Maria Antonietta Macrì

Oxygen and life span: chronic hypoxia as a model for studying HIF-1α, VEGF and NOS during aging

To test if oxygen sensitive mechanisms are affected by hypoxia, we studied hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) expression by immunohistochemical analysis in young and old rat carotid bodies (CBs) using hypoxia as a model for modulating aging. Four groups of male age-matched Wistar rats (3 and 24 months) were used. Two groups were kept in room air, and two groups were kept under chronic intermittent hypoxia for 12 days. In aged carotid body and in hypoxia the increased expression of HIF-1alpha, VEGF, iNOS is less evident as compared to the young one. Electron microscopy sections showed a reduced mitochondrial number and area in the aged CBs and during hypoxia. Less responsiveness to hypoxia could be evidenced in the aged rats as compared to the young rats, suggesting an age dependency of the oxygen sensitive mechanisms.

Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: a quantitative proton MRS study

Quantitative proton magnetic resonance spectroscopy (MRS) was used to determine region-specific metabolic changes in young and aged animals subjected to a long-term hypoxic-ischemic injury. Focal ischemia, which was studied as an experimental stroke model, was induced in 3- and 24-month-old rats by unilateral common carotid artery occlusion associated with 24 h of hypoxia. Eight metabolites were quantified from extracts in three different brain regions (hippocampus, frontoparietal and occipital cortices) from both the ipsilateral and contralateral sides. Our findings showed significant differences in lactate and myo-inositol concentration values in the hippocampus of the aged rats as compared to the same area of the young adult group under normoxic conditions. After hypoxia-ischemia (HI), the most relevant changes in metabolite concentrations were found in the hippocampal region of both young and aged groups as compared to their age-matched controls. Of the three brain areas under investigation, the hippocampus proved to be particularly susceptible to the prolonged hypoxia-ischemia perturbation. The effects were more evident in the aged animals.

Measurement of Segmental Transit Through the Gut in Man A Novel Approach by the Biomagnetic Method

The techniques commonly used to evaluate the transit of contents through the gut feature some limitations for being either inaccurate, invasive, inconvenient, or potentially dangerous for the subjects. Aim of this study was to establish a safe, noninvasive and accurate technique for the measurement of segmental oroanal transit time. We localized an orally ingested magnetic marker by means of a biomagnetic instrumentation that allows us to identify in a three-dimensional pattern the position of a biomagnetic source inside the body. The biomagnetic localizations were compared with the anatomical data obtained by magnetic resonance imaging investigations. The study was performed in 12 healthy subjects, and scans were taken every hour up to the arrival of the marker into the cecum; thereafter, scans were taken every 4 hr up to the elimination of the marker. In 99% of the isofield maps obtained from each field scan, the marker was localized within the bowel walls. The mean oroanal transit time was 56±5 hr, the mouth-to-cecum transit time was 13±1.7 hr, and the total colonic transit time was 43.5±5 hr (mean±sem). Segmental colon transit did not show major differences among the regions considered, although most of the time was spent in the right colon. In fact, a good correlation was found between transit time through the right colon and oroanal and total colonic transit (r=0.77,P<0.02,r=0.79,P<0.02 respectively). In conclusion, this method might be a safe alternative to the techniques presently used in the clinical setting for the measurement of intestinal transit.

Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

BackgroundBoth hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old.MethodsCerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate) were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus) from both hemispheres.ResultsIn the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage.ConclusionsWe conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

Biological Effects of Electromagnetic Fields

Nowadays, concerns about hazards from electromagnetic fields represent an alarming source for human lives in technologically developed countries. We are surrounded by electromagnetic fields everywhere we spend our working hours, rest or recreational activities. The aim of this review is to summarize the biological effects due to these fields arising from power and transmission lines, electrical cable splices, electronic devices inside our homes and work-places, distribution networks and associated devices such as cellular telephones and wireless communication tower, etc. Special care has been reserved to study the biological effects of electromagnetic fields on cell lines of the mammalian immune system about which our research group has been working for several years.Molecular biology today appears to be the mainstream interpretative basis for all cellular and pathophysiological phenomena, even going so far as to embrace neuronal and psychic events. The explanation of disease processes, whether genetic or acquired, is sought and, where possible, located in mechanisms consisting in quantitative and/or qualitative modifications of particular molecules making up part of the various anatomical or physiological systems. In relation with the molecular paradigm of disease, also the medical treatment is today founded mostly on the conventional pharmacological approach. However, the need of further research in different fields is suggested by the fact that biological phenomena are characterized by high levels of organization, in which inter-molecular and inter-cellular communications of biophysical nature appear to be involved according to many lines of evidence (Bellavite and Signorini, 1995). As suggested by Kroy (1989), in the living creatures there is an ancestral cybernetic order that is not based on the nervous system or on the humoral system (blood, hormones). This ancestral system is thought to be of an electromagnetic nature, because electromagnetic radiation is the most basic form of information carrier present in nature. Electromagnetic signals have constituted (and still constitute) both the language of communication between atoms and molecules and the means whereby primordial organisms received a series of items of information on the environment (sunlight, other cosmic waves). Living organisms have learnt to use electromagnetism as an information signalling system and even as a means of communication between cells and tissues. According to the studies by Popp and coworkers (Popp 1985; Popp et al. 1989; Ho and Popp 1994), many biological systems are capable of producing, receiving and even of “storing” electromagnetic waves such as light.

Audio to microwave frequency dielectric study of the pretransition region in DPL-water systems

Abstract The phospholipid–water mixtures are used as model systems to investigate the structure and function of biological membranes. The dielectric behaviour of DPPC–water and DPPE–water systems was explored at audio (≥ 2kHz) and microwave (10 GHz) frequencies versus temperature. Particular care was devoted to the pretransition below the main gel-liquid-crystalline phase transition. A possible interpretation of the pretransition mechanism is given in terms of capillary waves.

Carotid Body HIF-1α, VEGF and NOS Expression during Aging and Hypoxia

Carotid body (CB) undergoes several morphological, physiological and biochemical changes during aging, hypoxia and hyperoxia (Di Giulioet al., 1998; Lahiriet al., 1990; Lahiri et al.,2000). CB releases several substances like dopamine, acetilcholine, nerpinephrine, erythropoietin, substance P, and it detects pO2 and pCO2 levels in the blood, it regulates ventilation according to oxygen needs and body requirements for homeostasis maintenence (Bunnet al., 1996). The ventilatory response to hypoxia is characterised by increase in volume and ventilatory frequency in relation to the degree of hypoxia. This response is attenuated with aging (Fukuda 1992) and it is related to the age-dependent structures and function modifications (Guenard 1998), including the basal reduction of oxygen requirements (Sohalet.al,1986, Gunnarsson et al, 1996).

The ripple phase in a DMPC-water mixture. A dielectric investigation

Abstract The dielectric behaviour of a DMPC-water mixture has been investigated in the frequency range from 1 kHz to 10 MHz and in the temperature interval from 0 to 40°C over the crystalline-liquid crystalline phase transition temperatures. A model to explain the dielectric characteristics of the DMPC-water mixture as a function of frequency, and in general for each DPL-water mixture which displays a ripple phase, is proposed. The model is based on the assumption that a particular contribution to the total polarizability comes from the ripple deformation of the bilayer. This contribution is evaluated supposing strong interactions between the lipid head groups with the formation of in-phase domains of correlated electric dipoles. A further assumption relates the extension of the domains to a set of spatial modes, called ripplons, thermally activated in the ripple phase. By the ripplon dispersion relation, the dipole domain extensions (hence the polarizability), were made frequency dependent. The final res...

To what extent are the passive electrical parameters of lymphocyte membranes deduced from impedance spectroscopy altered by surface roughness and microvillosity

Abstract The electrical conductivity of human lymphocyte suspensions in NaCl electrolyte solutions of varying osmolarities has been measured in the frequency range from 1 MHz to 1 GHz, where the ion polarization at the membrane-extracellular medium interface influences markedly the electrical behaviour of the cell suspension. To take into account the complexity of the cytoplasmic membrane, where protrusions and microvillous structures extend towards the extracellular medium, an approach based on scaling concepts typical of the fractal analysis of complex systems is proposed. The passive electrical parameters, i.e. the membrane conductivity σs and the membrane permittivity ϵs, obtained on the basis of this procedure, differ significantly from those derived from conventional methods. The possible relevance of this circumstance from a biological point of view is indicated.

Influence of different glycosphingolipids on the conductometric properties of a model phospholipid membrane system

Abstract The conductometric properties of aqueous solutions of liposomes built up by inserting different gangliosides at different concentrations in a phospholipid bilayer have been investigated in the ratio frequency region, where the alteration of the electrical surface polarization produced in the membrane structure by the ganglioside insertion can be properly observed. We have studied a series of gangliosides (GM1, GM2, GM3, GD1a, GD1b, aGM1) characterized by the same hydrophobic part but with different hydrophilic portions. The results show a quite complex conductivity behaviour that can be only partially accounted for in terms of a surface conductance contribution. Some phenomenological correlations between the hydrophilic head group structure and the electrical conductivity behaviour are presented.