Evaluaci?n de la asociaci?n meloxicam atorvastatina sobre la respuesta neuronal y glial en un modelo murino de isquemia cerebral por embolismo arterial

147 p. Recurso Electr?nicoEl accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, siendo m?s del 85% de origen isqu?mico. Se estudi? el efecto de la atorvastatina y el meloxicam en forma ?nica y asociada sobre la respuesta neuronal, astrocitaria y microglial en un modelo de infarto cerebral por embolia arterial. Se emplearon 32 ratas Wistar hembras sometidas a embolia arterial carotidea y posterior tratamiento con meloxicam, atorvastatina y su asociaci?n a 6, 24, 48 y 72 horas; se evalu? la reactividad de las prote?nas COX-2, GFAP y OX-42 como marcadores de la actividad de la enzima ciclooxigenasa 2, los astrocitos y la microgl?a respectivamente, empleando la t?cnica de inmunohistoqu?mica convencional. La neurodegeneraci?n, la supervivencia celular y la integridad de la mielina fueron evaluadas utilizando las tinciones Flourojade y Luxol Fast Blue (m?todo Kluver Barrera modificado), mediante an?lisis densitom?trico y morfol?gico. Los datos obtenidos fueron evaluados empleando an?lisis de varianza y pruebas no param?tricas de comparaci?n m?ltiple. La isquemia cerebral por embolia arterial increment? significativamente (p<0,001) la reactividad astrocitaria y microglial, en tanto, la atorvastatina, el meloxicam y su asociaci?n la redujeron. La isquemia produjo acortamiento de las proyecciones astrocitarias, engrosamiento celular, ruptura de las expansiones protopl?smicas (clasmatodendrosis) y cambios morfol?gicos microgliales propios de diversas etapas de actividad. En zonas perifocales, se increment? la inmunoreactividad de COX-2 y se redujo en el foco isqu?mico; en tanto, el meloxicam y la atorvastatina redujeron significativamente la inmunoreactividad perifocal, restableciendo el marcaje de COX-2 en el foco isqu?mico. En conclusi?n, la asociaci?n meloxicam ? atorvastatina aten?a la respuesta astrocitaria y microglial del proceso inflamatorio luego de la isquemia cerebral por embolia arterial, reduciendo la neurodegeneraci?n y restableciendo el equilibrio morfol?gico y funcional del enc?falo.Stroke is the second leading cause of death and the first of disability in the world, with more than 85% of the cases having ischemic origin. To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin to 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Neurodegeneration, cells survival and myelin integrity were analyzed with Fluoro Jade and Luxol Fast Blue (Kluver`s Barrera method modified). Data were evaluated by analysis of variance and non-parametric multiple comparison. Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p <0.001), whereas it was reduced by single or associated treatments with atorvastatin and meloxicam. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various stages of activity. In perifocal areas, the immunoreactivity of COX-2 was increased in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p <0.001) the perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. These results suggest that meloxicam?atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring morphological and functional balance of nervous tissue. Keywords: astrocytes, microglia, atorvastatin, brain ischemia, cyclooxygenase, meloxicam

Evaluaci?n de la asociaci?n Meloxicam-Atorvastatina sobre la respuesta neuronal y glial en un modelo murino de isquemia cerebral por embolismo arterial

147 p. Recurso Electr?nicoEl accidente cerebrovascular es la segunda causa de muerte y la primera de discapacidad en el mundo, siendo m?s del 85% de origen isqu?mico. Se estudi? el efecto de la atorvastatina y el meloxicam en forma ?nica y asociada sobre la respuesta neuronal, astrocitaria y microglial en un modelo de infarto cerebral por embolia arterial. Se emplearon 32 ratas Wistar hembras sometidas a embolia arterial carotidea y posterior tratamiento con meloxicam, atorvastatina y su asociaci?n a 6, 24, 48 y 72 horas; se evalu? la reactividad de las prote?nas COX-2, GFAP y OX-42 como marcadores de la actividad de la enzima ciclooxigenasa 2, los astrocitos y la microgl?a respectivamente, empleando la t?cnica de inmunohistoqu?mica convencional. La neurodegeneraci?n, la supervivencia celular y la integridad de la mielina fueron evaluadas utilizando las tinciones Flourojade y Luxol Fast Blue (m?todo Kluver Barrera modificado), mediante an?lisis densitom?trico y morfol?gico. Los datos obtenidos fueron evaluados empleando an?lisis de varianza y pruebas no param?tricas de comparaci?n m?ltiple. La isquemia cerebral por embolia arterial increment? significativamente (p<0,001) la reactividad astrocitaria y microglial, en tanto, la atorvastatina, el meloxicam y su asociaci?n la redujeron. La isquemia produjo acortamiento de las proyecciones astrocitarias, engrosamiento celular, ruptura de las expansiones protopl?smicas (clasmatodendrosis) y cambios morfol?gicos microgliales propios de diversas etapas de actividad. En zonas perifocales, se increment? la inmunoreactividad de COX-2 y se redujo en el foco isqu?mico; en tanto, el meloxicam y la atorvastatina redujeron significativamente la inmunoreactividad perifocal, restableciendo el marcaje de COX-2 en el foco isqu?mico. En conclusi?n, la asociaci?n meloxicam ? atorvastatina aten?a la respuesta astrocitaria y microglial del proceso inflamatorio luego de la isquemia cerebral por embolia arterial, reduciendo la neurodegeneraci?n y restableciendo el equilibrio morfol?gico y funcional del enc?falo.Stroke is the second leading cause of death and the first of disability in the world, with more than 85% of the cases having ischemic origin. To evaluate in an embolism model of stroke the effect of atorvastatin and meloxicam on neurons, astrocytes and microglia. This evaluation was done administering each medication individually and in association. Wistar rats were subjected to carotid arterial embolism and treatment with meloxicam and atorvastatin to 6, 24, 48 and 72 hours. Using immunohistochemistry, we evaluated the immunoreactivity of COX-2 protein, GFAP and OX-42 in neurons, astrocytes and microglia by densitometric and morphological studies. Neurodegeneration, cells survival and myelin integrity were analyzed with Fluoro Jade and Luxol Fast Blue (Kluver`s Barrera method modified). Data were evaluated by analysis of variance and non-parametric multiple comparison. Cerebral ischemia by arterial embolism increased significantly the reactivity of microglia and astrocytes (p <0.001), whereas it was reduced by single or associated treatments with atorvastatin and meloxicam. Ischemia produced astrocytic shortening, cellular thickening, protoplasmic rupture expansions (clasmatodendrosis) and microglial morphological changes characteristic of various stages of activity. In perifocal areas, the immunoreactivity of COX-2 was increased in the ischemic focus it was reduced, while meloxicam and atorvastatin significantly reduced (p <0.001) the perifocal immunoreactivity, restoring the marking of cyclooxygenase in the ischemic focus. These results suggest that meloxicam?atorvastatin association attenuates astrocytic and microglial response in the inflammatory process after cerebral ischemia by arterial embolism, reducing neurodegeneration and restoring morphological and functional balance of nervous tissue. Keywords: astrocytes, microglia, atorvastatin, brain ischemia, cyclooxygenase, meloxicam

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization