-
[show abstract]
[hide abstract]
ABSTRACT: Metabolic syndrome (MetS) is a disorder characterized primarily by the development of insulin resistance. Insulin resistance and subsequent hyperinsulinemia, originating from abdominal obesity, increases the risk of cerebrovascular and cardiovascular disease and all-cause mortality. Obesity is probably a risk factor for Alzheimer's disease and vascular dementia and is associated with impaired cognitive function. The obese Zucker rat (OZR) represents a model of type 2 diabetes exhibiting a moderate degree of arterial hypertension and of increased oxidative stress. To clarify the possible relationships between MetS and brain damage, the present study has investigated brain microanatomy in OZRs compared with their littermate controls lean Zucker rats (LZRs). Male OZRs and LZRs of 12 weeks of age were used. Their brain was processed for immunochemical and immunohistochemical analysis of glial fibrillary acidic protein (GFAP). In frontal and parietal cortex of OZRs a significant increase in the number of GFAP immunoreactive astrocytes was observed. Similar findings were found in the hippocampus, where an increased number of GFAP immunoreactive astrocytes were detected in the CA1 and CA3 subfields and dentate gyrus of OZRs compared to the LZRs. These findings indicating the occurrence of brain injury accompanied by astrogliosis in OZRs suggest that these rats developed as an animal model of type 2 diabetes, may also represent a model for assessing the influence of MetS on brain.The identification of neurodegenerative changes in OZRs may represent the first step for better characterizing neuronal involvement in this model of metabolic syndrome and possible treatments for countering it.
Neuroscience Letters 03/2013; · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress is an imbalance between the production of free radicals and antioxidant defense mechanisms, potentially leading to tissue damage. Oxidative stress has a key role in the development of cerebrovascular and/or neurodegenerative diseases. This phenomenon is mainly mediated by an enhanced superoxide production by the vascular endothelium with its consequent dysfunction. Thioctic, also known as alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid), is a naturally occurring antioxidant that neutralizes free radicals in the fatty and watery regions of cells. Both the reduced and oxidized forms of the compound possess antioxidant ability. Thioctic acid has two optical isomers designated as (+)- and (-)-thioctic acid. Naturally occurring thioctic acid is the (+)-thioctic acid form, but the synthetic compound largely used in the market for stability reasons is a mixture of (+)- and (-)-thioctic acid. The present study was designed to compare the antioxidant activity of the two enantiomers versus the racemic form of thioctic acid on hydrogen peroxide-induced apoptosis in a rat pheochromocytoma PC12 cell line. Cell viability was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and free oxygen radical species (ROS) production was assessed by flow cytometry. Antioxidant activity of the two enantiomers and the racemic form of thioctic acid was also evaluated in spontaneously hypertensive rats (SHR) used as an in vivo model of increased oxidative stress. A 3-h exposure of PC12 cells to hydrogen peroxide (H(2)O(2)) significantly decreased cell viability and increased levels of intracellular ROS production. Pre-treatment with racemic thioctic acid or (+)-enantiomer significantly inhibited H(2)O(2)-induced decrease in cell viability from the concentration of 50 μmol/L and 20 μmol/L, respectively. Racemic thioctic acid and (+)-salt decreased levels of intracellular ROS, which were unaffected by (-)-thioctic acid. In the brain of SHR, the occurrence of astrogliosis and neuronal damage, with a decreased expression of neurofilament 200 kDa were observed. Treatment of SHR for 30 days with (+)-thioctic acid reduced the size of astrocytes and increased the neurofilament immunoreaction. The above findings could contribute to clarify the role played by thioctic acid in central nervous system injury related to oxidative stress. The more pronounced effect of (+)-thioctic acid observed in this study may have practical therapeutic implications worthy of being investigated in further preclinical and clinical studies.
International Journal of Molecular Sciences 01/2013; 14(3):4580-95. · 2.60 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Arterial hypertension is the main risk factor for stroke and plays a role in the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). An association between hypertension and reduced cerebral blood flow and VCI is documented and arterial hypertension in midlife is associated with a higher probability of cognitive impairment. These findings suggest that arterial hypertension is a main cause of vascular brain disorder (VBD). Spontaneously hypertensive rat (SHR) is the rat strain most extensively investigated and used for assessing hypertensive brain damage and treatment of it. They are normotensive at birth and at 6months they have a sustained hypertension. Time-dependent rise of arterial blood pressure, the occurrence of brain atrophy, loss of nerve cells and glial reaction are phenomena shared to some extent with hypertensive brain damage in humans. SHR present changes of some neurotransmitter systems that may have functional and behavioral relevance. An impaired cholinergic neurotransmission characterizes SHR, similarly as reported in patients affected by VaD. SHR are also characterized by a dopaminergic hypofunction and noradrenergic hyperactivity similarly as occurs in attention-deficit with hyperactivity disorder (ADHD). Microanatomical, neurochemical and behavioral data on SHR are in favor of the hypothesis that this strain is a suitable model of VBD. Changes in catecholaminergic transmission put forward SHR as a possible model of ADHD as well. Hence SHR could represent a multi-faced model of two important groups of pathologies, VBD and ADHD. As for most models, researchers should always consider that SHR offer some similarities with corresponding human pathologies, but they do not suffer from the same disease. This paper reviews the main microanatomical, neurochemical and behavioral characteristics of SHR with particular reference as an animal model of brain vascular injury.
Journal of the neurological sciences 06/2012; 322(1-2):241-9. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present investigation is to study the effects of DEX or E2 treatment during differentiation towards neural cell line of rat BM-MSCs in culture. In order to better characterize biochemically
our in vitro model, we evaluate by western blotting and immunocytochemical analysis some neural lineage markers (nestin, neurofilament,
β-tubulin) and MAP-Kinases. An enhanced expression of the neural markers and MAP-Kinase in DEX-treated BM-MSCs cultures is
found. In addition, E2-treatment increases MAP-Kinase and β-tubulin expression, but it decreases nestin and neurofilament expression. In conclusion,
our findings highlight a significant up and down modulation of nestin, neurofilament, β-tubulin and MAP-Kinases expression
in neurosteroids-treated BM-MSCs. In particular, our results clarify the molecular mechanism involved during eventual differentiation
of these stem cells treated with DEX and E2, addressed towards a neural cell line, that may express neurotrophic receptors and release neurotrophines particularly implicated
during neurogenesis processes.
KeywordsCell cultures-Dexamethasone-Estradiol-Mesenchymal stem cells-Neural markers
Neurochemical Research 04/2012; 35(12):2154-2160. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The influence of one week treatment with the choline-containing phospholipids cytidine-5'-diphosphocholine (CDP-choline) and choline alphoscerate (L-alpha-glyceryl-phosphorylcholine) at choline-equivalent doses (CDP-choline: 325 mg/kg/day; choline alphoscerate: 150 mg/kg/day) on vesicular acetylcholine transporter (VAChT), on choline transporter (CHT) and on acetylcholine (ACh) concentrations was investigated in rat frontal cortex, striatum and cerebellum. ACh was assayed by HPLC with electrochemical detection, VAChT by Western blot, ELISA and immunohistochemistry, CHT by Western blot and immunohistochemistry. After CDP-treatment, ACh levels were slightly increased in the frontal cortex, not substantially different in the striatum, and reduced significantly in the cerebellum compared to controls. Choline alphoscerate stimulated significantly the neurotransmitter concentration in the frontal cortex, however, the levels were similar to the controls in both the striatum and cerebellum. In comparison to the controls, VAChT expression following either CDP-choline or choline alphoscerate treatment, was enhanced greatly in the striatum and cerebellum. Also, ELISA measurements for VAChT showed significant increases in all choline alphoscerate treated brain areas. In contrast, in the CDP-choline treated rats the vesicular transporter amount was greater than the control only in the striatum. The cholinergic presynaptic transporters VAChT and CHT play a relevant role in sustaining new ACh synthesis and release. To sum up, CDP-choline and choline alphoscerate stimulated to a different extent the expression of VAChT and CHT primarily in a cognitive area such as frontal cortex. In the lack of novel therapeutic strategies, safe compounds developed since a long time such as the choline-containing phospholipids investigated would merit to be further investigated by new and adequate clinical studies. This for assessing their place if any in pharmacotherapy of dementia disorders characterized by diminished cholinergic tone.
Journal of the neurological sciences 03/2011; 302(1-2):49-57. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Arterial hypertension is a well-known risk factor for stroke and cognitive deterioration of vascular origin, including vascular
cognitive impairment (VCI) and vascular dementia (VaD). Patients with ischemic VaD have a significantly greater incidence
of hypertension than patients with dementia of the Alzheimer’s type. Areas of white matter (WM) hyperintensity and ventricular
enlargement are more common in hypertensive subjects compared with that in normotensive individuals. An association between
hypertension and reduced cerebral blood flow (CBF) and VCI is documented. Hypertension in midlife is associated with a higher
probability of cognitive impairment than hypertension developed later in life. These findings collectively indicate that arterial
hypertension is a main cause of vascular brain disorder (VBD).
In this chapter, the main characteristics of cerebrovascular and brain damage in spontaneously hypertensive rats (SHR) and
stroke-prone (SP) SHR are reviewed. SHR and SHR-SP are two widely used animal models of hypertension and hypertension plus
stroke, respectively. They are normotensive at birth and gradually develop severe hypertension in the first 2–4 months of
life. At 6 months, they have developed a sustained hypertension. SHR were the model most extensively investigated for assessing
hypertensive brain damage and treatment of it. The time-dependent rise of arterial blood pressure, the occurrence of brain
atrophy, loss of nerve cells, and glial reaction are phenomena shared to some extent with hypertensive brain damage in humans.
SHR, therefore, can represent a reasonable model of morphological damage induced by hypertension and possibly reversed by
appropriate antihypertensive treatment.
From a neurotransmitter point of view, SHR present changes of some specific neurotransmitter systems that may have functional
and behavioral relevance. An impaired cholinergic neurotransmission characterizes both SHR and SHR-SP, similarly as reported
in patients affected by VaD. The possibility that cholinergic neurotransmission mechanisms contribute to central nervous system
plasticity or may improve brain circulation in this animal model is suggested by some studies. SHR are also characterized
by a dopaminergic hypofunction and noradrenergic hyperactivity. This causes an imbalance between noradrenergic hyperfunction
and dopaminergic hypofunction similarly as occurs in attention-deficit with hyperactivity disorder (ADHD).
The majority of microanatomical, behavioral, and neurochemical data on SHR are in favor of the hypothesis that this strain
is a suitable model of VBD. Changes in catecholaminergic transmission put forward SHR as a possible model of ADHD as well.
Hence, SHR could represent a multifaced model of two important groups of pathologies, VBD and ADHD. As for most models, researchers
should always consider that SHR offer some similarities with corresponding human pathologies, but they do not suffer from
the same disease.
Key wordsHypertension–Hypertension plus stroke–Rat model–Vascular dementia
12/2010: pages 577-611;
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the present investigation is to study the effects of DEX or E(2) treatment during differentiation towards neural cell line of rat BM-MSCs in culture. In order to better characterize biochemically our in vitro model, we evaluate by western blotting and immunocytochemical analysis some neural lineage markers (nestin, neurofilament, β-tubulin) and MAP-Kinases. An enhanced expression of the neural markers and MAP-Kinase in DEX-treated BM-MSCs cultures is found. In addition, E(2)-treatment increases MAP-Kinase and β-tubulin expression, but it decreases nestin and neurofilament expression. In conclusion, our findings highlight a significant up and down modulation of nestin, neurofilament, β-tubulin and MAP-Kinases expression in neurosteroids-treated BM-MSCs. In particular, our results clarify the molecular mechanism involved during eventual differentiation of these stem cells treated with DEX and E(2), addressed towards a neural cell line, that may express neurotrophic receptors and release neurotrophines particularly implicated during neurogenesis processes.
Neurochemical Research 10/2010; 35(12):2154-60. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aquaporins (AQP) 1 and 4 are water channel proteins localized respectively at the level of the blood-cerebrospinal fluids (CSF) and blood brain (BBB) barriers. These barriers represent the sites of exchange between blood and nervous tissue and between blood, choroid plexus and CSF in brain ventricles respectively. Damage of these barriers may alter transfer of substances between blood and nervous tissue. In spontaneously hypertensive rats (SHR) chronic hypertension may induce BBB dysfunction and pronounced defects in the integrity of the blood-CSF barrier. AQP1 is expressed in the apical membrane of choroid plexus epithelium. AQP4 is expressed by astrocyte foot processes near blood vessels. The present study has assessed the expression of AQP1 and AQP4 in the brain of SHR in pre-hypertensive (2 months of age), developing hypertension (4 months of age) and established hypertension (6 months of age) stages. Age-matched Wistar-Kyoto (WKY) rats were used as normotensive reference group. AQP1 expression is increased in choroid plexus epithelium of 6-month-old SHR. An increased expression of AQP4 was found in frontal cortex, striatum, and hippocampus of 4- and 6-month-old SHR compared to younger cohorts and age-matched WKY rats. These findings suggest that the increase in AQP expression may alter fluid exchange in BBB and/or in blood-CSF barrier. This situation in case of an acute or excessively elevated rise of blood pressure can promote BBB changes causing the brain damage occurring in this animal model of hypertension.
Brain research 02/2010; 1325:155-63. · 2.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The two major intermediate filament (IF) proteins of astrocytes are vimentin and GFAP. Early during development, radial glia and immature astrocytes express mainly vimentin. Towards the end of gestation, a switch occurs whereby vimentin is progressively replaced by GFAP in differentiated astroglial cells. The expression of vimentin and GFAP increased markedly after injury to CNS. GFAP has been widely recognized as an astrocyte differentiation marker, constituting the major IF protein of mature astrocyte. In our recent researches we investigated the interactions between growth factors and dexamethasone on cytoskeletal proteins GFAP and vimentin expression under different experimental conditions. In addition, nestin, a currently used marker of neural stem cells, is transiently co-expressed with GFAP during development and is induced in reactive astrocytes following brain injury. The role of S100B in astrocytes, neurons, and microglia is particularly studied in Alzheimer's disease. In conclusion, such glial biomarkers will help us to understand the more general mechanisms involved in CNS development and can open new perspectives for the control of the neurologic diseases.
Frontiers in bioscience (Scholar edition) 01/2010; 2:558-70.
-
[show abstract]
[hide abstract]
ABSTRACT: Spontaneously hypertensive rats (SHR), which are normotensive at birth and develop sustained hypertension between 3 and 6 months of age, are the model most extensively investigated for evaluating hypertensive brain damage and its treatment. The time-dependent rise of arterial blood pressure and the occurrence of brain atrophy, loss of nerve cells and glial reaction are shared to some extent with what occurs human hypertensive brain. SHR, therefore, can represent a reasonable model of hypertension-related brain damage. Our main studies on cerebrovascular and brain microanatomical changes occurring in SHR and their sensitivity to pharmacological interventions are summarized.
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 01/2010; 115(1-2):13-7.
-
[show abstract]
[hide abstract]
ABSTRACT: Three diets were compared for the feeding of captive common sole broodstock (Solea solea) kept under ambient photoperiod and temperature conditions. A group of 70 adults were caught in the wild and the 38 males and 32 females distributed at random in six tanks. All the fish were acclimated to the same semi-moist diet (M) in the pre-experimental period from December to February. Three dietary treatments were offered in the experimental period from March to May with two replicates (tanks) per treatment. The treatments were M alone, M supplemented with fresh mussels (Mytilus edulis) (M+M), and M supplemented with live polychaetes (Perinereis cultrifera) (M+P). Spawning occurred during April and May when water temperature was 17 and 18 degrees C, respectively, and salinity around 34-35ppt. Average daily dry matter intake expressed as a proportion of body weight was M 0.65+/-0.34%, M+M 0.43+/-0.18%, and M+P 0.56+/-0.27%, and differed significantly (P<0.05) between treatments. The average daily dry matter intake within a tank ranged from 0.31+/-0.04% in February to 0.98+/-0.26% in May (P<0.05), apparently due to changes in the photo-thermal regime. Diet significantly affected the number of days when spawning occurred, the number of days when hatched eggs were produced, and the proportion of fertilized eggs (P<0.05); and affected the number of days on which viable eggs were produced during April (NS). In all cases, the results were lowest for M+M, while those for the other two treatments did not differ significantly. Differences in hatching rate were not significant in April. During May, no spawning occurred in fish given the M+M treatment, and the differences between the other two treatments were not significant. Values for all variates tended to be higher for M+P than M+M in April and lower for M+P and M in May. These results suggest that supplementing the semi-moist diet with mussels depressed feed intake and, consequently, reproductive performance; the semi-moist diet alone and semi-moist diet supplemented with polychaetes allowed satisfactory food intake and reproductive performance in broodstock sole.
Animal reproduction science 07/2009; 113(1-4):167-76. · 1.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nicardipine is a dihydropyridine-type Ca(2+) channel blocker (CCB) with strong antihypertensive activity and with a peculiar cerebrovascular profile. This paper has reviewed the main controlled clinical studies on nicardipine in pathologies associated with cerebrovascular impairment. Subarachnoid haemorrhage (SAH) is managed with CCBs to prevent vasospasm and improve clinical outcomes. Nimodipine is the CCB licensed for this indication. Former studies did not demonstrate an advantage of nicardipine versus nimodipine in SAH. A more recent approach administering the drug intra-arterially or using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits and improved clinical outcome after severe SAH. Nicardipine is recommended for elevated blood pressure after acute ischemic stroke or intracerebral haemorrhage and is effective in prevention of stroke. More recent investigations were focused on the treatment of cognitive deterioration of vascular origin. In this setting nicardipine has been investigated in more than 6000 patients, with improvement of cognitive deterioration in more than 60% of patients treated. The anti-hypertensive activity of nicardipine, its safety and effectiveness in cognitive domain, suggests re-considering this drug in the treatment of cognitive impairment of vascular origin and for reducing the risk of recurrent stroke in patients at high risk of it.
Journal of the neurological sciences 04/2009; 283(1-2):219-23. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The present study was designed to assess if treatment with acetylcholinesterase inhibitor galantamine and the cholinergic precursor choline alphoscerate (alpha-glyceryl-phosphoryl-choline) alone or in association has any protective effect on brain microanatomy in spontaneously hypertensive rats (SHR) used as an animal model of vascular dementia (VaD). Thirty-two-week-old SHR and age-matched normotensive Wistar Kyoto (WKY) rats were left untreated or treated for 4 weeks with an oral dose of 3 mg/kg/day of galantamine, of 100 mg/kg/day of choline alphoscerate or their association. The number of neurons and of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, phosphorylated neurofilament, and microtubule associated protein-2 (MAP-2) and aquaporin-4 (AQP-4) was assessed by quantitative microanatomical and immunohistochemical techniques. In SHR, the number of neurons of frontal cortex, of the CA1 subfield of hippocampus and of dentate gyrus was decreased compared to WKY rats. Astrogliosis, breakdown of phosphorylated neurofilament, unchanged MAP-2 and altered AQP-4 expression were found as well. Both galantamine and choline alphoscerate countered nerve cell loss. Choline alphoscerate but not galantamine decreased astrogliosis and restored expression of AQ-4. Galantamine countered to a greater extent than choline alphoscerate phosphorylated neurofilament breakdown. The two drugs in association displayed a more remarkable effect. This study confirms a neuroprotective effect of galantamine in SHR and indicates a neuroprotective role of choline alphoscerate in the same model. A wider neuroprotective effect of the cholinergic inhibitor/precursor association was observed. These findings suggest to assess the activity of this cholinergic association in clinical trials.
Journal of the neurological sciences 04/2009; 283(1-2):187-94. · 2.32 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this work was to assess the effects of hexavalent chromium [Cr(VI)] on shoe, leather, and hide industry workers, based on the assumption that Cr(VI) can behave as an environmental immunological "stressor."
The immunological patterns of 84 male subjects were studied in relation to Cr(VI) hematic and urinary levels. Cr(VI) was measured through atomic absorption. Lymphocyte subsets, mitogen-mediated lymphocyte-proliferation, cytokine levels, and natural killer (NK) cytotoxic activity were also assayed.
The urinary levels of the total amount of Cr(VI) were significantly higher in a subgroup of exposed subjects (group B) than in the control or in the lower exposed (group A). In group B, Cr(VI) caused a decrease in the density of glucocorticoid receptors (GR) on peripheral blood mononuclear cells (PBMC) and a increase of IL-6. Cr(VI) did not modify NK-mediated cytotoxicity, the plasmatic levels of inflammatory cytokines and related soluble receptors, and prostaglandin levels, while it tended to increase lymphocyte sensitivity to mitogens and the production of immunomodulant cytokines (IFN-gamma, IL-4, and IL-2). The experimental addition of Cr(VI) to the in vitro lymphocyte culture determined a significant inhibition of phagocytosis percentage, index, and killing percentage. These effects were neutralized by exogenous IFN-gamma.
Cr(VI) could represent an environmental immunological stressor whose effects can be evaluated through laboratory surveys. The lymphocyte mitogen-induced proliferation, GR receptor on PBMC, and IL-6 plasma levels may represent a discriminating element between Cr(VI)-induced stress and other kinds of stress.
Environmental Toxicology 01/2009; 24(6):594-602. · 2.41 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study has investigated, under controlled conditions, peripheral mononuclear cells (PMNC) subset redistribution in a human experimental stress model consisting of cycloergometer activity in healthy male volunteers exposed to a stressful stimulus. After stressful stimuli, leucocyte subpopulations undergo a stereotyped redistribution peculiar for each PMNC cytotype. PMNC subpopulations involved to a greater extent were natural killer (NK) cells and lymphocytes T "memory" cells. The post-stress period was characterized by a decrease of the NK subpopulation. Our findings confirm the view of a sensible functional reduction of immunocompetence in stress conditions. This brings to the opening, even if for a short time, an "immunological window." This window remains open throughout the time of the stimulus, probably representing the basis of the progressive reduction of the competency of immune system. Catecholamines support the acute effects of stress influencing the anatomical redistribution of lymphocyte subpopulation and intermediating acute effects on PMNC. Cortisol, acting for longer time, contributes to create and maintain both the neutrocytosis and lymphopenia in the post-stress period following lymphocytosis.
Clinical and Experimental Hypertension 12/2008; 30(8):720-31. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Nimodipine is a 1,4-dihydropyridine-derivative Ca(2+)-channel blocker developed approximately 30 years ago. It is highly lipophilic, crosses the blood-brain barrier, and reaches brain and cerebrospinal fluid. Early treatment with nimodipine reduces the severity of neurological deficits resulting from vasospasm in subarachnoid haemorrhage (SAH) patients. In SAH, nimodipine reduced spasm-related deficits of all severities, but no spasm-unrelated deficits. This paper has reviewed preclinical studies on the influence of nimodipine in various animal models of cerebral ischemia, with particular attention toward investigations published in the last 10 years. These studies further support the main indication of nimodipine, by clarifying some mechanisms of the anti-ischemic activity of the compound. Papers reporting a possible role of nimodipine in epileptogenesis were also examined. Clinical studies on nimodipine were grouped into subarachnoid hemorrhage, acute ischemic stroke, cerebral ischemia without stroke, dementia disorders, and migraine. Clinical investigations have shown that the drug improves neurological outcome by reducing the incidence and severity of ischemic deficits in patients with SAH from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition. No relevant effects of treatment with nimodipine were reported for acute ischemic stroke, cerebral ischemia without stroke, and migraine, except than for cluster headache. The less pronounced cardiovascular effects of nimodipine compared to other dihydropyridine-type Ca(2+)-channel blockers probably accounts for its use out of label for treating patients affected by chronic cerebral ischemia and vascular cognitive impairment. However, the blood pressure-lowering effects of nimodipine should not be minimized, as clinical studies have documented lowering blood pressure in small groups of patients, including cases of withdrawn due to pronounced hypotension induced by nimodipine administration. In the area of vascular cognitive impairment, short-term benefits of nimodipine do not justify its use as a long-term anti-dementia drug, and benefits obtained in elderly patients affected by subcortical vascular dementia require to be confirmed by other groups and in larger scale trials. In conclusion, nimodipine is a safe drug with an important place in pharmacotherapy and with the main documentation for reduction in the severity of neurological deficits resulting from vasospasm in SAH patients.
Clinical and Experimental Hypertension 12/2008; 30(8):744-66. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was designed to evaluate in healthy volunteers plasma and cellular (in erythrocytes) of three formulations of alpha-lipoic acid (ALA) available in Italy with different rates of absorption, two with a claimed high absorption rate (Byodinoral 600 QR, Tiocronal 600 HR) and one with a claimed prolonged absorption rate (Tiobec 600 retard). These formulations were compared with the registered ethic formulation of the compound (Thioctacid 600 mg HR), available in Germany. Area under the curve from time 0 to last measured time (AUC(t)), peak plasma concentration (C(max)) of ALA, and time (T(max) ) at which C(max) was observed were the plasma kinetic parameters measured. Concentration of ALA at different sampling times was the only parameter assessed for erythrocytes. The AUC(t) values were similar for the four formulations of ALA tested. C(max) was significantly higher for Byodinoral 600 QR, Tiocronal 600 HR compared to Thioctacid 600 mg HR or Tiobec 600 retard, whereas T(max) value was significantly shorter for Byodinoral 600 QR in the order by Tiocronal 600 HR, Thioctacid 600 mg HR, and Tiobec 600 retard. ALA concentrations that accumulated in erytrocytes after the administration of the different formulations of the antioxidant are directly proportional to the plasma levels of each formulation. Because antioxidant capabilities of ALA depend on the glutathione regeneration the compound induces in cells, the most rationale approach for eliciting antioxidant activity at the cellular level is probably in the use of a formulation allowing the compound to reach its target at highest concentrations and in the shortest time.
Clinical and Experimental Hypertension 12/2008; 30(8):767-75. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The present work has used controlled conditions to study how physical activity and stress affect oxidant and anti-oxidant systems in a human model. Stress test consisting of one hour exercise at a cycloergometer with intensity over the 75% of the maximal cardiac frequency was followed by non-significant changes of malonyldialdehyde, assayed as a marker of lipid peroxidation, and by an increase of erythrocyte catalase and plasma and erythrocyte glutathione peroxidase after the test. These findings suggest that antioxidant response is broadly versatile and adaptable, and that physical activity may prevent extended cellular damage with consequent flogosis. Hence, controlled physical exercise may contribute to protect target organs, including cardiovascular systems, against oxidative stress.
Clinical and Experimental Hypertension 12/2008; 30(8):776-84. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Control of blood pressure protects against the development of cerebrovascular lesions, stroke, and vascular dementia (VaD). Cerebrovascular disease is increasingly recognized as a cause of cognitive impairment and dementia primarily in the elderly. Nicardipine is a dihydropyridine-type calcium channel blocker (CCB) with a peculiar cerebrovascular profile developed approximately 30 years ago. This study has reviewed the main controlled clinical studies investigating the use of nicardipine in pathologies associated with cerebrovascular injury, such as subarachnoid haemorrhage (SAH), acute stroke, and VaD. SAH is a main cerebrovascular indication of CCBs. In this indication, CCBs prevent vasospasm and improve clinical outcomes. Nimodipine represents the CCB more investigated in this indication. Former studies did not demonstrate a clear advantage of nicardipine versus nimodipine in SAH. A more recent approach using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits, and improved clinical outcome after severe SAH. Controlled trials have shown the effectiveness of the drug in preventing stroke. Increasing evidence suggests some benefit of some CCBs in VaD or mixed degenerative and vascular dementia. In this setting, nicardipine has been investigated in approximately 6,000 patients, with an improvement of cognitive deterioration in more than 60% of patients treated. The pronounced anti-hypertensive activity of nicardipine and its safety and effectiveness in cognitive domain suggest its reconsideration in the treatment of cognitive impairment of vascular origin as well as for reducing the risk of recurrent stroke in patients at high risk of it.
Clinical and Experimental Hypertension 12/2008; 30(8):808-26. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The localization of dopamine stores and the expression and localization of vesicular monoamine transporter (VMAT) type-1 and 2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat thymus and spleen by immunohistochemical, immunochemical techniques and by RT-PCR. In the thymus dopamine immunoreactivity was developed in the cortico-medullary junction and in the medulla, but not in the thymic cortex. In the spleen, dopamine stores were found in reticular structures in the white pulp border and in the white pulp, but not in the red one. Both thymus and spleen expressed VMAT-1 and VMAT-2 immunoreactivity as well as dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity. Immunohistochemistry revealed VMAT-1, VMAT-2 and dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity primarily in the thymic cortical-medulla transitional zone and to a lesser extent in the medulla but not in the cortex. In the spleen, VMAT-1, VMAT-2 and dopamine D1, D2, D3, D4 and D5 receptor immunoreactivity was located primarily in the white pulp border and to a lesser extent in the white pulp. These findings indicate that both thymus and spleen express a dopaminergic system characterized by the presence of dopamine, vesicular monoamine transporters and the five subtypes of dopamine receptors. The presence of these dopaminergic markers suggests that dopamine likely originating from immune cells and/or from sympathetic neuroeffector plexus is released in the lymphoid microenvironment. Based on the microanatomical localization of dopaminergic markers investigated, a role of dopamine in maturation and selection of lymphocytes and activation of immune responses is suggested.
Journal of Neuroimmunology 12/2008; 206(1-2):5-13. · 2.96 Impact Factor
