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Influence of the drugs for membrane excitability modification on the excitation caused by achatin-I.

1. The pneumatic pressure ejection of achatin-I (Gly-D-Phe-L-Ala-L-Asp), an endogenous tetrapeptide having a D-phenylalanine residue, produced an inward current (Iin) in an identifiable giant neuron, PON (periodically oscillating neuron), of an African giant snail, Achatina fulica Férussac. The influence of the drugs for membrane excitability modification, applied by perfusion, on the PON excitation caused by achatin-I was examined under voltage clamp. 2. The four channel blocking drugs, tetrodotoxin (TTX), tetraethylammonium chloride (TEA), verapamil and picrotoxin, at 10(-4) M did not affect significantly the PON excitation caused by the peptide. 3. N-beta-phenylpropionyl-L-tyrosine (BPLT), a membrane hyperpolarizant, at 10(-6) M and concanavalin A (Con A), which altered the response to L-glutamate, at 100 micrograms/ml-1 were considered to hardly influence the PON excitation caused by achatin-I.

Amino Acid Sequence↗

Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on paraoxonase and platelet-activating factor acetylhydrolase in human plasma and tissue fluid.

We have previously shown that intravenous apolipoprotein (apo) A-I/phosphatidylcholine (apo A-I/PC) discs increase plasma high-density lipoprotein (HDL) concentration in humans. We have now studied the associated changes in two enzymes, paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH) that are carried in whole or in part by HDLs, and are thought to influence atherogenesis by hydrolyzing oxidized phospholipids in lipoproteins. Apo A-I/PC discs (40 mg/kg over 4 h) were infused into eight healthy males. Although plasma apo A-I and HDL cholesterol increased on average by 178 and 158%, respectively, plasma total PON and total PAF-AH concentrations did not rise. By the end of the infusion, HDL-associated PAF-AH had increased by 0.56 +/- 0.14 microg/mL (mean +/- S.D., P < 0.01), and nonHDL-associated PAF-AH had decreased by 0.84 +/- 0.11 microg/mL (P < 0.05). These changes were accompanied by an increase in the HDL-associated PAF-AH/apo A-I ratio from 0.19 to 0.35 (P < 0.05), and by a decrease in the nonHDL-associated PAF-AH/apo B ratio from 2.1 to 1.4 (P < 0.05). No changes in PON or PAF-AH concentrations were detected in prenodal lymph (tissue fluid), collected continuously from the leg. Our results show that the total concentrations of PON and PAF-AH in plasma are uninfluenced by plasma HDL concentration. PAF-AH transfers readily between HDLs and LDLs in vivo, and its distribution between them is determined partly by their relative concentrations and partly by HDL composition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Regional expression of NO synthase, NAD(P)H oxidase and superoxide dismutase in the rat brain.

Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) contributes to regulation of cerebral circulation, whereas that produced by neuronal NOS (nNOS) participates in the regulation of brain function. In particular, NO plays an important role in modulation of sympathetic activity and hence central regulation of arterial pressure. Superoxide derived from NAD(P)H oxidase avidly reacts with and inactivates NO and, thereby, modulates its bioavailability. Calmodulin (CM) is required for activation of NOS and soluble guanylate cyclase (sGC) serves as a NO receptor. Superoxide is dismutated to H2O2 by superoxide dismutase (SOD) and H2O2 is converted to H2O by catalase or glutathione peroxidase (GPX). Given the importance of NO in the regulation of brain perfusion and function, we undertook the present study to determine the relative expressions of immunodetectable nNOS, eNOS, CM, sGC, NAD(P)H oxidase and SOD by Western analysis in different regions of the normal rat brain. nNOS was abundantly expressed in the pons cerebellum and hypothalamus and less so in the cortex and medulla. sGC abundance was highest in the hypothalamus and pons, and lowest in the cerebellum and medulla. eNOS and calmodulin were equally abundant in all regions. NAD(P)H oxide was most abundant in the pons compared to other regions. Cytoplasmic SOD was equally distributed among different regions but catalase and GPX were more abundant in pons, hypothalamus and medulla and less so in the cortex and cerebellum. Thus, the study documented regional distributions of NOS, NAD(P)H oxidase, antioxidant enzymes, sGC and calmodulin which collectively regulate production and biological activities of NO and superoxide, the two important small molecular size signaling molecules.

Animals↗

Brainstem 1H-MR spectroscopy in patients with Parkinson's disease with REM sleep behavior disorder and IPD patients without dream enactment behavior.

OBJECTIVES: The objective of our study was to evaluate brainstem involvement by 1H-MR spectroscopy (1H-MRS) method in patients with idiopathic Parkinson's disease (IPD) with REM sleep behavior disorder (RBD) and IPD without dream enactment behavior. PATIENTS AND METHODS: We prospectively studied 12 IPD (3 females, 9 males) with a clinically and electrophysiologically confirmed RBD and 12 IPD (3 females, 9 males) patients without dream enactment behavior followed in Outpatient Clinics for Movement Disorders of Department of Neurology, Haseki Hospital. Using long and short TE single voxel 1H-MRS directed at ventral and dorsal pons, long TE NAA/Cr, Ch/Cr and short TE NAA/Cr, Ch/Cr, MI/Cr values of both groups were compared. RESULTS: Although no difference was found between groups with RBD and IPD without dream enactment behavior in demographic characteristics, duration of disease, mean levodopa dosage and duration of levodopa use, all UPDRS scores (total, motor and cognitive) were worse in RBD group (p<0.05). There was no statistically significant difference in long TE NAA/Cr, Ch/Cr and short TE NAA/Cr, Ch/Cr, MI/Cr values obtained in both groups (p>0.05). CONCLUSION: 1H-MRS does not detect marked metabolic differences in the pons in subjects with IPD with RBD and IPD without dream enactment behavior. This finding suggests either that present methodologies are not sensitive to detect subtle metabolic changes in the pons of subjects with RBD or that the primary lesion of RBD exists in other REM sleep-related brain regions beyond the pons such as the substantia nigra, the basal ganglia or the limbic system.

Aged↗

Lethal giant larvae controls the localization of notch-signaling regulators numb, neuralized, and Sanpodo in Drosophila sensory-organ precursor cells.

Asymmetric distribution of fate determinants is a fundamental mechanism underlying the acquisition of distinct cell fates during asymmetric division. In Drosophila neuroblasts, the apical DmPar6/DaPKC complex inhibits Lethal giant larvae (Lgl) to promote the basal localization of fate determinants. In contrast, in the sensory precursor (pI) cells that divide asymmetrically with a planar polarity, Lgl inhibits Notch signaling in the anterior pI daughter cell, pIIb, by a yet-unknown mechanism. We show here that Lgl promotes the cortical recruitment of Partner of Numb (Pon) and regulates the asymmetric distribution of the fate determinants Numb and Neuralized during the pI cell division. Analysis of Pon-GFP and Histone2B-mRFP distribution in two-color movies confirmed that Lgl regulates Pon localization. Moreover, posterior DaPKC restricts Lgl function to the anterior cortex at mitosis. Thus, Lgl functions similarly in neuroblasts and in pI cells. We also show that Lgl promotes the acquisition of the pIIb cell fate by inhibiting the plasma membrane localization of Sanpodo and thereby preventing the activation of Notch signaling in the anterior pI daughter cell. Thus, Lgl regulates cell fate by controlling Pon cortical localization, asymmetric localization of Numb and Neuralized, and plasma-membrane localization of Sandopo.

Animals↗

Plasma markers of endothelial dysfunction in type 2 diabetics.

BACKGROUND: Type 2 diabetes, or non-insulin-dependent diabetes mellitus, represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Atherosclerotic lesions occur in diabetic patients at an earlier age with severe clinical manifestations and poor outcome. Our objective was to investigate the correlation between lipoprotein-associated phospholipase A2 (PLA2-LDL), myeloperoxidase (MPO), and paraoxonase (PON), enzymes implicated in the evolution of endothelial dysfunction associated with type 2 diabetes. METHODS: One hundred diabetic patients [50 without documented coronary artery disease (group 1) and 50 with CVD (group 2)] and 46 healthy controls were investigated for PLA2-LDL, MPO, and PON activities. RESULTS: PLA2-LDL activity was significantly higher in group 2 than in group 1 and among controls. PON activity was lower in group 1 than in controls, reaching the lowest level in group 2. MPO activity was higher in type 2 diabetics than among controls, with similar values in groups 1 and 2. CONCLUSIONS: The evaluation of PLA2-LDL, MPO, and PON activities may improve early diagnosis of CVD in asymptomatic patients with type 2 diabetes and can help to evaluate accelerated atherosclerosis and microvascular disease.

Journal Article↗

HDL capacity to inhibit LDL oxidation in well-trained triathletes.

Physical activity is known to play a cardioprotective role. Nevertheless, a paradox seems to arise when considering that aerobic exercise enhances oxidative stress. In previous works, we showed that free radical formation during physical activity was counteracted by an increase in antioxidant defenses. Low density lipoprotein (LDL) oxidation is a crucial step in atherosclerosis, process that can be inhibited by high density lipoprotein (HDL) through its oxidable components or associated enzymes like paraoxonase (PON) and platelet-activating factor acetylhydrolase (PAF-AH). In this study, we evaluated copper-induced oxidation in isolated LDL and HDL fractions, and the effect of HDL on LDL oxidation in samples from well trained amateur athletes who were participating in an ultra-distance triathlon (n=18) in comparison with healthy sedentary controls (n=18). PON and PAF-AH activities and PON phenotype were also evaluated. The oxidability of isolated lipoproteins, as well as HDL antioxidant capacity, was similar in both groups of subjects. After classification by paraoxonase phenotype, only sportsmen belonging to the QR phenotype showed higher HDL susceptibility to in vitro oxidation (thiobarbituric reactive substances, TBARS) than controls (p<0.05). HDL oxidability exhibited a positive correlation with its triglyceride content (r=0.58; p<0.01). Similarly, HDL capacity to inhibit LDL oxidation was increased in athletes (p<0.05) which was positively associated with HDL oxidability (HDL-TBARS: r=0.55, p<0.005; HDL-lag time: r=0.45, p<0.01; HDL-D max: r=0.35, p<0.05). In conclusion, regular aerobic exercise was associated to a more efficient antioxidant function played by HDL from PON-QR carriers, which could constitute an adaptive response to the increased oxidative stress.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: does paraoxonase genotype play a role?

OBJECTIVES: This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen. METHODS: Thirty women who had undergone hysterectomy+bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion. RESULTS: At the sixth month, a higher TAO activity (p=0.016) and a lower eTBARS (p=0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly (p=0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS (p=0.007), LDL TBARS (p=0.044) and eCAT (p=0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu2+ induced ox-LDLTBARS of QQ subjects (p=0.018 and 0.050) as well as LDL TBARS of QR subjects (p=0.044) showed a significant decrease with estrogen-only treatment. CONCLUSIONS: Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies.

Antioxidants↗

Survival rates through time of hypocretin grafted neurons within their projection site.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, inadvertent transitions from wakefulness to rapid eye movement sleep (so called "sleep-onset REMS period") and cataplexy (sudden bilateral skeletal muscle weakness during waking without impairment of consciousness). This disorder has been recently linked to a loss of hypocretin (HCRT) neurons making narcolepsy a neurodegenerative disease. Neuronal replacement could be used to reverse the symptoms of narcolepsy. Towards this end, we have recently reported that HCRT neurons from rat pups can survive when grafted into the pons of adult rats. Here, we investigate the time-course of survival of grafted HCRT neurons into the pons of adult rats. The HCRT neurons are present only in the lateral hypothalamus, and therefore suspension of cells from this region was derived from 8- to 10-day-old rat pups (donor), and grafted into the pons of adult (60 days old) host rats. Control rats received a transplant that consisted of cells from the cerebellum where no HCRT neurons are present. All adult host rats were sacrificed 1, 3, 6, 9, 12, 24, or 36 days after grafting. Immunohistochemistry was used to identify and count the presence of the HCRT grafted neurons in the target area. The tally of HCRT neurons present in the graft zone 1 day post-grafting was considered to be the baseline. From day 3 to 36 post-transplant there was a steady decline in the number of HCRT neurons. We also noted that on day 36, the HCRT neurons that survived in the pons had morphological features that were similar to mature HCRT neurons in the adult lateral hypothalamus, suggesting that these neurons might be functionally active. Control rats that received grafts of cerebellar tissue did not show HCRT neurons in the target area. These results demonstrate that there is a progressive decline in the number of transplanted neurons, but a significant percentage of HCRT neurons do survive until day 36. This study highlights the potential use of transplants as a therapeutical tool in order to treat narcolepsy.

Animals↗

An immunocytochemical mapping of methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) in the human brainstem.

Using an indirect immunoperoxidase technique, we studied the distribution of immunoreactive fibers and cell bodies containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) in the adult human brainstem. Immunoreactive cell bodies were found in the reticular formation of the medulla oblongata (in which we observed the highest density of immunoreactive cell bodies) and the pons, the solitary nucleus, the hypoglossal nucleus, the medial and spinal vestibular nuclei, the lateral cuneate nucleus, the nucleus prepositus, the central gray of the pons and mesencephalon, the central and pericentral nuclei of the inferior colliculus, the superior colliculus, ventral to the superior olive and in the midline region of the pons and mesencephalon. The highest density of immunoreactive fibers containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) was found in the spinal trigeminal nucleus, the central gray and the reticular formation of the medulla oblongata, pons and mesencephalon, the solitary nucleus, the spinal vestibular nucleus, the dorsal accessory olivary nucleus, the raphe obscurus, the substantia nigra and in the interpeduncular nucleus. The widespread distribution of immunoreactive structures containing methionine-enkephalin-Arg(6)-Gly(7)-Leu(8) in the human brainstem indicates that this neuropeptide might be involved in several physiological mechanisms, acting as a neurotransmitter and/or neuromodulator.

Aged↗

Smoking during early pregnancy affects the expression pattern of both nicotinic and muscarinic acetylcholine receptors in human first trimester brainstem and cerebellum.

Prenatal nicotine exposure is associated with an increased risk of complications during pregnancy and childhood. In this study the expression of nicotinic and muscarinic acetylcholine receptors in first trimester pons, medulla oblongata and cerebellum from abortus (5-12 weeks of gestation) of smoking and nonsmoking women was compared. A significant age-related increase in binding of nicotinic receptor subtype alpha4 was found in both pons and cerebellum only in fetal tissue from non-smoking women, while a similar increase was observed in medulla oblongata from fetuses exposed to smoking. A significant age-related increase in binding of muscarinic receptor subtype m2 was observed in pons from abortus of smoking compared with non-smoking women. The gene expression pattern of both alpha4 and alpha7 nicotinic receptor subunits was changed after smoking in all three regions investigated. Smoking also changed the expression of m1 and 2 muscarinic receptor mRNA in pons, m1 mRNA in cerebellum and the m3 mRNA in medulla oblongata. The findings indicate that early prenatal nicotine exposure affects the normal developmental pattern of the cholinergic system in human fetal brain.

Alkaloids↗

Dissociation of IGF2 and H19 imprinting in human brain.

The human IGF2 and H19 genes are imprinted in most normal tissues. Alterations of genomic imprinting or loss of imprinting (LOI) have been observed in a number of malignant tumors. Although LOI has been linked to tumorigenesis, loss of IGF2 imprinting has also been observed in choroid plexus and leptomeninges in normal mouse brain. We have therefore analyzed the allelic expression of both IGF2 and H19 in human fetal brain and in different regions of human adult brain. In the brains of fetuses of 6-12 weeks gestation, both IGF2 and H19 were transcribed from both parental alleles. In contrast, strictly monoallelic expression of both IGF2 and H19 was observed in all other fetal tissues, suggesting a tissue-specific LOI in the central nervous system. In adult brain, LOI of IGF2 was region-specific. IGF2 was expressed from both parental alleles in the pons, but not in globus palludus, Raphe nucleus and hypothalamus. H19 expression was drastically reduced in adult brain compared to fetal brain, and was detectable only in the pons and globus palludus. In contrast to IGF2, the expression of H19 in adult pons was monoallelic. Examination of IGF2 promoter usage indicated predominant utilization of promoter P3 in all fetal and adult brain tissues. The LOI of IGF2 therefore reflects biallelic expression from the predominant promoter. IGF2 transcripts derived from the less abundant promoter P1, however, showed monoallelic expression in the adult pons. Our results suggest that IGF2 and H19 undergo ontogenetic changes in allelic expression and that there is dissociation of IGF2 and H19 imprinting in both fetal and adult human brain.

Aging↗

Genetic variations of the paraoxonase gene in patients with coronary artery disease.

OBJECTIVES: Paraoxonase (PON) plays an important role in preventing low density lipoprotein (LDL) oxidation and thus may be involved in protection against atherosclerosis. Several studies have suggested that genetic variations of the PON gene are associated with plasma HDL levels and coronary artery disease (CAD). This study was conducted to elucidate the association between three polymorphisms of the PON1 and PON2 genes and Korean patients with CAD. DESIGN AND METHODS: One hundred ninety-one patients with CAD and 113 age-matched normal controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for PON polymorphisms by restriction enzyme digestion. RESULTS: There was linkage disequilibria between each polymorphism pair in the CAD and control groups. The Hsp92II polymorphism at codon 54 of the PON1 gene was positively associated with HDL-cholesterol levels in the control group (p = 0.02). An association between the AlwI polymorphism and HDL-cholesterol level appeared statistically significant in women of the normal group (p = 0.04). In addition, the DdeI and AlwI polymorphisms were positively associated with HDL (p = 0.02) and LDL (p = 0.03) levels in men of the CAD group, respectively. CONCLUSIONS: Our study suggested a gene-gene interaction between the PON1 and PON2 polymorphisms for CAD risk. However, we could not exclude the possibility that these polymorphisms may have linkage disequilibrium with a tightly linked PON3 locus or significant atherosclerotic alleles of nearby genes. Family studies may, therefore, help to confirm the role of the PON polymorphism for CAD risk.

Adult↗

Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity in Iranian subjects.

To determine the association of serum apolipoprotein (apo) A-I and B concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated enzyme activity with angiographically determined coronary artery disease (CAD) in Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects, 251 subjects aged 30-70 years, who underwent their first coronary angiography were matched and randomly assigned into three groups: CAD(+)DM(+), CAD(+)DM(-), and CAD(-)DM(-) (control). Stenosis of > or =50% in one or more coronary arteries was classified as CAD(+). CAD(-) was defined as a maximum stenosis of 10% in any coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein concentrations were measured in a fasting serum sample by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate. Information concerning non-lipid risk factors were collected by questionnaires. No significant difference was observed in HDL-C, LDL-C, apo A-I, and PON/arylesterase activity between the study groups. The values of TC (213+/-38 vs 196+/-45, P<0.05), TGs (209+/-187 vs 151+/-113, P<0.01), apo B (99+/-22 vs 96+/-24, P<0.0001), TC/HDL-C (4.8+/-1.5 vs 4.0+/-1.3, P<0.001) and LDL-C/HDL-C (2.9+/-1.1 vs 2.4+/-1.1, P<0.05) were higher and apo A-I/B (1.7+/-0.4 vs 2.0+/-0.6, P<0.01) was lower in CAD(+)DM(+) patients than in control subjects. In CAD(+)DM(-) group, only the level of apo B (96+/-24 vs 85+/-18, P<0.01), and the ratio of apo A-I/B (1.8+/-0.4 vs 2.0+/-0.6, P<0.01), were significantly higher than those of control group. On multiple logistic regression analysis, the best markers for discrimination between CAD(+) groups and CAD(-) control subjects were the ratio of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest that in Iranian diabetic and non-diabetic patients with CAD the concentration of apolipoproteins are better markers than traditional lipid parameters in discriminating between CAD(+) and CAD(-) subjects. Lack of significant difference in PON activity between CAD patients and CAD(-) controls supports the concept of interethnic variability in PON polymorphism and unimodal distribution of its activity in non-Europid populations observed in other studies.

Apolipoprotein A-I↗

Lack of association between carotid intima-media thickness and paraoxonase gene polymorphism in non-insulin dependent diabetes mellitus.

Paraoxonase (PON) is an HDL-bound enzyme capable of hydrolyzing lipid peroxides and believed to be in part responsible for the protective effect of HDL against LDL oxidation. Its activity is mainly determined by a gene polymorphism of the PON 1 gene (Glu-Arg 192). Low activity has been related to an elevated incidence of myocardial infarction. In several case-control studies, however, the high activity B allele is paradoxically more prevalent in patients. We have re-investigated this relationship, using carotid intima-media thickness (IMT) as a surrogate continuous variable for macroangiopathy. Genotypes were determined in 197 non insulin-dependent diabetic patients (HbAlc 8.8+/-0.15%, BMI 28.3+/-0.36). IMT, measured by high resolution mode B ultrasound, was the same for all genotypes (AA: 0.83+/-.013, AB 0.82+/-.017 and BB: 0.81+/-.034 mm). Bearers of the B allele displayed higher Lp(a) concentration (AA: 197+/-28, AB: 221+/-26, BB: 225+/-45 mg/l, P=0.024) with a significant linear trend (P < 0.005). Multiple regression showed age and systolic blood pressure, but not Lp(a), to be the main determinants of IMT variability without the contribution of the PON genotype. No consistent differences could be found between genotypes in the peroxidizability of LDL (lag-time, rate of diene production and maximal concentration). Our data support the view that there is no association between the early changes of atherosclerosis as defined by carotid IMT and variation in codon 192 of PON 1.

Age Factors↗

Sexual dysfunction in multiple sclerosis: a MRI, neurophysiological and urodynamic study.

We studied 31 patients with relapsing-remitting (RR) multiple sclerosis (MS) in which we performed an urodynamic study, the pudendal cortical evoked potentials, the tibial cortical evoked potentials and the cranial and cervical spinal cord magnetic resonance imaging (MRI). We calculated the T(1) and T(2) lesion load (LL) and brain parenchymal fraction (BPF) of whole brain, frontal lobes, pons and cervical spinal cord. We also estimated the cross-sectional area at C(2) level. Spearman's rank correlation analysis showed a relationship between symptoms of sexual dysfunction and age (r=0.73, p<0.0001), cognitive performances (r=-0.63, p<0.0001), level of independence (r=-0.63, p<0.0001), disability (r=0.56, p<0.001), symptoms of anxiety (r=0.55, p<0.001) and depression (r=0.50, p<0.005), disease duration (r=0.42, p<0.02) and parenchymal atrophy in the pons (r=-0.38, p=0.031). Sexual dysfunction was not correlated with any other MRI measure, urodynamic patterns or cortical evoked potentials. In multiple regression analysis, sexual dysfunction was predicted only by T(1) lesion load of the pons. In conclusion, we confirmed previous correlations of sexual dysfunction with various clinical variables and demonstrated an association between sexual dysfunction and destructive lesions in the pons, as detected by MRI, in patients with relapsing-remitting multiple sclerosis.

Adult↗

Cavernous angiomas of the brain stem. Intra-axial anatomical pitfalls and surgical strategies.

BACKGROUND: We review the surgical anatomy of the brain stem in relation to the surgical approaches adopted for treatment of cavernomas and identify possible "safe entry zones" on the anterior face of the brainstem. METHODS: Twelve symptomatic patients with cavernoma or telangectasia of the brain stem were surgically treated. The brain stem was divided into the following anatomical areas: ventral medulla, dorsal medulla, dorsal pons, ventral pons, ventral mesencephalon, and dorsal mesencephalon, so that the surgical approach could be "individualized" according to the position of the cavernoma, the nerve fasciculi and nuclei. RESULTS: On the anterior surface of the brain stem a medullar paramedian oblique access to the anterolateral sulcus and a paramedian sagittal pons access seem to avoid the main nerve fasciculi and nuclei. CONCLUSIONS: Although the parenchymal window produced by the cavernoma is the most important parameter for the choice of approach, fairly safe entry zones may be identified even on the anterior surface of the medulla and pons.

Adult↗

Effects of 8-OHDPAT administration into the dorsal raphe nucleus and dorsal hippocampus on fear behavior and regional brain monoamines distribution in rats.

The effects of R(+)-8-hydroxy-dipropylaminotetralin (8-OHDPAT) administration into the dorsal raphe nucleus (DRN) or bilaterally into the dorsal hippocampus (HIP) on fear behavior in a modified version of the light-dark transitions test and regional brain monoamines (NA, DA, 5-HT) and their metabolites (MHPG, DOPAC, 5-HIAA) in the hypothalamus, midbrain central gray matter, amygdala, hippocampus and pons were examined. The experiments were performed on 36 male, 3-month old Wistar rats. Administration of 8-OHDPAT (200 ng) into the DRN reduced time out from the illuminated part of the chamber and time of motionless behavior in the illuminated part, increased the number of returns from the dark to illuminated part and number of head dipping from the dark to illuminated part without effect on time of motionless behavior in the dark part and on time of locomotor activity in the illuminated as well as in dark part of the chamber. HPLC analysis showed reduction of 5-HT content in the midbrain and amygdala, reduction of 5-HIAA content in pons, increased 5-HIAA/5-HT ratio in the hippocampus and increased DOPAC/DA ratio in the hypothalamus, midbrain, hippocampus and pons without affecting the MHPG/NA ratio and NA content. The administration of 8-OHDPAT (100 ng per site) into the HIP reduced time out from the illuminated part of chamber, time of locomotor activity in the illuminated part and head dipping from the dark to illuminated part without effect on the number of returns from the dark to illuminated part, time of locomotor activity in the dark part and time of motionless in the illuminated as well as in the dark part of chamber. HPLC analysis showed reduction of NA content in the hypothalamus, amygdala and pons, increased the MHPG content in all the investigated structures, increased MHPG/NA ratio in all the investigated structures except the hypothalamus. Dopamine content decreased in the hypothalamus and amygdala, and DOPAC/DA ratio increased in the amygdala and hippocampus. Concentrations of 5-HT, 5-HIAA and 5-HIAA/5-HT ratio were unchanged. The results obtained indicate that 8-OHDPAT acting on the pre-synaptic 5-HT1A receptors decreases fear behavior and acting on 5-HT1A post-synaptic receptors increases fear behavior in the light-dark transitions test. The neurochemical base of anxiolytic and anxiogenic effects evoked by 8-OHDPAT is being discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗