Acute optic nerve lesions in first-ever NMOSD-related optic neuritis using conventional brain MRI: A Latin American multicenter study.

BACKGROUND: Few studies regarding MRI-defined acute optic nerve lesions (aONL) in patients with first-ever neuromyelitis optica spectrum disorder (NMOSD)-related optic neuritis (ON) have been reported worldwide and none of them was conducted in Latin America (LATAM). Therefore, we aimed to assess the frequency of aONL at disease onset using conventional brain MRI in LATAM. METHODS: We reviewed the medical records and brain MRIs (≤30 days from ON onset) of patients with ON as first lifetime NMOSD attack. Patients from Argentina (n=48), Ecuador (n=24), Brazil (n=22), Venezuela (n=10) and Mexico (n=8) were included, and further divided into two subgroups according to either presence (P-MRI) or absence (A-MRI) of aONL (T2 hyperintensity and/or contrast enhancement). Clinical, paraclinical, imaging and prognostic data were compared. RESULTS: A total of 112 patients were included and aONL were found in 86 (76.7%) at disease onset. Aquaporin-4 antibodies were detected in 69.6%. Non-Caucasian patients comprised 59.8% of the total cohort. In P-MRI, conventional brain MRI showed isolated or combined unilateral (54.4%, [8.5% of these aONL were associated with chiasmatic lesions]) and bilateral (46.6%, [35.9% of these aONL were associated with chiasmatic lesions]) lesions. Thus, 100% of chiasmatic lesions were associated with unilateral or bilateral lesions. No statistically significant differences were found in age, gender, ethnicity, clinical course, mean follow-up time, disability, and spinal cord MRI findings. However, rituximab use was higher in P-MRI than in A-MRI (p=0.006). CONCLUSIONS: More than three quarters of LATAM patients with first-ever NMOSD-related ON have aONL detected by brain MRI. Unilateral lesions were the most common finding. Further studies including different ethnicities are needed to assess the generalizability of our results.

Brain magnetic resonance imaging features in multiple sclerosis and neuromyelitis optica spectrum disorders patients with or without aquaporin-4 antibody in a Latin American population.

INTRODUCTION: There is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients. METHODS: We retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included. RESULTS: We included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p<0.001, CT = p<0.001, PBVL p = 0.01). CONCLUSION: Different MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI.

Clinical features and prognosis of late-onset neuromyelitis optica spectrum disorders in a Latin American cohort.

BACKGROUND: We aimed to assess the clinical, paraclinical, imaging and prognostic features of patients with late-onset neuromyelitis optica spectrum disorder (LO-NMOSD; ≥ 50 years at disease onset) LO-NMOSD, compared with early onset-NMOSD (EO-NMOSD, ≤ 49 years at disease onset), in Latin American (LATAM). METHODS: We retrospectively reviewed the medical records of patients with NMOSD, as defined using the 2015 validated diagnostic criteria. We included patients from Argentina, Brazil and Venezuela. They were divided into: LO-NMOSD and EO-NMOSD and comparison among the groups were performed. RESULTS: Among these 140 NMOSD patients, 24 (17.1%) were LO-NMOSD; 64% were positive for aquaporin-4 antibodies; and 41.5% of this population cohort was non-Caucasian. Severe disability [expanded disability status scale (EDSS) ≥ 6] at the last follow-up and presence of comorbidities were significantly associated with LO-NMOSD, compared with EO-NMOSD. LO-NMOSD patients had a shorter median time to EDSS ≥ 4 than EO-NMOSD patients (46 vs. 60 months; log-rank test p = 0.0006). Furthermore, we observed a positive correlation between age at onset and EDSS score at the last follow-up (Spearman r = 0.34, p < 0.0001). CONCLUSION: LO-NMOSD patients from LATAM developed early severe disability, compared with EO-NMOSD. Therefore, age at onset could have important implications for the long-term prognosis of NMOSD patients.

Brain and spinal MRI features distinguishing MS from different AQP4 antibody serostatus NMOSD at disease onset in a cohort of Latin American patients.

OBJECTIVE: We aimed to evaluate magnetic resonance imaging (MRI) previously used criteria (Matthews's criteria, MC) for differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD) in Caucasian and non-Caucasian populations (Argentina, Brazil and Venezuela) with positive (P-NMOSD), negative (N-NMOSD), and unknown (U-NMOSD) aquaporin-4 antibody serostatus at disease onset and to assess the added diagnostic value of spinal cord MRI in these populations. METHODS: We reviewed medical records, and MRIs were assessed by two blinded evaluators and were scored using MC. Short-segment transverse myelitis (STM) was added as a new criterion. MC sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: We included 282 patients (MS = 188 and NMOSD = 94). MC applied to the entire cohort showed 97.8% sensitivity, 82.9% specificity, 92.0% PPV, and 95.1% NPV for differentiating MS from NMOSD. A subanalysis applied only to non-Caucasian (MS = 89 and NMOSD = 47) showed 100% sensitivity, 80.8% specificity, 90.8% PPV, and 100% NPV. Similar sensitivity, specificity, PPV, and NPV of MC for MS versus P-NMOSD (n = 55), N-NMOSD (n = 28), and U-NMOSD (n = 21) were observed. CONCLUSION: MC distinguished MS from NMOSD of all serostatus in a Latin American cohort that included non-Caucasian populations. Addition of STM to MC did not raise the accuracy significantly.

Preparation of La0.7Ca0.3-xSrxMnO3 Manganites by Four Synthesis Methods and Their Influence on the Magnetic Properties and Relative Cooling Power.

Manganites of the family La0.7Ca0.3-xSrxMnO3 were fabricated by four preparation methods: (a) the microwave-assisted sol-gel Pechini method; (b) sol-gel Pechini chemical synthesis; (c) solid-state reaction with a planetary mill; and (d) solid-state reaction with an attritor mill, in order to study the effect of the preparation route used on its magnetocaloric and magnetic properties. In addition, the manganites manufactured by the Pechini sol-gel method were compacted using Spark Plasma Sintering (SPS) to determine how the consolidation process influences its magnetocaloric properties. The Curie temperatures of manganites prepared by the different methods were determined in ~295 K, with the exception of those prepared by a solid-state reaction with an attritor mill which was 301 K, so there is no correlation between the particle size and the Curie temperature. All samples gave a positive slope in the Arrot plots, which implies that the samples underwent a second order Ferromagnetic (FM)⁻Paramagnetic (PM) phase transition. Pechini sol-gel manganite presents higher values of Relative Cooling Power (RCP) than the solid-state reaction manganite, because its entropy change curves are smaller, but wider, associated to the particle size obtained by the preparation method. The SPS technique proved to be easier and faster in producing consolidated solids for applications in active magnetic regenerative refrigeration compared with other compaction methods.

First Order Reversal Curve Study of SmFe2 Melt-Spun Ribbons.

First-order reversal curves (FORC) and the FORC distribution provide a detailed characterization of the relative proportions of reversible and irreversible components of the magnetization of a material, revealing the dominant interactions in the system. Alloys with the nominal composition SmFe2 were obtained by melt-spinning with a cooper wheel velocity of 30 m/s. X-ray powder diffraction analysis showed a greater part consisting of an amorphous phase and a very small amount of SmFe2 crystalline phase with an average crystallite size of 8 nm. A constant acceleration Mössbauer spectrum, measured at room temperature in transmission mode, was fitted to a continuous distribution of effective fields at the nucleus of the amorphous phase (about 84% of the total area), plus two sextets for the non-equivalent sites of Fe in the SmFe2 crystalline phase. 91 first-order reversal curves were collected in a Quantum Design PPMS-VSM with reversal fields from ⁻800 mT to +800 mT and using a calibration field of 850 mT. The obtained FORC diagrams showed a combined effect of a local interaction field and a mean interaction field, and showed that the reversible magnetization is a function of both, the applied magnetic field and the irreversible magnetization.

Effects of indomethacin on prostanoid synthesis and vasomotor responsiveness in endothelium-denuded abdominal and thoracic aortas of Wistar rats.

In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas. Enzyme immunoassay data supported direct evidence of phenylephrine-stimulated release of prostanoids (PGI2, PGE2, and PGF2α) by thoracic and abdominal aortas without endothelium, and their almost complete inhibition by 1 µM indomethacin. Isometric force measurements established that 10 µM indomethacin-but no lower concentrations-inhibited the contractions evoked by phenylephrine in endothelium-denuded abdominal aorta. In this preparation, 10 µM indomethacin also depressed the contractions provoked by angiotensin II and high K+ (80 mM). In fact, indomethacin (up to 1 mM) caused concentration-dependent reductions in all abovementioned contractile responses. In endothelium-denuded thoracic aortas, however, only 1 mM indomethacin significantly depressed the contractile activity stimulated by either phenylephrine, angiotensin II, or high K+. Hence, there was a clear quantitative difference in response to indomethacin between abdominal and thoracic aortas without endothelium. Altogether, the results indicate that prostanoids induced by phenylephrine in abdominal and thoracic aortas were derived from non-endothelial COX-mediated metabolism; notably, the decrease in prostanoid synthesis could not account for the inhibition of vasoconstrictor responses by indomethacin: Through COX-independent actions, indomethacin inhibited aortic smooth muscle contractility.

Activation of upregulated angiotensin II type 2 receptors decreases carotid pulse pressure in rats with suprarenal abdominal aortic coarctation.

Our aim was to determine whether angiotensin type 2 receptors (AT2R) are involved in the depression of carotid pulse pressure (PP) in rats with suprarenal aortic coarctation (SrC). We tested the effects of losartan, PD123319, and CGP42112 on PP in SrC and Sham-operated anesthetized rats. PP increased in SrC rats. Neither losartan nor PD123319 affected PP in SrC and Sham-operated rats. CGP42112 reduced PP, in SrC rats, combined with losartan. Moreover, PD123319 blocked this effect. AT2R protein increased in the thoracic aortas of SrC rats. Thus, upregulated AT2R stimulation by CGP42112 mediates depression of PP in rats under pressure overloading.

Acute intravenous injection and short-term oral administration of N(G) -nitro-L-arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension, but not inhibition of acetylcholine-induced hypotensive responses.

In experiments in vivo, we studied whether the endothelial dysfunction induced by nitric oxide (NO) synthesis inhibition is simultaneously or sequentially manifested as a reduced level of endothelium-dependent agonist-induced vasodilatation, an increased responsiveness to vasoconstrictors, and hypertension. Vascular responses to acetylcholine, phenylephrine, and angiotensin II were measured in pithed rats after acute intravenous injection (100 mg/kg) and short-term oral administration of N(G) -nitro-L-arginine methyl ester (L-NAME; 60 mg/kg per day) for 1 and 3 days (L-NAME(1d) and L-NAME(3d), respectively). Pithed rats were chosen because drug-induced cardiovascular responses reflect only peripheral effects. Parallel experiments examined mean arterial pressure (MAP) values in anesthetized rats. After short-term L-NAME(1d) and L-NAME(3d) treatments, the MAP was significantly elevated in anesthetized but not pithed rats. Acute intravenous administration of L-NAME elevated MAP in pithed rats. Intravenous infusion of phenylephrine was used to compensate for the pressor response induced by L-NAME in pithed animals. The maximum decrease and duration of the hypotensive responses to acetylcholine were unaltered by the acute and both short-term L-NAME treatments in pithed rats. These treatments, on the other hand, increased phenylephrine- and angiotensin II-induced pressor responses in pithed animals. In isolated aortic rings prepared from pithed rats treated acutely and short-term with L-NAME, acetylcholine-induced relaxations were inhibited. Thus, the inhibition of NO-dependent vasodilator tone after acute intravenous injection and short-term oral L-NAME administration may be associated with vascular smooth muscle hyper-responsiveness to pressor agonists and hypertension, whereas the hypotensive responses to acetylcholine could not be associated with the L-NAME-induced endothelial dysfunction in pithed rats.

Microlithiasis of the epididymis and the rete testis.

Testicular microlithiasis is a well-defined clinical and pathologic entity easily diagnosed through testicular echography; however, its association with cancer and infertility is now under debate. Many efforts have been done in recent years to clarify the spectrum of lesions observed in testicular microlithiasis, but no published data as to the existence of a possible microlithiasis of the epididymis and the rete testis have been found. We have observed microlithiasis of the epididymis and the rete testis in surgical (8 epididymis and 6 testis) and autopsy specimens (12 cases). In decreased order of frequency, microliths of the proximal spermatic way were seen in rete testis, epididymal duct, and efferent ducts. Intraluminal, subepithelial, and interstitial microliths were localized along these segments of the spermatic way. Subepithelial microliths were the most frequently found. A granulomatous reaction around the interstitial epididymal microliths, mimicking malacoplakia, was observed in 1 case. The differential diagnosis of microliths includes corpora amilacea, Michaelis-Gutmann bodies, calcium deposits, hyaline globules, and parasites, like the giant kidney worm Dioctophyme renale. In infants and young adults, microlithiasis of the epididymis and the rete testis is frequently associated with alterations in the development of the proximal spermatic way. In elderly adults, it is related to ischemia and obstruction of the spermatic way.

Analisis clinico epidemiologico de factores asociados a malformaciones congenitas ECLAMC-Hospital Universitario San Ignacio junio-diciembre de 2001 / Epidemiological and clinical analysis of associated factors at congenital malformations ECLAMC-Hospital Universitario San Ignacio jun.-dic. 2001

El Instituto de Genética Humana de la Pontificia Universidad Javeriana inició la investigación clínica y epidemiológica de malformaciones congénitas en el Hospital Universitario San Ignacio (HUSI) en asocio con el Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). Objetivo: determinar la prevalencia global de malformaciones congénitas y que variables del estudio ECLAMC-HUSI tienen mayor fuerza de asociación con la presencia de alformaciones congénitas en el HUSI. Método: se realizó un estudio con dos modalidades operativas caso-control y cohorte histórica durante el período del 1º de junio al 31 de diciembre del 2001. Se consideraron en el programa todos los nacimientos, vivos de cualquier peso o muertos mayores a 500 g ocurridos en la sala de partos del HUSI. No se consideraron los nacimientos ocurridos fuera del hospital. Para cada paciente malformado se diligenció la ficha de caso y la ficha para su respectivo control exceptuando los mortinatos malformados a los cuales solamente se les llenó solamente la ficha de caso. Resultados: el número total de nacimientos durante este período fue de 2026. El promedio de nacimientos estimado por mes fue de 289,43 (D.E. ñ52,19). El número total de malformados fue de 87 con un promedio de 12,43 (D.E. ñ3,15) malformados por mes y una prevalencia global de 4,29 por ciento (D.E. ñ1,44 por ciento). El total de nacimientos vivos fue de 199S de los cuales 81 (4,05 por ciento) presentaron malformaciones y el total de nacimientos muertos fue de 24 de los cuales 6 (21,4 por ciento) presentaron malformaciones. Las malformaciones encontradas en ECLAMC-HUSI se describen en la tabla 2. Los factores que se encontraron asociados significativamente a la presencia de malformaciones fueron: el rango de edad de 25-29 (p<0.05), vaginosis (p<0.01), las enfermedades crónicas (p<0,01) y los factores físicos (p<0,05). No se encontró significancia estadística en la distribución por sexo, medicamentos, instituciones de adopción, metrorragia e inmunizaciones. Conclusión: los resultados obtenidos son la primera aproximación para conocer la frecuencia y los factores de riesgo asociados con recién nacidos malformados en el HUSI y generan nuevas posibilidades para la realización de otros estudios de este tipo en otros hospitales de Bogotá y de la región

Evaluation of the total content of antioxidants in complex mixtures

There exists a variety of procedures to evaluate the total content of antioxidants in complex mixtures such as biological fluids or plant extracts. Based on these procedures, different indexes (TRAP, TAR, ORAC) have been proposed to quantify the level of the antioxidant status of the fluid. Depending upon the procedure employed, these indexes measure the total concentration of antioxidants and/or their ability to modulate the steady state concentration of the active free radicals in the system. In the present article most of the experimental procedures that can be employed to evaluate the total content of antioxidants in complex samples are reviewed, with special emphasis on the information that can be obtained from this type of measurements.