Dysfunction of mouse cerebral arteries during early aging

Aging leads to a gradual decline in the fidelity of cerebral blood flow (CBF) responses to neuronal activation, resulting in an increased risk for stroke and dementia. However, it is currently unknown when age-related cerebrovascular dysfunction starts or which vascular components and functions are first affected. The aim of this study was to examine the function of microcirculation throughout aging in mice. Microcirculation was challenged by inhalation of 5% and 10% CO₂ or by forepaw stimulation in 6-week, 8-month, and 12-month-old FVB/N mice. The resulting dilation of pial vessels and increase in CBF was measured by intravital fluorescence microscopy and laser Doppler fluxmetry, respectively. Neurovascular coupling and astrocytic endfoot Ca²⁺ were measured in acute brain slices from 18-month-old mice. We did not reveal any changes in CBF after CO₂ reactivity up to an age of 12 months. However, direct visualization of pial vessels by in vivo microscopy showed a significant, age-dependent loss of CO₂ reactivity starting at 8 months of age. At the same age neurovascular coupling was also significantly affected. These results suggest that aging does not affect cerebral vessel function simultaneously, but starts in pial microvessels months before global changes in CBF are detectable.     

Clinical presentation,therapeutic approach,and outcome of young patients admitted for COVID-19, with respect to the elderly counterpart

There is limited information on the presenting characteristics, prognosis, and therapeutic approaches of young patients hospitalized for coronavirus disease 2019 (COVID-19). We sought to investigate the baseline characteristics, in-hospital treatment, and outcomes of a wide cohort < 65 years admitted for COVID-19. Using the international multicenter HOPE-COVID-19 registry, we evaluated the baseline characteristics, clinical presentation, therapeutic approach, and prognosis of patients < 65 years discharged (deceased or alive) after hospital admission for COVID-19, also compared with the elderly counterpart. Of the included 5746 patients, 2676 were < 65 and 3070 ≥ 65 years. All risk factors and several parameters suggestive of worse clinical presentation augmented through increasing age classes. In-hospital mortality rates were 6.8% and 32.1% in the younger and older cohort, respectively (p < 0.001). Among young patients, mortality, access to ICU and treatment with IMVwere positively correlated with age. Contrariwise, over 65 years of age this trend was broken so that only the association between age and mortality was persistent, while the rates of access to ICU and IMV started to decline. Younger patients also recognized specific predictors of case fatality, such as obesity and gender. Age negatively impacts on mortality, access to ICU and treatment with IMV in patients < 65 years. In elderly patients only case fatality rate keeps augmenting in a stepwise manner through increasing age categories, while therapeutic approaches become more conservative. Besides age, obesity, gender, history of cancer, and severe dyspnea, tachypnea, chest X-ray bilateral abnormalities, abnormal level of creatinine and leucocyte among admission parameters seem to play a central role in the outcome of patients younger than 65 years.

     

Permanent artificial respiration by diaphragm pacemaker in tetraplegic children

This is a study of two children, aged respectively 10 and 6 years, who sustained a spinal cord injury at the C1 C2, causing apnoea. After the bilateral implantation of diaphragm pacemakers and periods of conditioning, they were able to adapt to continuous and simultaneous full-time ventilatory support of both diaphragms without any sign of fatigue, for more than 24 and 11 months, respectively.     

Different Effects of Some Isoquinoline Alkaloids from Argemone mexicana on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examines the effects of the extracts [petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Argemone mexicana on the electrically induced contractions of the isolated guinea-pig ileum (E.C.I.). The results of the experiments indicate that CHCl₃/MeOH (9:1) and MeOH extracts, tested at a concentration of 400, 200 and 100 μg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas the petroleum ether and CHCl₃ extracts did not affect it. Furthermore, the partially purified fractions II–V from the MeOH extract, each tested at concentrations of 200, 100 and 50 μg/mL also inhibited E.C.I. Finally the pure compounds 1–2 (5×10⁻⁶–1×10⁻⁵–5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum, whereas compound 3 (5×10⁻⁶–1×10⁻⁵×10⁻⁵ M ) increased them. Since the active compounds 1–3 were respectively identified as protopine, allocryptopine and berberine by NMR, the observed effects could be related mainly to these compounds. © 1997 by John Wiley & Sons, Ltd.     

Flavonol Glycosides from Croton menthodorus Reduce in vitro Morphine Withdrawal

We currently report the effects of quercetin-3- O -(2- O -ß-apiofuranosyl)-rutinoside (Q), rutin (R), kaempferol-3- O -rutinoside (K) and kaempferol-3- O -(6- O -trans- p -coumaroyl)-ß-D-glucopyranoside (K1) isolated from Croton menthodorus on in vitro morphine withdrawal. The results indicated that all flavonol glycosides tested (1 × 10 -7, 1 × 10 -6, and 1 × 10 -5 M) dose-dependently reduced morphine withdrawal in vitro. These data suggest that flavonol glycosides from Croton menthodorus may play an important role in morphine withdrawal control.     

Intravenous magnesium sulfate administration in a patient with refractory vasospasm following subarachnoid hemorrhage

OBJECTIVE: Magnesium sulfate is being investigated for the prevention or treatment of vasospasm following subarachnoid hemorrhage. PATIENT: A 45-year-old woman suffered subarachnoid hemorrhage and developed after 8 days symptomatic vasospasm in the left middle cerebral artery (MCA) while she was receiving nimodipine prophylactically. METHODS AND RESULTS: Transcranial Doppler monitoring was performed. Cerebral autoregulation was abolished in the left MCA. Despite this finding the administration of a bolus dose of MgSO(4), followed by a continuous infusion in order to achieve serum magnesium levels in the range of 4-4.5 mg/dl (1.65-1.85 mmol/l), resulted in a marked decrease (12.2%) of the left MCA mean blood flow velocity, without clinically relevant change in systemic blood pressure (3%). This effect was maintained for at least 4 h. It did not prevent the development of ischemic lesions.