RESUMEN
OBJECTIVES: The aim of the study was to evaluate the potential role of chemokine receptor CXCR4 and its ligand CXCL12 in the pathogenesis of abdominal aortic aneurysm (AAA). METHODS: AAA tissue specimens were obtained from the anterior or lateral aneurysm sac of patients (n = 32, 26 males, 6 females; 66.8 ± 11.2 years, diameter 64.4 ± 17.0 mm), who underwent elective open surgical repair. Twelve non-aneurysmal aortic specimens from transplant donors served as controls. Expression analysis of CXCR4 and CXCL12 at mRNA and protein level was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining of corresponding histological sections for CD3 (T-cells), CD20 (B-cells), and CD68 (macrophages) was performed to determine the cellular localization of CXCR4 and CXCL12. Data were analyzed with SPSS 20.0 using Mann-Whitney U test and Spearman's rank correlation coefficient. RESULTS: Gene expression of CXCR4 and CXCL12 was 9.6 and 4.6 fold higher in AAA than in non-aneurysmal aorta (p = .0004 and p < .0001, respectively). Likewise, the protein level of CXCR4 was increased 3.2 fold in AAA wall compared with non-aneurysmal aortic tissue (p < .0001), although CXCL12 could not be detected. Immunohistochemical analysis revealed that CXCR4 was expressed in B and T lymphocytes and macrophages, and CXCL12 was observed only in plasma cells. CONCLUSIONS: This study confirmed the over expression of CXCR4 in human AAA tissue. CXCR4 was detected both at the mRNA and the protein level and by immunohistochemistry, especially in inflammatory cells. In contrast, CXCL12 expression was observed only at the mRNA level, with the exception of plasma cells. The exact role of CXCR4/CXCL12 in AAA has to be further elucidated.
Asunto(s)
Aorta Abdominal/química , Aneurisma de la Aorta Abdominal/metabolismo , Mediadores de Inflamación/análisis , Receptores CXCR4/análisis , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/cirugía , Aortografía/métodos , Biomarcadores/análisis , Western Blotting , Estudios de Casos y Controles , Quimiocina CXCL12/análisis , Quimiocina CXCL12/genética , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores CXCR4/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tomografía Computarizada por Rayos X , Regulación hacia ArribaRESUMEN
INTRODUCTION: Patients with depression frequently report painful physical symptoms. However, there are scant data from the UK concerning differences in primary and secondary care resource use between depressed patients with and without pain treated in general practice. METHODS: Patients with depression codes were identified from the General Practice Research Database (GPRD) excluding those with psychoses. The observation period was 1st January 2000-31st December 2006. Patients were further categorised into three groups: (i) no painful physical symptom codes ever in the observation period (NO PAIN); (ii) patients with no other diagnostic or test codes 30 days either side of a pain code (PAIN MINUS DIAGNOSIS) and (iii) patients with pain codes and other diagnostic codes (PAIN PLUS DIAGNOSIS). Rates of general practitioner (GP) visits, antidepressant and concomitant prescribing and switching, secondary care referrals and diagnostic tests were reported per group with 95% confidence limits (CI). RESULTS: A total of 145,784 patients with depression aged 18-50 years were selected. Of these, 48,615 (33.3%) were classed as NO PAIN, the remaining 66.6% having pain. PAIN MINUS DIAGNOSIS patients constituted 5654 (5.8%) of those with pain. PAIN MINUS DIAGNOSIS and PAIN PLUS DIAGNOSIS had a significantly higher rate of GP visits than NO PAIN patients, 10.37 (95% CI 10.23, 10.52); 11.15 (11.11,11.20) and 7.04 (7.00, 7.08) respectively. Inter and intraclass drug switching was high with 13% of PAIN MINUS DIAGNOSIS and 14% of PAIN PLUS DIAGNOSIS patients having three or more switches compared with 7% of NO PAIN patients. Referral rates to secondary care were significantly higher in both pain groups compared with patients with no pain. Diagnostic testing was significantly greater in PAIN MINUS DIAGNOSIS and PAIN PLUS DIAGNOSIS groups than NO PAIN patients for all test types, with X-rays being the most common test; 3.85 (3.69,4.00); 2.77 (2.74,2.80); 0.91 (0.89, 0.94) respectively. CONCLUSION: Patients in general practice diagnosed with depression and concurrent painful physical symptoms have higher resource use in primary and secondary care.