Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery

The aim of this study was to evaluate the effect of vaginal delivery on both ACTH and catecholamines (DA, NE, E) secretion in the mother, the fetus (umbilical artery) and the newborn. Blood samples were obtained from 19 normal pregnant women and the corresponding umbilical cords, and from the newborns. Seventeen normal nonpregnant women, matched for age and parity, were also included in the study as "nonpregnant controls". The results demonstrate that in the mother, plasma catecholamines (CA) concentrations during labor and delivery are elevated above the values reported for normal nonpregnant women and there is a predominant E response. The concentrations of CA in umbilical arteries are very high compared to those in the corresponding mother and they fall rapidly after birth. Unlike that in the mother, the predominant CA response to parturition in the fetus and newborn infant is NE. The extraction rate of DA, NE and E from placenta is approximately 60%. The peripheral plasma levels of ACTH in pregnant women during labor are twice and 10 times as high as those observed in the corresponding umbilical arteries and in nonpregnant women respectively. At delivery they increase further. No significant differences are found between the values measured in the arterial cord blood and those in the venous cord blood and in the newborns. A way of explaining the prevalence of E and the higher ACTH/E ratio found in the mother in comparison with the fetus could be that in the mother the stress response to parturition is regulated mainly by the pituitary-adrenal axis, whereas in the fetus there is a prevalent stimulation of the sympathetic nervous system.     

Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis: an expert opinion

Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients’ preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients’ preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.

     

Prevalence of stroke and stroke-related disability in Valle d’Aosta, Italy

Population ageing and improved healthcare may lead to an increase in the prevalence of stroke. The aim of this study is to investigate the prevalence of stroke and stroke-related disability in a population sample resident in Aosta, Italy. The information was collect using a simple questionnaire for first ever stroke in the past combined with the analysis of the patients’ medical records and integrated with the information reported by six general practitioners. 102 cases of stroke were identified in the study population of 6,930 subjects, for an overall prevalence per 1,000 inhabitants of 1.4 (95% CI 0.81–1.99), which increased to 4.79 (95% CI 3.29–6.29) in subjects aged ≥65 years. Fifty-nine percent of the cases were completely or partially dependent (Rankin scores of 2–5). At the time of interview, 72% were living at home. Our data do not reveal any increase in the prevalence of stroke, possibly because of a reduced incidence of the disease.     

POLR3A variants in hereditary spastic paraparesis and ataxia: clinical,genetic, and neuroradiological findings in a cohort of Italian patients

Neurological Sciences - Mutations in POLR3A are characterized by high phenotypic heterogeneity, with manifestations ranging from severe childhood-onset hypomyelinating leukodystrophic syndromes to...     

Melatonin and its brain metabolite N1‐acetyl‐5‐methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice

Melatonin prevents mitochondrial failure in models of sepsis through its ability to inhibit the expression and activity of both cytosolic (iNOS) and mitochondrial (i‐mtNOS) inducible nitric oxide synthases. Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed the existence of changes in iNOS/i‐mtNOS and their relation with mitochondrial dysfunction in the MPTP model of PD, which also displays increased iNOS expression. We also evaluated the role of melatonin (aMT) and its brain metabolite, N¹‐acetyl‐5‐methoxykynuramine (AMK), in preventing i‐mtNOS induction and mitochondrial failure in this model of PD. Mitochondria from substantia nigra (SN) and, to a lesser extent, from striatum (ST) showed a significant increase in i‐mtNOS activity, nitrite levels, oxidative stress, and complex I inhibition after MPTP treatment. MPTP‐induced i‐mtNOS was probably related to mitochondrial failure, because its prevention by aMT and AMK reduced oxidative/nitrosative stress and restored complex I activity. These findings represent the first experimental evidence of a potential role for i‐mtNOS in the mitochondrial failure of PD and support a novel mechanism in the neuroprotective effects of aMT and AMK. © 2009 Wiley‐Liss, Inc.     

The spectrum of MR detectable cortical microinfarcts: a classification study with 7-tesla postmortem MRI and histopathology

Cerebral microinfarcts (CMIs) are common neuropathologic findings in aging and dementia. We explored the spectrum of cortical CMIs that can be visualized with 7T magnetic resonance imaging (MRI). Thirty-three coronal brain slices of 11 individuals with neuropathologically confirmed dementia were subjected to a high-resolution postmortem 7T MRI protocol. First, we identified all visible small (⩽5 mm) intracortical and juxtacortical lesions on postmortem MRI. Lesions were classified as CMI or nonCMI based on histology, and their MR features were recorded. Thirty lesions were identified on the initial MRI evaluation, of which twenty-three could be matched with histology. Histopathology classified 12 lesions as CMIs, all of which were located intracortically. On the basis of their MR features, they could be classified as chronic gliotic CMIs—with or without cavitation or hemorrhagic components—and acute CMIs. Eleven MRI identified lesions were not of ischemic nature and most commonly enlarged or atypically shaped perivascular spaces. Their MRI features were similar to gliotic CMIs with or without cavitation, but these ‘CMI mimics'' were always located juxtacortically. 7T postmortem MRI distinguishes different histopathologic types of cortical CMIs, with distinctive MR characteristics. On the basis of our findings, we propose in vivo rating criteria for the detection of intracortical CMIs.     

Primate type-C virus nucleic acid sequences (woolly monkey and baboon types) in tissues from a patient with acute myelogenous leukemia and in viruses isolated from cultured cells of the same patient.

Cultured peripheral blood leukocytes from a woman (patient HL23) with acute myelogenous leukemia produced type-C RNA tumor viruses (HL23V). The viruses were analyzed by molecular hybridization experiments after transmission to five secondary cell culture lines. Using the criteria of molecular hybridization, we concluded that all of the transmitted virus isolates have nucleotide sequences related to the genome of simian sarcoma virus (SiSV). In addition, in agreement with data reported elsewhere, some of the transmitted viruses also have nucleotide sequences related to those of the baboon endogenous virus (BaEV). We also used molecular hybridization to ascertain whether both viruses could have originated from the patient HL23. Utilizing [3H] cDNA complementary to RNA from the separated BaEV-related component of HL23V and hybridizing this cDNA to DNA from tissues of the patient, we detected sequences related to BaEV in DNA obtained from the patient's spleen. These BaEV DNA sequences were also detectable when 125I-labeled RNA from BaEV was used as a probe. In agreement with earlier results, however, no SiSV-related sequences were detectable in the DNA of her tissues. Cytoplasmic viral-like particles, which had a buoyant density of 1.15-1.2 g/ml and were capable of synthesizing cDNA in association with a 35S RNA in vitro, were also found in the patient's fresh uncultured leukemic blood cells. cDNA synthesized by the cytoplasmic particles contained some sequences that hybridized to RNA from SiSV and, in addition, some that hybridized to RNA from BaEV. The cDNA also hybridized significantly to DNA isolated from the spleen of patient HL23 and to cytoplasmic RNA from the patient's leukocytes. These molecular hybridization results with nucleic acids obtained from the fresh blood cells of the patient, combined with the repeated isolation of similar viruses from different blood and bone marrow samples from the same patient, suggest that the virus come directly from the leukemic cell samples. The finding of BaEV-related DNA proviral sequences in the spleen of the patient strongly supports this interpretation. The failure so far to find a complete SiSV-related provirus is perplexing, but could be attributable to the existence of such a provirus in DNA of only a small population of cells in most leukemic patient.     

Food Insecurity Among Hispanic/Latino Youth: Who Is at Risk and What Are the Health Correlates?

Purpose

We examined the correlates and health implications of household food insecurity among Hispanic/Latino youth (aged 8–16 years), a high food insecurity–risk population.