Upregulation of the Axonal Growth and the Expression of Substance P and its NK1 Receptor in Human Allergic Contact Dermatitis

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.     

Neuronal changes in psoriasis exacerbation

Background The nervous system contributes to inflammatory skin diseases.
Objective The aim of this investigation was to study the neuronal contribution to psoriasis at the remission and exacerbation phases.
Methods We examined the expression of the neuronal markers protein gene product 9.5 (PGP 9.5), growth-associated protein-43 (GAP-43) and substance P, in addition to its receptor (R), neurokinin-1R (NK-1R) in psoriatic skin from seven female patients at remission and exacerbation, using immunohistochemistry.
Results The number of epidermal PGP 9.5 immunoreactive nerve fibres in the involved skin during exacerbation was decreased ( P  < 0.01) compared to involved skin at remission and non-involved skin at the exacerbation phase. GAP-43-positive nerve fibres were decreased ( P  < 0.05) in the involved skin in contrast to non-involved skin, during exacerbation. Substance P expression was seen on both immunoreactive nerve fibres and cells with a down-regulation ( P  < 0.01) in the number of positive nerve fibres in the involved skin compared to non-involved skin, at the exacerbation phase. The number of substance P-positive cells was slightly lower in the involved skin at exacerbation than at remission. The number of NK-1R immunoreactive cells was increased ( P  < 0.01) in the involved skin in contrast to non-involved skin, at the exacerbation phase.
Conclusion Our findings suggest a crosstalk between the nervous system and inflammation during psoriasis exacerbation in the form of an altered expression of nerve fibres, substance P and its NK-1R.     

Survey of Pest Infestation, Asthma, and Allergy in Low-income Housing

Low-income housing often has multiple indoor health risks. Among them, pest infestation, pesticide use, and pest allergens are recognized as common risks which affect residents’ health. Cockroach and rodent allergens are associated with morbidity and mortality of asthmatics. To characterize the levels of pest infestation, residents’ attitudes toward pest control, and the relationships among cockroaches, mice, cockroach allergen level, asthma and allergy rate in public housing, we interviewed residents from 358 randomly selected apartments in Gary, Indiana and assessed the environmental conditions. Dust samples were collected from 101 apartment kitchen floors to analyze for cockroach allergen (Bla g 1 and Bla g 2) levels. Eighty one percent of the apartments were found infested by cockroaches, mice, ants, spiders, or flies. In the 101 apartments evaluated, 98% of the kitchen dust samples had detectable levels of Bla g 1 allergen (≥0.4 U/g), 52% had ≥2 U/g, and 33% had ≥8 U/g of Bla g 1. Among the 1,173 residents, 13% and 9% had physician-diagnosed asthma and allergy, respectively. Existence of diagnosed asthmatic was positively correlated with mouse infestations.     

Chronic mild stress modulates 5-HT1A and 5-HT2A receptor expression in the cerebellar cortex of NC/Nga atopic-like mice

Atopic eczema symptoms may worsen due to stress. In the present study, the cerebellar cortex of the atopic-like mouse NC/Nga was studied regarding the effect of chronic mild stress on expression of two well-characterized serotonergic receptors (R), 5-HT1A and 5-HT2A. In total 24 mice were used. Sixteen of these mice were subjected to unpredictable stressors for 12 weeks, and 8 mice were used as controls. In order to evoke an eczema, a mite antigen was applied to 16 mice from week 9 of the experiment. Thus, three groups of mice, stressed eczematous (SE), non-stressed eczematous (NSE) and stressed control (SC), respectively, were obtained. The expression of the 5-HT1AR was analyzed using quantitative immunohistochemistry. For evaluation of 5-HT2AR a semi-quantitative technique was used, the cell density and signal intensity being measured. The highest average value for 5-HT1AR expression, in the Purkinje cells, was recorded in the NSE group, while the lowest average was in the SC group. 5-HT1AR expression differed significantly between the groups. The highest average value for density of 5-HT2AR positive Purkinje cells was evident in the SE group, while the lowest was in the SC group, this difference between groups also being statistically significant. In addition, the signal intensity was highest in the SE group, with a difference compared to the other groups. In conclusion, chronic mild stress modulates serotonergic receptor expressions in the cerebellar cortex of atopic-like mice.     

Serotonin transporter protein overexpression and association to Th 17 and T regulatory cells in lupoid leishmaniasis

The immunopathogenesis of chronic non-healing Old World cutaneous leishmaniasis is challenging. There is a bidirectional communication between the nervous and immune systems, serotonin being an important mediator in this respect. Our aim was to study the role of the serotonin transporter protein (SERT) and its relation to T cell-related immune responses in lupoid leishmaniasis. Paraffin-embedded skin biopsies of 12 cases of lupoid and 12 cases of usual types of cutaneous leishmaniasis were investigated using immunohistochemistry regarding expression of SERT, Th1, Th2, Th17 and T regulatory cell (Treg) markers. SERT as well as Tregs and interleukin (IL)-17 positive cells were more prevalent while IL-5 (Th2) and interferon (IFN)-γ (Th1) expressing cells were less numerous in the lupoid tissue compared to those from the usual type of leishmaniasis. The majority of the SERT⁺ cells were also tryptase⁺ (mast cells). There was a positive correlation between a higher number of SERT⁺ and IL-17⁺ cells in the lupoid type, while lower numbers of SERT⁺ cells were significantly related to lower percentages of CD25⁺ cells in the usual type of leishmaniasis. These results might indicate a role for SERT, Th17 and Tregs in the pathogenesis of lupoid leishmaniasis.     

Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.     

Effects of the hypo-osmotic swelling test on the outcome of intracytoplasmic sperm injection for patients with only nonmotile spermatozoa available for injection: a prospective randomized trial

OBJECTIVE: Hypo-osmotic swelling test (HOST) has been shown to be an effective method for the selection of live sperm. On-going pregnancies were obtained by using HOST-selected sperm. The aim of this study was to evaluate the effect of using HOST-selected "live" sperm versus nonselected sperm on the outcome of intracytoplasmic sperm injection cycles when only nonmotile sperm were available for injection. DESIGN: Prospective randomized study. SETTING: Governmental tertiary care hospital. PATIENT(S): Thirty ICSI cycles with no motile sperm were included in this study. INTERVENTION(S): For the HOST group, potentially live spermatozoa detected by hypo-osmotic reaction of the tail were injected into oocytes. For the No-HOST group, the sperm were randomly injected into the oocytes without checking the viability. MAIN OUTCOME MEASURE(S): The fertilization, cleavage, embryo quality, pregnancy, and implantation rates were assessed for the two groups. RESULT(S): Among 30 cycles, 15 fall into each group. Fertilization, cleavage rates, and the number of good quality embryos were similar between two groups. CONCLUSION(S): HOST-selected live spermatozoa can be safely used for intracytoplasmic sperm injection to establish pregnancies. There is a tendency for higher pregnancy and implantation rates to result, but it does not reach statistical significance.     

Childhood systemic lupus erythematosus in Sultanate of Oman: demographics and clinical analysis

There is a worldwide variation in the incidence of childhood manifestation of systemic lupus erythematosus, which may be related to environmental, genetic and geographical factors. The aim of the study is to describe for the first time the clinical and immunological characteristics of childhood onset systemic lupus erythematosus at diagnosis in the Sultanate of Oman. We retrospectively reviewed the records of 50 children with systemic lupus erythematosus fulfilling the American College of Rheumatology criteria between 1990 and 2006. There were 42 girls and eight boys. The mean age of disease onset was low at 8.6 years (SD 3.1). The female:male ratio was 5.3:1. The most frequent clinical manifestations at initial diagnosis were: articular (76%), cutaneous (70%), haematological (68%) and renal (64%) dominated by class IV nephritis, pulmonary (26%), neuropsychiatric (18%) and cardiac (10%). A positive antinuclear antibody (>1:80) was present in 94% at diagnosis. Positive anti-double stranded DNA was present in 82% and low complement levels were present in 84% at diagnosis. This is the first review of childhood onset systemic lupus erythematosus in the Sultanate of Oman.     

GABA and GABAA receptor expression on immune cells in psoriasis: a pathophysiological role

Psoriasis is a chronic inflammatory disease in which pruritus is a common symptom. Pruritus may be associated with the gamma-aminobutyric acid (GABA) system. The distribution of GABA and its GABA_A receptor (R) was studied in involved and non-involved psoriatic skin, as well as normal healthy control skin, using an immunohistochemistry technique. Pruritus was determined using a visual analog scale. Inflammatory cells immunoreactive for the GABA ligand and the GABA_A R were increased (P < 0.01, respectively) in the involved skin. Cells stained for GABA ligand were mostly macrophages with some lymphocytes, while cells stained for GABA_A R were macrophages, neutrophils or lymphocytes. There was a positive correlation when comparing GABA ligand (P = 0.05) and GABA_A R (P < 0.05) expressing inflammatory cells, with pruritus. The GABA ligand and its GABA_A R may play a role for the pathogenesis of psoriasis as well as for pruritus in this disease.     

Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress

Objective To identify pathoaetiological neuroimmune mechanisms in patients with atopic dermatitis (AD) and chronic stress, focusing at nerve density, sensory neuropeptides, and the serotonergic system. Methods Eleven patients with AD with histories of stress worsening were included. Biopsies from involved and non‐involved skin were processed for immunohistochemistry. Salivary cortisol test was done as a marker for chronic stress. Results There were more acanthosis and fewer nerve fibres in epidermis and papillary dermis of involved compared with non‐involved skin. Whereas there was no significant change in the number of substance P and calcitonin gene‐related peptide–positive nerve fibres between the involved and non‐involved skin, there was an increase in the epidermal fraction of 5‐hydroxtrytamine 1A (5‐HT1A) receptor and serotonin transporter protein (SERT) immunoreactivity in the involved skin. The number of 5‐HT2AR, CD3‐positive cells, and SERT‐positive cells, most of them being CD3 positive, was increased in involved skin. There was an increase in mast cells in the involved skin, and these cells were often located close to the basement membrane. There was a strong tendency to a correlation between 5‐HT2AR positive cells in the papillary dermis of involved skin and low cortisol ratios, being an indicator of chronic stress. Conclusion A changed innervation and modulation of the serotonergic system are indicated in chronic atopic eczema also during chronic stress.