safety and efficacy of re-usable and single-use valves have not been ...compared to date. As such, a laboratory investigation was undertaken to compare the safety and efficacy of re-usable and single-use valves at 11 Italian endoscopy sites. Safety was evaluated by analysing the rinse liquid of reprocessed re-usable valves ready for use, and efficacy was assessed based on the completion of endoscopic procedures without valve malfunction. This study found significantly lower contamination of single-use valves compared with re-usable valves (0 vs 29.1%, respectively; P=0.007) and similar efficacy (97.6 vs 98.8%, respectively; P=ns). Microbiological analysis of the rinse liquid of reprocessed re-usable valves identified various surviving micro-organisms and highlighted their potential pathogenicity. Such data suggest that sterile single-use valves may be safer than re-usable valves, and have comparable performance.
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