Biomedical subjects

M Sabbatini

Publications and source records attributed to M Sabbatini.

At least 19 recordsLinked to original sources

PubMed2006

Endocrine dysfunction in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is a genetic disorder caused by lysosomal alpha-galactosidase-A deficiency and is characterized by the systemic accumulation of globotriaosylceramide. All endocrine glands are susceptible to globotriaosylceramide accumulation because of their high vascularization and low cellular proliferation rate. Nevertheless, this endocrine system has never been investigated in detail. OBJECTIVE: We aimed to investigate the function and morphology of the endocrine glands in FD. PATIENTS: The thyroid, gonadal, adrenal, and GH/IGF-I axes were evaluated in 18 FD patients (nine females and nine males, aged 21-64 yr) and 18 sex- and age-matched healthy subjects. STUDY DESIGN: We conducted an observational, analytical, open, prospective study. INTERVENTIONS: Ten of the 18 patients received enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase-A (agalsidase beta) at a dose of 1 mg/kg body weight every 2 wk. RESULTS: FD patients had higher baseline TSH levels than controls (P < 0.01). Three subjects were diagnosed with an early stage of subclinical primary hypothyroidism associated with negative antithyroid antibodies. A history of menses abnormalities, miscarriage, or assisted delivery was found in 89% of FD women. Asthenozoospermia, oligozoospermia, or both were found in all FD men through seminal fluid analysis. FD patients had significantly higher circulating ACTH and lower cortisol levels than controls (P < 0.05). In patients under ERT, a suboptimal cortisol response to the 250-microg ACTH test was found in 10%, and the ACTH-stimulated cortisol peak was significantly correlated to the health status profile (P < 0.05). CONCLUSION: A variety of latent endocrine dysfunctions, including life-threatening conditions, occur in patients with FD. Endocrine dysfunctions are also present in patients already receiving ERT and are in part related to their persistent poor quality of life. An endocrine work-up should be recommended in all FD patients. Adequate monitoring and hormonal therapy, when required, have to be performed in cases of subclinical endocrine dysfunction to avoid life-threatening events.

Adrenal Gland Diseases↗

PubMed2005

Prevalence of hepatitis C virus infection in different population groups in southern Italy.

BACKGROUND: A cross-sectional investigation was carried out between 2000 and 2002 to assess the prevalence of hepatitis C virus infection (HCV) in Naples, southern Italy. PATIENTS AND METHODS: Five groups of individuals were investigated, two at low risk and three at high risk for HCV infection. Blood sample sera were collected among 5,391 individuals (4,059 men and 1,332 women): 1,972 general practitioner (GP) patients and 781 employees of the National Cancer Institute (NCI) of Naples (low-risk groups); 524 male prisoners, 1,436 intravenous drug users (IDUs) and 678 hemodialysis patients (high-risk groups). RESULTS: Overall HCV seropositivity rates ranged from 6.4% among employees of the NCI to 37.4% among male prisoners. HCV infection tended to generally increase with age, but in IDUs and in male prisoners the upward trend leveled off at 50 years of age. As compared to GP patients, IDUs (both sexes) and male prisoners had a nearly 6-fold increased risk of HCV infection, while HCV was nearly 3-fold more common among hemodialysis patients. Employees of NCI were at reduced risk of HCV infection, particularly women (odds ratio = 0.3). CONCLUSION: The study findings confirmed the high risk for HCV infection in IDUs and identified other population groups in southern Italy that should be offered HCV screening and counselling given the severe implications of HCV infection on health.

Adolescent↗

PubMed2004

The pattern of c-Fos immunoreactivity in the hindbrain of the rat following stomach distension.

It has been previously shown that the walls of the stomach contain vagal and splanchnic afferents, connected to low and high threshold (LT and HT) gastric receptors, that convey physiological and noxious information to areas of the hindbrain involved mainly in the control of gastrointestinal function. Because distension of the stomach also reflexly increases the sympathetic drive to the cardiovascular system, the present study was planned to examine the pattern of activation of all nuclei encountered throughout the hindbrain in response to gastric distension. In anaesthetized rats, the stimulus was controlled by employing different transmural pressures and frequencies of distension, and c-Fos immunohistochemistry was used to characterize neuronal activation. Low intensity stimulation induced c-Fos expression in the cranial part of nucleus of solitary tract (NTS), the nucleus ambiguus (NA), the lateral reticular area (LRt) and the ventrolateral medulla (RVL/CVL). At low frequency of stimulation c-Fos positive nuclei (p.n.) were found in NTS only. At high frequency of stimulation an increase in c-Fos immunoreactivity was found. High intensity stimulation induced c-Fos expression in area postrema (AP), the lateral vestibular nucleus (LVe) and the caudal part of the NTS. At low frequency, only the number of c-Fos p.n. was increased. Increasing the frequency of stimulation induced c-Fos expression in further nuclei such as the parabrachial nucleus (PBN), the inferior olive subnuclei (IOn), the oral part of spinal trigeminal nucleus (Sp5O) and locus coeruleus (LC). At higher frequencies c-Fos immunoreactivity decreased in NTS and LRt, disappeared in VLM and increased in NA. Thus stomach distension activated several neuronal excitatory and inhibitory circuits that are involved in the control of gastrointestinal function as well as in cardiovascular, respiratory and pain regulation. The differences in c-Fos immunoreactivity induced by changing the distension patterns suggested interactions between groups of vagal and splanchnic afferents.

Animals↗

PubMed2004

Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.

Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness.

Analysis of Variance↗

PubMed2003

Fluoroapatite glass-ceramic coating on alumina: surface behavior with biological fluids.

The results of a surface analysis performed on a fluoroapatite-based glass ceramic (SAF) also coating a full-density alpha-alumina substrate (SAF-alumina coating) are presented. These two materials have also been evaluated after soaking in simulated body fluid to understand their ability to induce hydroxyapatite growth on them. Aiming to understand the fluoroapatite glass-ceramic interaction with some plasma proteins, in the second part of this study, fibronectin, albumin, immunoglobulin G, IgA, and complement factor C3c SAF binding have been evaluated; surface activity on complement activation has also been quantified. SAF-alumina coating provides good sites for the nucleation and growth of an apatite layer, equivalent to the mineral component of bone and binds preferentially plasma fibronectin, which is well known to enhance cell adhesion and spreading. Moreover, SAF-alumina coating reduces alumina complement activation directly or via reduced IgA binding. Alumina was shown to bind the same C3 fragments as Zymosan, used as complement activating control, and to induce increased levels of serum soluble iC3b and Bb. A mechanical resistant material with enhanced bioactivity, bone integration, and reduced inflammatory potential respect to alumina has been obtained.

Adsorption↗

PubMed2003

Fibroblast apoptosis and caspase-8 activation in aseptic loosening.

The presence of apoptosis has been investigated in the interface membranes collected during revision surgery of loosened total hip joint arthroplasty (THAs). Terminal deoxyrobonucleotidyl transferase (TdT) assay for apoptotic DNA fragmentation quantification revealed a statistically significant presence of apoptosis in aseptic samples, obtained from both cementless (2.37+/-0.6%) and cemented (12.01+/-1%) prosthesis compared to septic samples where apoptosis was almost absent. Activated caspase-8 immunostaining was almost undetectable in septic samples, while in the aseptic samples active caspase-8 was present weakly in the cementless samples (1.35+/-0.22%) and strongly in the cemented ones (9.0+/-0.40%). The caspase-8 cytoplasmatic staining allowed the morphological recognition of positive cells both as fibroblast-like and immunocompetent cells. In aseptic cemented samples fibroblast-like cells were the most represented subpopulation in the caspase-8 positive population scored (76.6%) compared to the immunocompetent cells (23.4%). Caspase-8 activation is an upstream event in the apoptotic pathway triggered by the activation of cytokines receptors such as TNF-alpha receptor 1 (TNFR-1), and the presence of caspase-8 activation in fibroblast-like cells in the aseptic interface membranes of THAs suggests a possible TNF-alpha dependent apoptosis.

Apoptosis↗

PubMed2003

Surface oxidation of UHMWPE for orthopedic use increases apoptosis and necrosis in human granulocytes.

Ultra high molecular weight polyethylene (UHMWPE) used in orthopedic prosthesis is often sterilized with gamma-rays and the subsequent oxidation was suggested to favor the in vivo wear. UHMWPE debries produced by wearing trigger an inflammatory response that can led to the implant failure. To explore direct effects of UHMWPE oxidation on immunocompetent cells and their possible role in the prosthesis failure, peripheral blood cells (PBCs) have been grown for 24 and 48 h onto plastic (Ct), UHMWPE (PE) and heat oxidized UHMWPE (PEOx) discs. PBCs necrosis and apoptosis were assessed in flow cytometry using propidium iodide staining. After 24 h, no statistically significant differences were observed in the amount of apoptotic and necrotic cells between Ct, PE and PEOx samples while, after 48 h, both necrotic and apoptotic cells were strongly increased in PEOx samples where also the granulocytes population appeared strongly reduced (6.3+/-1.1%) compared to PE (10.5+/-1.5%) and Ct (15.1+/-0.9%) samples. We conclude that surface oxidation may interfere with prosthetic failure and/or integration via granulocytes modulation.

Journal Article↗

PubMed2003

Fourier transform infrared spectroscopy application to vascular biology: comparative analysis of human internal mammary artery and saphenous vein wall.

Saphenous vein (SV) and internal mammary artery (IMA) are used for aorto-coronary bypass grafting. IMA is considered to be the graft of choice for coronary revascularization having a long-term patency compared to SV. The aim of this study is to investigate the structure of vascular wall using a new technical approach. We analysed the chemical composition of vessel wall layers (total lipid, lipid ester and protein) of 25 vascular segments (19 SV and 6 IMA) using Fourier transform infrared spectroscopy (FTIR). FTIR analysis showed that in intima layer lipid ester and protein concentration (expressed as arbitrary units) was significantly higher in SV (lipid ester = 0.020 +/- 0.002; protein = 0.449 +/- 0.022) than in IMA (lipid ester = 0.014 +/- 0.002; protein = 0.342 +/- 0.032). Moreover, the percentage of lipid ester on total lipid was significantly higher in SV (intima = 54.7 +/- 2.9%; media = 78.4 +/- 4.9%; adventitia = 83.9 +/- 8.3%) wall layers compared to IMA ones (intima = 37.3 +/- 4.9%; media = 45.4 +/- 3.8; adventitia = 57.1 +/- 4.8). These data suggest that a different chemical composition of wall layers could also be responsible for the morphological modifications observed in SV after grafting.

Aged↗

PubMed2001

Effect of 17-beta estradiol and epidermal growth factor on DNA and RNA labeling in astroglial cells during development, maturation and differentiation in culture.

Growth factors stimulate astroglial and neuronal proliferation and differentiation in culture. Estrogens markedly influence astroglia, and are key factors participating in neurodegeneration. The aim of the present study was to investigate interactions between estradiol (E2) and epidermal growth factor (EGF) during astroglia development, maturation and differentiation in culture. DNA or RNA labeling in 16 or 40 or 60 days in vitro (DIV) astrocyte cultures treated for 24 or 48 h with EGF and/or E2 was evaluated. A significant increase in DNA labeling in 16 DIV astrocyte cultures treated for 24 h with EGF (5 ng/ml) and E2 (1 nM) was found. EGF (5 or 10 ng/ml) addition in the last 24 h in 48 h E2 (1 or 5 nM)-treated astrocyte cultures at 16 DIV caused a slight, but significant increase in DNA labeling. No differences in RNA labeling were observed in 16 DIV astrocyte cultures treated for 24 or 48 h with EGF (5 or 10 ng/ml) in the presence of E(2) (1 or 5 nM). A significant stimulation in DNA labeling was shown in 40 DIV astrocyte cultures treated for 48 h with E2 (1 or 5 nM) in the presence of EGF (5 or 10 ng/ml) added in the last 24 h. In well differentiated astroglial cell cultures (60 DIV), DNA labeling was remarkably increased after 24 h treatment with 1 nM E2 or 5 ng/ml EGF. Co-addition of 1 nM E2 and 5 ng/ml EGF for 24 h reduced [methyl-(3)H]thymidine incorporation, when data are compared to E2- or EGF-treated cultures. Addition of EGF in the presence of E2 for 48 h or only in the last 24 h caused a significant decrease of [methyl-(3)H]thymidine incorporation in comparison with EGF-treated cultures at 60 DIV or with untreated cultures. Treatment of cultures for 24 h with EGF (5 or 10 ng/ml) alone or in combination with E2 (1 or 5 nM) induced a strong increase of RNA labeling in 60 DIV astrocyte cultures. Addition for 48 h of E2 (1 or 5 nM) or EGF (5 or 10 ng/ml) alone or in association stimulated significantly RNA labeling in astrocyte cultures at 60 DIV. When 60 DIV astrocyte cultures were treated for 48 h with E2 (1 or 5 nM) in the presence of EGF (5 or 10 ng/ml) added only in the last 24 h, a potentiating effect of RNA labeling was observed. The above results suggest that interaction between growth factors and estrogens may contribute to regulate astroglia development, maturation and differentiation.

Astrocytes↗

PubMed2001

Influence of treatment with Ca(2+) antagonists on cerebral vasculature of spontaneously hypertensive rats.

Hypertension is the main cause of stroke that represents the second most common cause of death in the industrialized world and a leading cause of inability of the elderly. Lowering blood pressure reduces cerebrovascular morbidity and mortality, but it is still controversial if blood pressure should be lowered in elderly individuals with concomitant cerebrovascular disease. The present study has analyzed comparatively the effect of treatment with the dihydropyridine-type Ca(2+) channel blockers lercanidipine, manidipine and nimodipine and with the non dihydropyridine-type vasodilator hydralazine on hypertension-dependent cerebrovascular changes in spontaneously hypertensive rats (SHR). Analysis included medium and small sized pial arteries and intracerebral arteries of frontal cortex, hippocampus, striatum, and cerebellum. In control SHR, systolic pressure (SBP) values were significantly higher in comparison with WKY rats. Pharmacological treatment significantly decreased SBP values, with nimodipine reducing only moderately SBP. In control SHR, thickening of arterial wall accompanied by luminal narrowing with consequent increase of the wall-to-lumen ratio occurred both in pial and intracerebral arteries. Dihydropyridine-type Ca(2+) antagonists and to a lesser extent hydralazine countered these morphological alterations. Lercanidipine displayed a particular activity on small sized intraparenchymal brain arteries, where it was more effective than other compounds tested. This activity of lercanidipine on small-sized intracerebral arteries might represent an interesting property for the treatment of hypertensive brain damage with concomitant ischemia.

Animals↗

PubMed2001

Microanatomical changes of intracerebral arteries in spontaneously hypertensive rats: a model of cerebrovascular disease of the elderly.

Changes occurring in intracerebral arteries of 24-week-old spontaneously hypertensive rats (SHR) compared with age-matched normotensive Wistar-Kyoto (WKY) rats were assessed using microanatomical techniques associated with image analysis. Morphometric parameters investigated included arterial diameter, lumen area, wall area, and wall-to-lumen ratio. Intracerebral arteries (lumen diameter>46 microm) and arterioles (lumen diameter 46-10 microm) of frontal cortex, striatum, and hippocampus were examined. In frontal cortex of SHR arterial wall hypertrophy and luminal narrowing were observed. In striatum, an increase of wall area not accompanied by luminal narrowing predominates resulting in arterial hypertrophy without vasoconstriction. In hippocampal arteries of SHR, luminal narrowing, without changes of wall area was found indicating the occurrence of remodeling. In brain areas investigated, hypertensive changes affected primarily arterioles. The demonstration of a sensitivity of intracerebral arteries to hypertension suggests that changes of these vessels may represent a cause of brain structural alterations occurring in hypertension. The specificity of alterations occurring in intracerebral arteries of brain areas investigated may account for the different localization of cerebral lesions in cerebrovascular disease. The possibility that microanatomical changes developed in intracerebral arteries of SHR may represent a model of cerebrovascular disease of the elderly is discussed.

Aging↗

PubMed2001

Age-related changes of dopamine receptors in the rat hippocampus: a light microscope autoradiography study.

Hippocampus is a brain region involved in learning and memory and is particularly sensitive to ageing. It is supplied with a dopaminergic innervation arising from the midbrain, which is part of the mesolimbic dopaminergic pathway. Dysfunction of the dopaminergic mesolimbic system is probably involved in the pathophysiology of psychosis and behavioural disturbances occurring in the elderly. The present study was designed to assess the density and localisation of dopamine D1- and D2-like receptor subtypes in the hippocampus of male Sprague-Dawley rats aged 3 months (young), 12 months (adult) and 24 months (old). Dopamine D1-like receptors, labelled by [3H]-SCH 23390, in young rats displayed a dentate gyrus-CA1 subfield gradient. The expression was increased in the cell body of dentate gyrus, CA4 and CA3 subfield of old rats compared to younger cohorts, as well as in the neuropil of dentate gyrus. A decreased density of dopamine D1-like receptors was found in the stratum oriens of CA1 and CA3 subfields. Dopamine D2-like receptors, labelled using [3H]-spiperone as radioligand, were expressed rather homogeneously throughout different subfields of the hippocampus. In old rats, the density of dopamine D2-like receptors was decreased in the dentate gyrus, unchanged in the CA4 and CA1 subfields and increased in the CA3 subfield. The above results indicate the occurrence of inhomogeneous changes in the density of dopamine D1- and D2-like receptors in specific portions of hippocampus of old rats. These findings support the hypothesis of an involvement of dopaminergic system in behavioural abnormalities or psychosis occurring in ageing.

Aging↗

PubMed2001

Hypertensive brain damage: comparative evaluation of protective effect of treatment with dihydropyridine derivatives in spontaneously hypertensive rats.

Hypertension is the main risk factor for cerebrovascular disease including vascular dementia and control of blood pressure might protect from lesions causing cognitive impairment. The influence of anti-hypertensive treatment on hypertensive brain damage was assessed in spontaneously hypertensive rats (SHR). SHR and age-matched normotensive Wistar Kyoto (WKY) rats were treated from the 14-26th week of age with the dihydropyridine-type Ca2+ channel blockers lercanidipine, manidipine and nimodipine and as a reference with the non-dihydropyridine-type vasodilator hydralazine. Volume of brain areas, number of nerve cells and glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes and neurofilament 200 kDa immunoreactivity were investigated in frontal and occipital cortex and in hippocampus. In control SHR, systolic blood pressure (SBP) was significantly higher in comparison with WKY rats. Compounds tested decreased to a similar extent SBP values in SHR, with the exception of nimodipine that caused a smaller reduction of SBP compared with other compounds. Decreased volume and number of nerve cells and loss of neurofilament protein immunoreactivity were observed in SHR. GFAP-immunoreactive astrocytes increased in number (hyperplasia) and in size (hypertrophy) in the frontal and occipital cortex of control SHR, and only in number in the hippocampus. Anti-hypertensive treatment countered in part microanatomical changes occurring in SHR. Drugs investigated with the exception of nimodipine exerted an equi-hypotensive effect. In spite of this the best protection was exerted by lercanidipine and, to a lesser extent, by nimodipine. Compared with nimodipine, lercanidipine induced a more effective decrease of SBP. This may represent an advantage in the treatment of hypertension with risk of brain damage.

Animals↗

PubMed2001

Changes of retinal neurons and glial fibrillary acid protein immunoreactive astrocytes in spontaneously hypertensive rats.

OBJECTIVE: The influence of arterial hypertension on retinal neurons and glial fibrillary acid protein (GFAP) immunoreactive astrocytes was investigated in spontaneously hypertensive rats (SHRs). METHODS: The retinas of 4- and 6-month-old SHRs and age-matched Wistar-Kyoto rats (WKY) were investigated. A group of SHRs, treated from 4 to 6 months with the hypotensive drug hydralazine, was also examined. Microanatomical and immunohistochemical techniques associated with image analysis and the terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) technique for apoptosis or necrosis were used, as well as astrocyte molecular biology (Western blot) techniques. RESULTS: In 4-month-old SHR and WKY rats, retinal morphology and the number of retinal neurons and of GFAP-immunoreactive astrocytes were similar, with the exception of the occurrence of 1% of TUNEL-positive ganglionic neurons in SHRs. In 6-month-old SHRs a decrease of retinal volume and of the number of ganglionic neurons and photoreceptors was observed, compared with age-matched normotensive WKY rats or younger SHR and WKY rats. Two per cent of ganglionic neurons and 5% of photoreceptors were also TUNEL positive. In 6-month-old SHRs, hypertrophic perivascular GFAP-immunoreactive astrocytes were found, whereas their number was unchanged compared to younger cohorts or WKY rats. An increased expression of GFAP was also noticeable in SHRs by Western blot analysis. Hypotensive treatment with hydralazine partly countered retinal changes occurring in SHRs. CONCLUSIONS: The occurrence of neuronal and astroglial changes when a stable hypertension was developed, and their sensitivity to antihypertensive treatment, suggest that they may represent a hypertension-related phenomenon.

Animals↗

PubMed2000

Influence of age on L-type Ca2+ channels in the pulmonary artery and vein of spontaneously hypertensive rats.

The influence of age on the density and localization of L-type Ca2+ channels was studied during development of hypertension in the pulmonary artery and vein of spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats by radioligand binding assay and light microscope autoradiography. SHR were examined at 6 weeks (juvenile, pre-hypertensive stage), 12 weeks (young, developing hypertension) and 24 weeks (mature, established hypertension). The dihydropyridine-type Ca2+ antagonist [3H]nicardipine was used as a radioligand. It was bound specifically to sections of rat pulmonary artery and vein. Dissociation constant (Kd) values were similar in WKY rats and SHR, whereas maximum density of binding sites (Bmax) values increased in SHR in comparison with WKY rats. This increase was noticeable from the pre-hypertensive phase. The pharmacological profile of [3H]nicardipine binding was similar in different age groups of either normotensive and hypertensive rats. Quantitative analysis of autoradiographs from SHR revealed a progressive increase of silver grains in smooth muscle of tunica media and to a lesser extent in the adventitia of pulmonary artery but not of pulmonary vein from pre-hypertensive stage to developing hypertension. No further changes were observed in established hypertension. The above data indicate that the density of L-type Ca2+ channels of pulmonary arteries is increased in SHR. This augmentation after the pre-hypertensive phase suggests the occurrence of dysregulation of Ca2+ handling in the pulmonary vasculature of developing SHR.

Aging↗

PubMed2000

Acute effects of rapamycin on glomerular dynamics: a micropuncture study in the rat.

The acute effects of cyclosporin (CsA, 20 mg(kg i.v.) and rapamycin (RAPA, 5 mg(kg i.v.) on glomerular dynamics were separately investigated by renal micropuncture in two groups of intact rats (group CsA and RAPA, respectively) and compared with vehicle-treated rats, used as controls (group CON). Left kidney glomerular filtration rate (GFR) was decreased by CSA (-35% vs. CON, P<0.05), but was not affected by RAPA (-14% vs. CON, NS), whereas the single-nephron GFR (SNGFR) was significantly decreased in both groups (-40% in CsA, P<0.01 and -26% in RAPA, P<0.05 vs. CON). In both groups glomerular plasma flow (GPF) was significantly reduced vs. CON (CsA: -48%, and RAPA: -25%) due to the increase in both afferent (Ra) and efferent (Re) glomerular resistances: group CSA showed a prevalent rise in Re (+98% vs. CON, P<0.001) than in Ra (+66%, P<0.001); in group RAPA the increment was modest and similar in Ra and Re (+33 and +32%, respectively, NS versus CON). A further group of rats was studied in which L-Arginine (ARG), the precursor of nitric oxide (NO), was administered (2.5 mg/Kg/min iv) with RAPA (group ARG). ARG limited the rise in Ra and Re, thereby preserving GPF; nevertheless, SNGFR remained low (-26% vs. CON, P<0.05) due to the decrease in the effective filtration pressure (-26% vs. CON). These data demonstrate that: (1) CsA is nephrotoxic at immunosuppressive doses; (2) RAPA, even at huge doses, has marginal effects on renal and glomerular dynamics; (3) the ARG-NO pathway is only partially involved in the vasoconstriction of superficial nephrons after RAPA administration.

Animals↗

PubMed2000

Retracted: The hippocampus in spontaneously hypertensive rats: a quantitative microanatomical study.

The influence of hypertension on the morphology of hippocampus was assessed in spontaneously hypertensive rats of two, four and six months and in age-matched normotensive Wistar-Kyoto rats. Values of systolic pressure were slightly increased in two-month-old spontaneously hypertensive rats in comparison with age-matched Wistar-Kyoto rats and augmented progressively with age in spontaneously hypertensive rats. No microanatomical changes were observed in the hippocampus of spontaneously hypertensive rats of two months in comparison with age-matched Wistar-Kyoto rats, whereas a decrease of white matter volume was observed in the CA(1) subfield and in the dentate gyrus of four-month-old spontaneously hypertensive rats. In the hippocampus of six-month-old spontaneously hypertensive rats a reduction of grey matter volume both in the CA(1) subfield and in the dentate gyrus, a loss of neurons affecting to a greater extent the CA(1) subfield and an increase of glial fibrillary acid protein-immunoreactive astrocytes was found. The occurrence of apoptosis and/or necrosis identified using the terminal deoxyribonucleotidyl transferase-mediated biotin-16-dUTP nick end labelling technique was also observed in the CA(1) subfield and to a lesser extent in the dentate gyrus. The only change noticeable in the CA(3) subfield of six-month-old spontaneously hypertensive rats was a slight increase in the number of glial fibrillary acid protein-immunoreactive astrocytes. These findings indicate the occurrence of neuronal loss and of astrocyte changes in the hippocampus of spontaneously hypertensive rats of six months, being the CA(1) subfield the area most affected. The relevance of these neurodegenerative changes in hypertension and the possible occurrence of apoptosis and/or necrosis as expression of hypertensive brain damage is discussed.

Animals↗

PubMed2000

Effect of calcium antagonists on glomerular arterioles in spontaneously hypertensive rats.

Through the use of microanatomic techniques, we investigated the effects of treatment with some dihydropyridine-type calcium antagonists (CAs) (ie, lercanidipine, manidipine, and nicardipine) and with the nondihydropyridine-type vasodilator hydralazine on hypertension-dependent glomerular injury and on the morphology of afferent and efferent arterioles in spontaneously hypertensive rats (SHR). Fourteen-week-old male SHR and age-matched normotensive Wistar-Kyoto rats were left untreated (control groups). Four additional groups of 14-week-old SHR were treated for 12 weeks with daily oral doses of 2.5 mg/kg lercanidipine, 5 mg/kg manidipine, 3 mg/kg nicardipine, or 10 mg/kg hydralazine. These treatments decreased systolic blood pressure values to a similar extent in SHR. Signs of glomerular injury, as characterized by glomerulosclerosis, hypertrophy, and an increased number of mesangial cells, were observed in control SHR. The treatment with CAs improved glomerular morphology and decreased the number of mesangial cells. Lercanidipine and manidipine were more effective than nicardipine in countering glomerular injury. In the SHR, both afferent and efferent arterioles revealed luminal narrowing, accompanied by increased wall thickness in efferent arterioles. The dihydropyridine-type derivatives that were tested decreased the luminal narrowing of afferent arterioles. Lercanidipine and manidipine countered the luminal narrowing of efferent arterioles. Hydralazine had no effect on hypertension-dependent glomerular injury or vascular changes. The present data indicate that lercanidipine and manidipine vasodilate afferent and efferent arterioles in SHR. A vasodilatory activity on efferent arteriole, which is not induced by the majority of CAs, may represent an useful property in the treatment of hypertension complicated by renal disease.

Albuminuria↗