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1.
Dermatol Ther (Heidelb) ; 14(2): 391-408, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38175365

RESUMEN

INTRODUCTION: The skin of patients with atopic dermatitis (AD) is characterised by elevated pH. As a central homeostatic regulator, an increased pH accelerates desquamation and suppresses lipid processing, resulting in diminished skin barrier function. The aim of this study was to determine whether a novel zinc lactobionate emollient cream can strengthen the skin barrier by lowering skin surface pH. METHODS: A double-blind, forearm-controlled cohort study was undertaken in patients with AD. Participants applied the test cream to one forearm and a vehicle cream to the other (randomised allocation) twice daily for 56 days. Skin surface pH and barrier function (primary outcomes) were assessed at baseline and after 28 days and 56 days of treatment, amongst other tests. RESULTS: A total of 23 adults with AD completed the study. During and after treatment, a sustained difference in skin surface pH was observed between areas treated with the test cream and vehicle (4.50 ± 0.38 versus 5.25 ± 0.54, respectively, p < 0.0001). This was associated with significantly reduced transepidermal water loss (TEWL) on the test cream treated areas compared with control (9.71 ± 2.47 versus 11.20 ± 3.62 g/m2/h, p = 0.0005). Improvements in skin barrier integrity, skin sensitivity to sodium lauryl sulphate, skin hydration, and chymotrypsin-like protease activity were all observed at sites treated with the test cream compared with the control. CONCLUSION: Maintenance of an acidic skin surface pH and delivery of physiologic lipids are beneficial for skin health and may help improve AD control by reducing sensitivity to irritants and allergens.

2.
J Allergy Clin Immunol ; 153(3): 732-741.e8, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37926123

RESUMEN

BACKGROUND: A diagnosis of atopic dermatitis (AD) is common during infancy; however, it is unclear whether differential skin barrier development defines this period and signals disease onset in predisposed individuals. OBJECTIVE: We sought to study (NCT03143504) and assess the feasibility of remote skin testing from birth to monitor skin barrier maturation and model association with an AD diagnosis by age 12 months. METHODS: Biophysical testing and infrared spectroscopy were conducted at the maternity ward and family home. Tape stripping collected samples for desquamatory protease and natural moisturizing factor analysis. The 4 common European filaggrin risk alleles were screened. RESULTS: A total of 128 infants completed the study, with 20% developing mild disease. Significant changes in permeability barrier function, desquamatory protease activity, and molecular composition assessed spectroscopically were observed longitudinally, but only subtle evidence of differential skin barrier development was noted between infant subgroups. Common filaggrin risk alleles were strongly associated with early-onset disease and conferred a significant reduction in natural moisturizing factor and water content by age 4 weeks. Accounting for a family history of atopy, these parameters alongside a greater lipid/protein ratio and reduced chymotrypsin-like activity at birth were associated with AD. Measured in ambient conditions, transepidermal water loss did not signal disease risk at any stage. CONCLUSIONS: Skin barrier dysfunction lacked an acquired modality but was considered proportional to cohort severity and suggests that a portfolio of tests used in a community setting has the potential to improve current AD risk evaluations from birth.


Asunto(s)
Dermatitis Atópica , Lactante , Recién Nacido , Humanos , Femenino , Embarazo , Dermatitis Atópica/diagnóstico , Estudios de Cohortes , Proteínas Filagrina , Agua , Susceptibilidad a Enfermedades , Péptido Hidrolasas , Piel
3.
Clin Exp Dermatol ; 47(6): 1154-1164, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35167133

RESUMEN

BACKGROUND: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no-treatment control. AIM: To compare the barrier-strengthening properties of a new moisturizer containing urea and glycerol (urea-glycerol cream; UGC), with those of a glycerol-containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no-treatment control (NTC). METHODS: This was an observer-blinded prospective Phase 2 within-subject multilateral single-centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier. RESULTS: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (-9.0 g/m2 /h; 95% CI -12.56 to -5.49), with PC (-9.0 g/m2 /h; 95% CI -12.60 to -5.44) and with GC -4.2 g/m2 /h; 95% CI 7.76 to -0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG-dependent enhancement of treatment effects. CONCLUSION: The study showed that not all emollient creams for eczema are equal. The simple paraffin-based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS-induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long-term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema.


Asunto(s)
Dermatitis Atópica , Eccema , Adulto , Niño , Dermatitis Atópica/tratamiento farmacológico , Eccema/tratamiento farmacológico , Emolientes/uso terapéutico , Glicerol , Humanos , Irritantes , Parafina/farmacología , Parafina/uso terapéutico , Estudios Prospectivos , Prurito/tratamiento farmacológico , Crema para la Piel/uso terapéutico , Urea/uso terapéutico , Pérdida Insensible de Agua
4.
Br J Dermatol ; 186(5): 875-886, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34921679

RESUMEN

BACKGROUND: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. OBJECTIVES: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. METHODS: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface. RESULTS: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m-2 h-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness. CONCLUSIONS: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.


Asunto(s)
Eccema , Anomalías Cutáneas , Adulto , Eccema/tratamiento farmacológico , Eccema/prevención & control , Emolientes/uso terapéutico , Humanos , Piel , Anomalías Cutáneas/tratamiento farmacológico , Dodecil Sulfato de Sodio/farmacología , Agua , Pérdida Insensible de Agua
6.
Inflamm Res ; 69(10): 1015-1017, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32780184

RESUMEN

The 49th annual meeting of the European Histamine Research Society (EHRS) was planned to be held at 'Die Wolfsburg', Mühlheim an der Ruhr near Düsseldorf in Germany. With the announcement of the COVID-19 pandemic, the face-to-face conference meeting was cancelled and instead, the EHRS Council proposed an Online Symposium to keep up the good spirits and research enthusiasm of the Society members. This meeting report summarises two 2 h sessions held on 1st and 2nd July, 2020 and delivered via Blackboard Collaborate. The Online Symposium covered a range of interesting and inspiring topics around the molecular and clinical pharmacology of histamine, with nine exciting presentations delivered by young and senior members of the Society across both days.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , COVID-19 , Humanos , Pandemias , SARS-CoV-2
7.
Dermatol Ther (Heidelb) ; 10(5): 1031-1041, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32671664

RESUMEN

INTRODUCTION: The replenishment of skin lipids depleted in the dry skin state is a desirable therapeutic target to restore skin moisturization; however, there is limited evidence demonstrating the success of this approach through the use of topical emollients. The purpose of this study was to provide evidence of the benefits of a cream and equivalent lotion containing skin lipids in a multi-vesicular emulsion for the management of dry skin. The hypothesis was that the test cream and test lotion could sustain skin moisturization for longer than traditional emollients by sustainably delivering skin lipids. METHODS: A double-blind intra-subject vehicle-controlled single open-application test on the lower legs in people with dry, atopic dermatitis (atopic eczema)-prone, skin was conducted. There were six treatment sites, three per lower leg in each participant, which were treated with the test cream, the test lotion, three reference creams commonly prescribed in the UK and no treatment as a control. After baseline measurements of skin hydration, 100 µl of the test/reference creams was applied to each of the relevant treatment sites (random site allocation). Following treatment, measurements of skin hydration and scoring of visual dryness was conducted at timed intervals (3, 6, 12 and 24 h post-product application). RESULTS: The test cream and lotion both significantly increased skin hydration and reduced skin dryness for at least 24 h following a single application compared to a no treatment control site. Compared to three reference emollient creams the test cream and test lotion were the only products capable of sustaining clinically meaningful improvements in skin moisturization for 24 h. CONCLUSION: The sustained moisturization imparted by the test products reduces the need for frequent emollient application, often requiring 3-4 applications per day for traditional emollients, and should reduce the high burden of managing dry skin conditions like atopic dermatitis.

8.
J Clin Endocrinol Metab ; 104(4): 1187-1199, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30252067

RESUMEN

CONTEXT: Hypoglycemia is emerging as a risk for cardiovascular events in diabetes. We hypothesized that hypoglycemia activates the innate immune system, which is known to increase cardiovascular risk. OBJECTIVE: To determine whether hypoglycemia modifies subsequent innate immune system responses. DESIGN AND SETTING: Single-blinded, prospective study of three independent parallel groups. PARTICIPANTS AND INTERVENTIONS: Twenty-four healthy participants underwent either a hyperinsulinemic-hypoglycemic (2.5 mmol/L), euglycemic (6.0 mmol/L), or sham-saline clamp (n = 8 for each group). After 48 hours, all participants received low-dose (0.3 ng/kg) intravenous endotoxin. MAIN OUTCOME MEASURES: We studied in-vivo monocyte mobilization and monocyte-platelet interactions. RESULTS: Hypoglycemia increased total leukocytes (9.98 ± 1.14 × 109/L vs euglycemia 4.38 ± 0.53 × 109/L, P < 0.001; vs sham-saline 4.76 ± 0.36 × 109/L, P < 0.001) (mean ± SEM), mobilized proinflammatory intermediate monocytes (42.20 ± 7.52/µL vs euglycemia 20.66 ± 3.43/µL, P < 0.01; vs sham-saline 26.20 ± 3.86/µL, P < 0.05), and nonclassic monocytes (36.16 ± 4.66/µL vs euglycemia 12.72 ± 2.42/µL, P < 0.001; vs sham-saline 19.05 ± 3.81/µL, P < 0.001). Following hypoglycemia vs euglycemia, platelet aggregation to agonist (area under the curve) increased (73.87 ± 7.30 vs 52.50 ± 4.04, P < 0.05) and formation of monocyte-platelet aggregates increased (96.05 ± 14.51/µL vs 49.32 ± 6.41/µL, P < 0.05). Within monocyte subsets, hypoglycemia increased aggregation of intermediate monocytes (10.51 ± 1.42/µL vs euglycemia 4.19 ± 1.08/µL, P < 0.05; vs sham-saline 3.81± 1.42/µL, P < 0.05) and nonclassic monocytes (9.53 ± 1.08/µL vs euglycemia 2.86 ± 0.72/µL, P < 0.01; vs sham-saline 3.08 ± 1.01/µL, P < 0.05), with platelets compared with controls. Hypoglycemia led to greater leukocyte mobilization in response to subsequent low-dose endotoxin challenge (10.96 ± 0.97 vs euglycemia 8.21 ± 0.85 × 109/L, P < 0.05). CONCLUSIONS: Hypoglycemia mobilizes monocytes, increases platelet reactivity, promotes interaction between platelets and proinflammatory monocytes, and potentiates the subsequent immune response to endotoxin. These changes may contribute to increased cardiovascular risk observed in people with diabetes.


Asunto(s)
Endotoxemia/inmunología , Técnica de Clampeo de la Glucosa , Hipoglucemia/inmunología , Inmunidad Innata , Lipopolisacáridos/inmunología , Adulto , Relación Dosis-Respuesta Inmunológica , Endotoxemia/sangre , Endotoxemia/inducido químicamente , Escherichia coli , Femenino , Glucosa/administración & dosificación , Voluntarios Sanos , Experimentación Humana , Humanos , Hiperglucemia/sangre , Hiperglucemia/inducido químicamente , Hiperglucemia/inmunología , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Inyecciones Intravenosas , Insulina/administración & dosificación , Lipopolisacáridos/administración & dosificación , Masculino , Monocitos/inmunología , Agregación Plaquetaria/inmunología , Estudios Prospectivos , Adulto Joven
9.
Eur J Pharmacol ; 837: 38-44, 2018 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-30148998

RESUMEN

The diverse effects of histamine are mediated by discrete histamine receptors. The principal repository of histamine in the body is the mast cell. However, the effects of histamine on mast cells, especially those of human origin, have not been fully elucidated. In this study, the expression of histamine receptors in human lung mast cells was evaluated. Moreover, the effects of histamine receptor engagement on both mediator release and chemotaxis were investigated. Mast cells were isolated and purified from human lung tissue. Histamine receptor expression was determined by RT-PCR and q-PCR. Both methods for the detection of histamine receptors were in accordance and human lung mast cells expressed mRNA for histamine H4 and histamine H1 receptors, variably expressed histamine H2 receptor but did not express histamine H3 receptor. The effects of selective histamine receptor agonists on the release of both pre-formed (histamine) and newly-synthesised (cysteinyl-leukotriene, prostaglandin D2) mediators were investigated. None of the agonists tested had any direct effects on mediator release. None of the agonists modulated release stimulated by anti-IgE. Further studies showed that histamine induced migration of mast cells. Chemotaxis appeared to be mediated by the histamine H4 receptor since JNJ28610244 (H4 agonist) was chemotactic for mast cells whereas 2-(2-pyridyl) ethylamine (H1 agonist) was not. Furthermore, the selective histamine H4 receptor antagonist, JNJ7777120, effectively reversed the chemotaxis of mast cells induced by JNJ28610244. Overall, these experiments identify the histamine H4 receptor as chemotactic for human lung mast cells. This mechanism might influence mast cell accumulation in the lung.


Asunto(s)
Quimiotaxis , Pulmón/citología , Mastocitos/fisiología , Receptores Histamínicos H4/fisiología , Humanos , Indoles/farmacología , Pulmón/fisiología , Oximas/farmacología , Piperazinas/farmacología , Receptores Histamínicos H4/agonistas , Receptores Histamínicos H4/análisis
10.
Eur J Pharmacol ; 819: 225-232, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29225187

RESUMEN

Mast cells are an exceptionally rich source of prostaglandin D2 (PGD2). PGD2 is pro-inflammatory and can cause bronchoconstriction. The enzyme cyclooxygenase (COX) is central to the generation of prostanoids such as PGD2. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX. COX exists as two isoforms, COX-1 and COX-2. The principal aim of this study was to establish whether COX-1 and/or COX-2 mediates PGD2 generation from human lung mast cells. Mast cells were isolated from human lung tissue and purified by flotation over Percoll and immunomagnetic bead separations. The cells were activated with anti-IgE or Stem Cell Factor (SCF). The generation of PGD2 was determined by ELISA. The effects of NSAIDs (aspirin, ibuprofen, diclofenac, naproxen, indomethacin), COX-1 selective (FR122047), and COX-2 selective (celecoxib) inhibitors on PGD2 generation were determined. The expression of COX-1 and COX-2 in mast cells was determined by Western blotting. All the NSAIDs tested abrogated stimulated PGD2 generation from mast cells except aspirin which was only weakly effective. FR122047 was an effective inhibitor of PGD2 generation (EC50 ~25nM) from mast cells whereas celecoxib was ineffective. Immunoblotting indicated that COX-1 was strongly expressed in all mast cell preparations while COX-2 expression was weak. No induction of COX-2 was observed following activation of mast cells. These findings indicate that COX-1 is the principal isoform involved in generating PGD2 from human lung mast cells. These studies provide insight into the potential behaviour of NSAIDs in the context of respiratory diseases.


Asunto(s)
Biocatálisis , Ciclooxigenasa 1/metabolismo , Pulmón/inmunología , Mastocitos/metabolismo , Prostaglandina D2/biosíntesis , Ciclooxigenasa 1/genética , Inhibidores de la Ciclooxigenasa/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Mastocitos/citología , Mastocitos/efectos de los fármacos , Mastocitos/enzimología
11.
Br J Pharmacol ; 173(21): 3099-3109, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27460634

RESUMEN

BACKGROUND AND PURPOSE: PGE2 inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE2 has not been defined. The aim of this study was to identify the EP receptor by which PGE2 inhibits cytokine generation from human lung macrophages. This was determined by using recently developed EP receptor ligands. EXPERIMENTAL APPROACH: The effects of PGE2 and EP-selective agonists on LPS-induced generation of TNF-α and IL-6 from macrophages were evaluated. The effects of EP2 -selective (PF-04852946, PF-04418948) and EP4 -selective (L-161,982, CJ-042794) receptor antagonists on PGE2 responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR. KEY RESULTS: PGE2 inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP2 and EP4 receptors. L-902,688 (EP4 receptor-selective agonist) was considerably more potent than butaprost (EP2 receptor-selective agonist) as an inhibitor of TNF-α generation from macrophages. EP2 receptor-selective antagonists had marginal effects on the PGE2 inhibition of TNF-α generation, whereas EP4 receptor-selective antagonists caused rightward shifts in the PGE2 concentration-response curves. CONCLUSIONS AND IMPLICATIONS: These studies demonstrate that the EP4 receptor is the principal receptor that mediates the anti-inflammatory effects of PGE2 on human lung macrophages. This suggests that EP4 receptor agonists could be effective anti-inflammatory agents in human lung disease.


Asunto(s)
Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Dinoprostona/farmacología , Macrófagos Alveolares/efectos de los fármacos , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Antibacterianos/química , Antiinflamatorios no Esteroideos/química , Dinoprostona/química , Humanos , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/microbiología , Pruebas de Sensibilidad Microbiana , Subtipo EP4 de Receptores de Prostaglandina E/antagonistas & inhibidores , Subtipo EP4 de Receptores de Prostaglandina E/genética , Streptococcus pneumoniae/efectos de los fármacos
12.
AIDS Behav ; 18(4): 646-60, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24043269

RESUMEN

A systematic review was conducted to identify evidence-based interventions (EBIs) for increasing HIV medication adherence behavior or decreasing HIV viral load among persons living with HIV (PLWH). We conducted automated searches of electronic databases (i.e., MEDLINE, EMBASE, PsycINFO, CINAHL) and manual searches of journals, reference lists, and listservs. Interventions were eligible for the review if they were U.S.-based, published between 1996 and 2011, intended to improve HIV medication adherence behaviors of PLWH, evaluated the intervention using a comparison group, and reported outcome data on adherence behaviors or HIV viral load. Each intervention was evaluated on the quality of study design, implementation, analysis, and strength of findings. Of the 65 eligible interventions, 10 are EBIs. The remaining 55 interventions failed to meet the efficacy criteria primarily due to null findings, small sample sizes, or low retention rates. Research gaps and future directions for development of adherence EBIs are discussed.


Asunto(s)
Consejo Dirigido , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Cumplimiento de la Medicación/estadística & datos numéricos , Conducta de Reducción del Riesgo , Conducta Sexual/estadística & datos numéricos , Vacunas contra el SIDA/administración & dosificación , Adulto , Condones , Consejo Dirigido/métodos , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Política de Salud , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Asunción de Riesgos , Conducta Sexual/psicología , Estados Unidos
13.
PLoS One ; 8(5): e63365, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23723976

RESUMEN

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1ß) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1ß and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1ß and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses.


Asunto(s)
Antivirales/metabolismo , Bronquios/patología , Células Epiteliales/virología , Mediadores de Inflamación/metabolismo , Interleucina-18/metabolismo , Interleucina-1/metabolismo , Rhinovirus/fisiología , Comunicación Autocrina , Caspasa 1/metabolismo , Células Cultivadas , Activación Enzimática , Células Epiteliales/metabolismo , Células Epiteliales/patología , Células HeLa , Humanos , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Infecciones por Picornaviridae/metabolismo , Infecciones por Picornaviridae/virología , Transducción de Señal , Carga Viral , Internalización del Virus , Replicación Viral
14.
AIDS Behav ; 17(4): 1231-44, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23397183

RESUMEN

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV but few MSM-specific evidence-based interventions (EBIs) have been identified for this vulnerable group. We conducted a systematic review to identify reasons for the small number of EBIs for MSM. We also compared study, intervention and sample characteristics of EBIs versus non-EBIs to better understand the challenges of demonstrating efficacy evidence. Thirty-three MSM-specific studies were evaluated: Nine (27 %) were considered EBIs while 24 (73 %) were non-EBIs. Non-EBIs had multiple methodological limitations; the most common was not finding a significant positive effect. Compared to EBIs, non-EBIs were less likely to use peer intervention deliverers, include sexual communication in their interventions, and intervene at the community level. Incorporating characteristics associated with EBIs may strengthen behavioral interventions for MSM. More EBIs are needed for substance-using MSM, MSM of color, MSM residing in the south and MSM in couples.


Asunto(s)
Terapia Conductista , Bisexualidad/psicología , Identidad de Género , Infecciones por VIH/prevención & control , Homosexualidad Masculina/psicología , Medicina Basada en la Evidencia , Infecciones por VIH/transmisión , Humanos , Masculino , Conducta de Reducción del Riesgo , Parejas Sexuales
15.
Am J Community Psychol ; 50(3-4): 518-29, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22684737

RESUMEN

Translating evidence-based HIV/STD prevention interventions and research findings into applicable HIV prevention practice has become an important challenge for the fields of community psychology and public health due to evidence-based interventions and evidence-based practice being given higher priority and endorsement by federal, state, and local health department funders. The Interactive Systems Framework (ISF) for Dissemination and Implementation and the Division of HIV/AIDS Prevention (DHAP) Research-to-Practice model both address this challenge. The DHAP model and the ISF are each presented with a brief history and an introduction of their features from synthesis of research findings through translation into intervention materials to implementation by prevention providers. This paper describes why the ISF and the DHAP model were developed and the similarities and differences between them. Specific examples of the use of the models to translate research to practice and the subsequent implications for support of each model are provided. The paper concludes that the ISF and the DHAP model are truly complementary with some unique differences, while both contribute substantially to addressing the gap between identifying effective programs and ensuring their widespread adoption in the field.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/prevención & control , Centers for Disease Control and Prevention, U.S./organización & administración , Práctica Clínica Basada en la Evidencia , Infecciones por VIH/prevención & control , Difusión de la Información/métodos , Desarrollo de Programa , Práctica Clínica Basada en la Evidencia/métodos , Práctica Clínica Basada en la Evidencia/organización & administración , Humanos , Modelos Organizacionales , Servicios Preventivos de Salud , Estados Unidos
16.
AIDS Behav ; 16(5): 1092-114, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22234436

RESUMEN

This meta-analysis estimates the overall efficacy of HIV prevention interventions to reduce HIV sexual risk behaviors and sexually transmitted infections (STIs) among heterosexual African American men. A comprehensive search of the literature published during 1988-2008 yielded 44 relevant studies. Interventions significantly reduced HIV sexual risk behaviors and STIs. The stratified analysis for HIV sexual risk behaviors indicated that interventions were efficacious for studies specifically targeting African American men and men with incarceration history. In addition, interventions that had provision/referral of medical services, male facilitators, shorter follow-up periods, or emphasized the importance of protecting family and significant others were associated with reductions in HIV sexual risk behaviors. Meta-regression analyses indicated that the most robust intervention component is the provision/referral of medical services. Findings indicate that HIV interventions for heterosexual African American men might be more efficacious if they incorporated a range of health care services rather than HIV/STI-related services alone.


Asunto(s)
Negro o Afroamericano/psicología , Consejo Dirigido , Seropositividad para VIH/psicología , Heterosexualidad , Enfermedades de Transmisión Sexual/psicología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Atención a la Salud , Seropositividad para VIH/epidemiología , Seropositividad para VIH/transmisión , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Conducta de Reducción del Riesgo , Conducta Sexual , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/transmisión , Estados Unidos/epidemiología
17.
Pulm Pharmacol Ther ; 23(2): 71-7, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19887115

RESUMEN

BACKGROUND: The aim of the present study was to establish whether polymorphisms, especially those within the promoter region, of the beta(2)-adrenoceptor gene (ADRB2) influence beta(2)-adrenoceptor expression in human lung. METHODS: The density of beta-adrenoceptors in human lung tissue (n=88) was determined by saturation binding using the radioligand, iodinated cyanopindolol. Discrimination of beta(1)- and beta(2)-adrenoceptors was determined using the highly selective beta(1)-adrenoceptor antagonist, CGP20712A. Genotype was determined at 5 positions of ADRB2 previously reported as polymorphic. Potential influences of single nucleotide polymorphisms (SNPs) within the promoter region (-367, -47) and coding block (46, 79, 491) of ADRB2 on beta(2)-adrenoceptor expression were investigated. RESULTS: The density of beta(2)-adrenoceptors was variable among the 88 lung preparations studied ranging from 17 to 177fmol/mg protein (mean+/-S.E.M., 72+/-4fmol/mg protein). There was no influence of genotype on beta(2)-adrenoceptor expression for any of the polymorphisms studied except at position 491. The polymorphism at position 491C>T, leading to a change from thr to ile at amino acid 164, is uncommon. Preparations genotyped as heterozygous (126+/-15fmol/mg protein; n=5) expressed significantly (P=0.0005) higher levels of beta(2)-adrenoceptor than those that were homozygous (69+/-4fmol/mg protein; n=83). CONCLUSION: With the exception of position 491, these data indicate that polymorphisms of ADRB2 do not influence beta(2)-adrenoceptor expression in human lung.


Asunto(s)
Expresión Génica , Pulmón/metabolismo , Receptores Adrenérgicos beta 2/genética , Femenino , Genotipo , Humanos , Masculino , Pindolol/análogos & derivados , Pindolol/metabolismo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Unión Proteica , Ensayo de Unión Radioligante
18.
Am J Public Health ; 99(11): 2069-78, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19762676

RESUMEN

OBJECTIVES: We evaluated the efficacy of HIV behavioral interventions for African American females in the United States, and we identified factors associated with intervention efficacy. METHODS: We conducted a comprehensive literature review covering studies published from January 1988 to June 2007, which yielded 37 relevant studies. Data were analyzed using mixed-effects models and meta-regression. RESULTS: Overall, behavioral interventions had a significant impact on reductions in HIV-risk sex behaviors (odds ratio [OR] = 0.63; 95% confidence interval [CI] = 0.54, 0.75; n = 11 239; Cochrane Q(32) = 84.73; P < .001) and sexually transmitted infections (STIs; OR = 0.81; 95% CI = 0.67, 0.98; n = 8760; Cochrane Q(16) = 22.77; P = .12). Greater intervention efficacy was observed in studies that specifically targeted African American females used gender- or culture-specific materials, used female deliverers, addressed empowerment issues, provided skills training in condom use and negotiation of safer sex, and used role-playing to teach negotiation skills. CONCLUSIONS: Behavioral interventions are efficacious at preventing HIV and STIs among African American females. More research is needed to examine the potential contribution of prevention strategies that attend to community-level and structural-level factors affecting HIV infection and transmission in this population.


Asunto(s)
Negro o Afroamericano/psicología , Infecciones por VIH/prevención & control , Educación en Salud , Conducta de Reducción del Riesgo , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Oportunidad Relativa , Estados Unidos
19.
Am J Prev Med ; 32(4 Suppl): S38-67, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17386336

RESUMEN

This article presents the results of a systematic review of the effectiveness and economic efficiency of individual-, group-, and community-level behavioral interventions intended to reduce the risk of acquiring sexually transmitted HIV in adult men who have sex with men (MSM). These results form the basis for recommendations by the Task Force on Community Preventive Services on the use of these interventions. Sexual risk behavior and condom use were the outcomes used to assess effectiveness. Intervention effectiveness on biological outcomes could not be assessed because too few studies of adequate quality have been published. The evidence found in our review shows that individual-level, group-level, and community-level HIV behavioral interventions are effective in reducing the odds of unprotected anal intercourse (range 27% to 43% decrease) and increasing the odds of condom use for the group-level approach (by 81%). The Task Force concluded that the findings are applicable to MSM aged 20 years or older, across a range of settings and populations, assuming that interventions are appropriately adapted to the needs and characteristics of the MSM population of interest. Based on findings from economic evaluation studies, the Task Force also concluded that group- and community-level HIV behavioral interventions for adult MSM are not only cost effective but also result in actual cost savings. Additional information about other effects, barriers to implementation, and research gaps is provided in this paper. The recommendations based on these systematic reviews are expected to serve the needs of researchers, planners, and other public health decision makers.


Asunto(s)
Promoción de la Salud/métodos , Homosexualidad Masculina , Evaluación de Programas y Proyectos de Salud , Conducta de Reducción del Riesgo , Adulto , Humanos , Masculino , Estados Unidos
20.
AIDS Behav ; 11(1): 25-47, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16917668

RESUMEN

This systematic review examines the overall efficacy of HIV behavioral interventions designed to reduce HIV risk behaviors or incident sexually transmitted diseases (STDs) among Hispanics residing in the United States or Puerto Rico. Data from 20 randomized and nonrandomized trials (N = 6,173 participants) available through January 2006 were included in this review. Interventions successfully reduced the odds of unprotected sex and number of sex partners, increased the odds of condom use, and decreased the odds of acquiring new STD infections. Interventions successful in reducing the odds of any sex risk behavior used non-peer deliverers; included >or=4 intervention sessions; taught condom use or problem solving skills; or addressed barriers to condom use, sexual abstinence, or peer norms. Interventions that included the Hispanic cultural belief of machismo or those developed based on ethnographic interviews were successful in reducing the odds of sex risk behaviors among non-drug users. Interventions targeting injection drug users (IDUs; N = 3,569) significantly reduced the odds of injection drug use and the odds of sharing cotton or cookers, but did not significantly reduce the odds of engaging in risky sex behavior or needle sharing. Further development of culturally appropriate HIV prevention interventions for Hispanic populations, particularly men and persons living with HIV, are warranted.


Asunto(s)
Infecciones por VIH/prevención & control , Hispánicos o Latinos , Asunción de Riesgos , Enfermedades de Transmisión Sexual/prevención & control , Femenino , Infecciones por VIH/transmisión , Humanos , Masculino , Puerto Rico/etnología , Conducta Sexual , Enfermedades de Transmisión Sexual/transmisión , Trastornos Relacionados con Sustancias , Estados Unidos
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