A gravimetric assessment of the Gotthard Base Tunnel geological model: insights from a novel gravity terrain-adaptation correction and rock physics data.

The Gotthard Base Tunnel (GBT) is a 57 km long railway tunnel, constructed in the Central Alps in Switzerland and extending mainly North-South across numerous geological units. We acquired 80 new gravity data points at the surface along the GBT profile and used 77 gravity measurements in the tunnel to test and constrain the shallow crustal, km-scale geological model established during the tunnel construction. To this end, we developed a novel processing scheme, which computes a fully 3D, density-dependent gravity terrain-adaptation correction (TAC), to consistently compare the gravity observations with the 2D geological model structure; the latter converted into a density model. This approach allowed to explore and quantify candidate rock density distributions along the GBT modelled profile in a computationally-efficient manner, and to test whether a reasonable fit can be found without structural modification of the geological model. The tested density data for the various lithologies were compiled from the SAPHYR rock physical property database. The tested models were evaluated both in terms of misfit between observed and synthetic gravity data, and also in terms of correlation between misfit trend and topography of the target profile. The results indicate that the locally sampled densities provide a better fit to the data for the considered lithologies, rather than density data averaged over a wider set of Alpine rock samples for the same lithology. Furthermore, using one homogeneous and constant density value for all the topographic corrections does not provide an optimal fit to the data, which instead confirms density variations along the profile. Structurally, a satisfactory fit could be found without modifying the 2D geological model, which thus can be considered gravimetry-proof. From a more general perspective, the gravity data processing routines and the density-dependent corrections developed in this case study represent a remarkable potential for further high-resolution gravity investigations of geological structures. Supplementary Information: The online version contains supplementary material available at 10.1186/s00015-022-00422-z.

Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study.

PURPOSE: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. METHODS: We studied 2573 men and women aged 50-75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. RESULTS: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. CONCLUSIONS: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes.

Electrophysiological evidence for a reciprocal interaction between amphetamine and cocaine-related drugs on rat midbrain dopaminergic neurons.

To determine the functional interactions occurring between amphetamine and cocaine-like drugs on a single neuron, we used intracellular single-electrode voltage-clamp recordings from dopaminergic cells of the rat midbrain maintained in vitro. In the presence of cocaine (3-30 microM), the outward current caused by amphetamine (100 microM) on cells held at about -60 mV was attenuated. The degree of attenuation of the amphetamine-induced response was almost the same for 3 and 30 microM cocaine (44 and 51% of control, respectively). This effect of cocaine was reversible. We also tested other DA-uptake inhibitors (nomifensine and 4-phenyltetrahydroisoquinoline) against the amphetamine-induced outward current. Both drugs enhanced the effects of dopamine (DA) while reducing the outward response caused by amphetamine. Pretreatment of the animals with reserpine (12 mg/kg/i.p.), which irreversibly depletes the vesicular DA stores, neither affected the amplitude of the current caused by amphetamine nor changed the cocaine-induced attenuation of the membrane responses to amphetamine. Interestingly, when amphetamine (3 microM) was superfused on the dopaminergic neurons prior and during the application of cocaine, the DA-uptake blocker was no longer able to potentiate the outward response caused by the superfusion of DA. Taken together, these data suggest that: (i) amphetamine and cocaine interact with the DA transporter to produce distinct actions which under certain circumstances can compete with each other; (ii) the amphetamine-induced release of DA from the somata and dendrites of the dopaminergic cells is, at least in part, related to the reverse operation of the DA transporter and is not dependent on the integrity of the vesicular content of the catecholamine.

Modification of levodopa responses by deprenyl (selegiline): an electrophysiological and behavioral study in the rat relevant to Parkinson's disease.

From using in vitro intracellular recordings from mesencephalic neurons and monoamine-depleted rats, we report that the functions of levodopa in the brain are greatly enhanced and prolonged by high doses of the monoamine oxidase (MAO) inhibitor deprenyl. Dopaminergic neurons were hyperpolarized and inhibited by levodopa application. These effects of levodopa were largely potentiated by pretreatment with nonselective doses of deprenyl. Furthermore, when locomotor activity induced by levodopa was examined on a rodent model of Parkinson's disease, pretreatment of the animals with nonselective doses of deprenyl caused an enhancement of the antiparkinsonian action of levodopa. The great increase in levodopa responses by deprenyl suggests a likely therapeutic use of this dopamine precursor with a higher dosage of the MAO inhibitor, to reduce effectively the daily levodopa requirements in Parkinson's disease patients.

Monoamine oxidase inhibition causes a long-term prolongation of the dopamine-induced responses in rat midbrain dopaminergic cells.

The way monoamine oxidase (MAO) modulates the depression of the firing rate and the hyperpolarization of the membrane caused by dopamine (DA) on rat midbrain dopaminergic cells was investigated by means of intracellular recordings in vitro. The cellular responses to DA, attributable to the activation of somatodendritic D2/3 autoreceptors, were prolonged and did not completely wash out after pharmacological blockade of both types (A and B) of MAO. On the contrary, depression of the firing rate and membrane hyperpolarization induced by quinpirole (a direct D2 receptor agonist) were not affected by MAO inhibition. Furthermore, although the inhibition of DA reuptake by cocaine and nomifensine caused a short-term prolongation of DA responses, the combined inhibition of MAO A and B enzymes caused a long-term prolongation of DA effects. Moreover, the effects of DA were not largely prolonged during the simultaneous inhibition of MAO and the DA reuptake system. Interestingly, the actions of amphetamine were not clearly augmented by MAO inhibition. From the present data it is concluded that the termination of DA action in the brain is controlled mainly by MAO enzymes. This long-term prolongation of the dopaminergic responses suggests a substitutive therapeutic approach that uses MAO inhibitors and DA precursors in DA-deficient disorders in which continuous stimulation of the dopaminergic receptors is preferable.