ABSTRACT
cAMP plays a significant role in signal transduction pathways controlling multiple cellular processes such as inflammation and immune regulation. cAMP levels are regulated by a family of phosphodiesterases (PDEs). We have studied the effects of a novel PDE7 inhibitor (PDE7i) treatment on mice with experimental autoimmune encephalomyelitis (EAE) a model of multiple sclerosis (MS) and compared it with another PDE7i. EAE was induced by immunizing C57BL/6J mice with myelin oligodendrocyte glycoprotein (MOG35-55) peptide. Mice were treated daily either from disease onset or from disease peak with each PDE7i and with fingolimod (used in therapy for MS patients) and disease evolution was followed by clinical symptoms. We examined neuropathology of spinal cord, ex vivo lymphocyte proliferation by [3H]-thymidine incorporation, TNFα by ELISA and cAMP-PDE mRNAs expression by in situ hybridization histochemistry (ISHH) in spinal cord of EAE mice treated with both PDE7 inhibitors. Treatment of EAE mice with the novel PDE7i, VP3.15 showed more efficacy in reducing clinical signs at 10mgkg-1 than the other PDE7i, BRL50481 and similar to fingolimod. VP3.15 acts on peripheral lymphocytes inhibiting their proliferation and TNFα secretion in a dose-dependent manner. PDE7i treatment alters the levels of PDE4B and PDE7 mRNA expression in EAE mice spinal cord. Given the interest in the development of new drugs for MS, including PDE7i as anti-inflammatory drugs, it is important to study the role played by PDE7 in neurodegenerative diseases with inflammatory component to better understand the beneficial and detrimental effects of a future therapy.
Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 7/antagonists & inhibitors , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Phosphodiesterase Inhibitors/therapeutic use , Animals , Cell Proliferation , Cyclic Nucleotide Phosphodiesterases, Type 7/biosynthesis , Enzyme Inhibitors/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Lymphocytes/pathology , Mice , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/genetics , Myelin-Oligodendrocyte Glycoprotein/metabolism , Peptide Fragments/genetics , Peptide Fragments/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Tumor Necrosis Factor-alpha/metabolismABSTRACT
No disponible
Subject(s)
Middle Aged , Adult , Male , Female , Humans , Motivation , Health Resources , Health Services Needs and Demand , Spain , Risk Factors , Primary Health Care , Venous Thrombosis , Anticoagulants , Cross-Sectional Studies , Cooperative Behavior , Heparin, Low-Molecular-Weight , LeadershipABSTRACT
Objetivo. Determinar la validez de criterio y el valor predictivo del síntoma disuria para el diagnóstico de infección del tracto urinario (ITU). Diseño. Estudio transversal para evaluación de un síntoma. Emplazamiento. Seis consultas de atención primaria (4 de zona urbana y 2 rurales) del Área 11 de Salud de Madrid. Participantes. Se incluyeron 232 pacientes mayores de 14 años que acudieron a consulta durante 6 meses consecutivos (116 consultaron por disuria y 116 asintomáticos para el síntoma disuria). A todos se les solicitó sedimento y urocultivo. Mediciones y resultados. Se estableció diagnóstico de ITU con urocultivo positivo o sedimento con leucocituria y bacteriuria. Se estudio la sensibilidad (S), especificidad (E), el valor predictivo positivo (VPP), el valor predictivo negativo (VPN), el cociente de probabilidades positivo (CPP) y el cociente de probabilidades negativo (CPN) de la disuria para el diagnóstico de ITU. La edad media fue de 54 años (rango, 19-82), siendo un 73 por ciento mujeres. No había diferencias significativas de edad y sexo entre casos y no casos (p > 0,1). La disuria mostró una S del 96 por ciento (IC del 95 por ciento, 86-98 por ciento), una E del 69 por ciento (IC del 95 por ciento, 61-76 por ciento) y un CPP de 3,1 (IC del 95 por ciento, 2,7-3,5) para el diagnóstico de ITU. En el subgrupo de mujeres la S fue del 95 por ciento (IC del 95 por ciento, 84-99 por ciento) y la E del 67 por ciento (IC del 95 por ciento, 58-75 por ciento). Se calculó para este síntoma un VPP del 30 por ciento (IC del 95 por ciento, 22-40 por ciento) y un VPN del 99 por ciento (IC del 95 por ciento, 95-100 por ciento). Conclusiones. Es poco probable el diagnóstico de ITU sin el síntoma disuria. La mayoría de los pacientes con ITU presentan disuria; sin embargo, este síntoma aislado no nos permite establecer el diagnostico de infección urinaria (AU)
Subject(s)
Male , Female , Humans , Urinary Tract Infections , Urination Disorders , Reproducibility of Results , Case-Control Studies , Cross-Sectional Studies , Predictive Value of TestsABSTRACT
OBJECTIVE: To assess the validity of criterion and predictive value of dysuria for the diagnosis of UTI. DESIGN: Cross-sectional study to assess a symptom. SETTING: Six general medicine clinics (four urban clinics and two rural clinics) in the 11th Health Area in Madrid. PATIENTS: The sample consists of 232 patients aged above fourteen who consulted during six consecutive months (116 of them reported having dysuria and 116 were asymptomatic). MEASUREMENTS AND MAIN RESULTS: The diagnosis of urinary tract infections (UTI) was achieved through positive urine cultures or bacteriuria and leukocyturia in the centrifuged urine sediment. The sensitivity (S) of dysuria analysis for the diagnosis of UTI, its specificity (E), its predictive value (VP), and its probability coefficient (CP) were considered. Average age of the sample was 54 years old (range 19-82); 73% of the patients were female. No statistically significative difference of sex and age was found between cases and non-cases (p > 0.1). Dysuria showed a 96% of sensitivity (95% CI, 86-98%), a 69% of E (95% CI, 61-76%) and 3.1 of CPP (95% CI, 2.7-3.5) for UTI diagnosis. In the women subgroup there was 95% of sensitivity (95% CI, 84-99%) and 67% of E (95% CI, 58-75%). A positive predictive value of 30% (95% CI, 22-40) and a negative predictive value of 99% (95% CI, 95-100) were estimated for this symptom. CONCLUSIONS: The diagnosis of urinary tract infections is unlikely in the absence of dysuria, but to treat all dysuria patients as UTI entails a high rate of overtreatment.
Subject(s)
Urinary Tract Infections/complications , Urination Disorders/etiology , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Predictive Value of Tests , Reproducibility of Results , Urinary Tract Infections/diagnosis , Urinary Tract Infections/microbiologyABSTRACT
OBJECTIVES: To find the clinical and epidemiological characteristics of HIV-positive patients and to study the possible differences between patients attended by primary care teams (PCT) and by the hospital specialist unit (SU). DESIGN: A descriptive cross-sectional study. SETTING: Six PCTs in Villaverde, Usera and Carabanchel (Madrid). PATIENTS: Those infected with HIV and in the morbidity records between January 1992 and January 1995. MEASUREMENTS AND MAIN RESULTS: 274 cases were studied. The most important risk practice was being IDU (intravenous drugs user) (80.3%). The most definitive and linked AIDS-related illness was Tuberculosis (39.7%). Patients treated with Zidovudine (or AZT) were monitored by PCTs (p = 0.004), as were those not needing day-hospital treatment (p = 0.0005). CONCLUSIONS: HIV infection in our environment follows the typical clinical and epidemiological pattern of this country: transmitted by IDUs, with its most frequent associated infection being tuberculosis. With the exception of AZT or day-hospital treatment, its clinical and epidemiological features are similar in PCTs and SUs. Information and responsible participation of PCT professionals in caring for HIV-positive patients are the key strategies for guaranteeing the quality of health care delivery.
Subject(s)
Acquired Immunodeficiency Syndrome/epidemiology , HIV Infections/epidemiology , HIV-1 , Primary Health Care , Urban Population/statistics & numerical data , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/therapy , Acquired Immunodeficiency Syndrome/therapy , Adult , Cross-Sectional Studies , Female , HIV Infections/therapy , Humans , Male , Primary Health Care/statistics & numerical data , Risk Factors , Spain/epidemiology , Survival AnalysisSubject(s)
Calcium/administration & dosage , Food, Fortified , Adolescent , Adult , Aged , Female , Humans , Middle Aged , Nutritional Requirements , Osteoporosis/prevention & controlSubject(s)
Alcoholism/complications , Pellagra/complications , Adult , Female , Humans , Male , Middle Aged , Niacinamide/therapeutic use , Pellagra/drug therapySubject(s)
Cross Infection/epidemiology , Respiratory Tract Infections/epidemiology , Adolescent , Adult , Age Factors , Aged , Child , Cross Infection/etiology , Female , Hospital Departments , Hospitals, General , Humans , Length of Stay , Male , Middle Aged , Prospective Studies , Respiratory Tract Infections/etiology , Sex Factors , Streptococcal Infections/epidemiology , Tuberculosis, Pulmonary/epidemiology , Urinary Tract Infections/epidemiologyABSTRACT
Duodenal microflora was studied in three groups of malnourished infants: I) 10 cases with acute diarrhea; II) six carbohydrate intolerant infants; III) eight cases with cow's milk protein intolerance. In all of them it was observed linear increases of overgrowing flora, with a greater incidence of Gram negative microorganisms. The greatest number of bacterial counts, with mixed flora was found in group III. In group II, "Escherichia coli" was present in all the cultured aspirates, suggesting that it was not a random fact, and could be the agent responsible of diarrhea.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/microbiology , Diarrhea, Infantile/microbiology , Duodenum/microbiology , Milk Proteins/metabolism , Nutrition Disorders/microbiology , Animals , Carbohydrate Metabolism, Inborn Errors/complications , Cattle , Diarrhea, Infantile/complications , Enterobacteriaceae/isolation & purification , Female , Humans , Infant , Infant, Newborn , Nutrition Disorders/complications , Staphylococcus aureus/isolation & purificationABSTRACT
Duodenal microflora was studied in two groups of infants in their first month of life with normal nutritional status: I) 11 infants with acute diarrhea; II) 3 infants with carbohydrate intolerance. No modifications of microflora were found in group I. Meanwhile in group II bacterial counts were always present from 10(3) to indefinite col/ml, being frequent the presence of Gram negative bacteria, with almost half of occasions positive to "Escherichia coli". Duodenal microflora alterations were independent of diarrheal duration and the same than those described in other ages of life.
