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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 937-940, 2021 11.
Article in English | MEDLINE | ID: mdl-34891444

ABSTRACT

Human motion analysis is gaining increased importance in several fields, from movement assessment in rehabilitation to recreational applications such as virtual coaching. Among all the technologies involved in motion capture, Magneto-Inertial Measurements Units (MIMUs) is one of the most promising due to their small dimensions and low costs. Nevertheless, their usage is strongly limited by different error sources, among which magnetic disturbances, which are particularly problematic in indoor environments. Inertial Measurement Units (IMUs) could, thus, be considered as alternative solution. Indeed, relying exclusively on accelerometers and gyroscopes, they are insensitive to magnetic disturbances. Even if the literature has started to propose few algorithms that do not take into account magnetometer input, their application is limited to robotics and aviation. The aim of the present work is to introduce a magnetic-free quaternion based Extended Kalman filter for upper limb kinematic assessment in human motion (i.e., yoga). The algorithm was tested on five expert yoga trainers during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the Mean Absolute Errors (MAEs) and Pearson's correlation coefficients. The achieved worst-case was 6.17°, while the best one was 2.65° for MAEs mean values. The accuracy of the algorithm was further confirmed by the high values of the Pearson's correlation coefficients (lowest mean value of 0.86).Clinical Relevance- The proposed work validated a magnetic free algorithm for kinematic reconstruction with inertial units. It could be used as a wearable solution to track human movements in indoor environments being insensitive to magnetic disturbances, and thus could be potentially used also for rehabilitation purposes.


Subject(s)
Yoga , Biomechanical Phenomena , Humans , Motion , Movement , Upper Extremity
2.
Phys Rev Lett ; 121(4): 041802, 2018 Jul 27.
Article in English | MEDLINE | ID: mdl-30095943

ABSTRACT

A novel mechanism to produce and detect light dark matter in experiments making use of GeV electrons (and positrons) impinging on a thick target (beam dump) is proposed. The positron-rich environment produced by the electromagnetic shower allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}→γ+A^{'}) and resonant (e^{+}+e^{-}→A^{'}) annihilation on atomic electrons. The latter mechanism, for some selected kinematics, results in a larger sensitivity with respect to limits derived by the commonly used A^{'}-strahlung. This idea, applied to beam-dump experiments and active beam-dump experiments, pushes down the current limits by an order of magnitude.

3.
Int J Mol Sci ; 17(10)2016 Oct 22.
Article in English | MEDLINE | ID: mdl-27782075

ABSTRACT

Since involved in synaptic transmission and located on X-chromosome, neuroligins 3 and 4X have been studied as good positional and functional candidate genes for autism spectrum disorder pathogenesis, although contradictory results have been reported. Here, we performed a case-control study to assess the association between noncoding genetic variants in NLGN3 and NLGN4X genes and autism, in an Italian cohort of 202 autistic children analyzed by high-resolution melting. The results were first compared with data from 379 European healthy controls (1000 Genomes Project) and then with those from 1061 Italian controls genotyped by Illumina single nucleotide polymorphism (SNP) array 1M-duo. Statistical evaluations were performed using Plink v1.07, with the Omnibus multiple loci approach. According to both the European and the Italian control groups, a 6-marker haplotype on NLGN4X (rs6638575(G), rs3810688(T), rs3810687(G), rs3810686(C), rs5916269(G), rs1882260(T)) was associated with autism (odd ratio = 3.58, p-value = 2.58 × 10-6 for the European controls; odds ratio = 2.42, p-value = 6.33 × 10-3 for the Italian controls). Furthermore, several haplotype blocks at 5-, 4-, 3-, and 2-, including the first 5, 4, 3, and 2 SNPs, respectively, showed a similar association with autism. We provide evidence that noncoding polymorphisms on NLGN4X may be associated to autism, suggesting the key role of NLGN4X in autism pathophysiology and in its male prevalence.


Subject(s)
Autism Spectrum Disorder/genetics , Cell Adhesion Molecules, Neuronal/genetics , Genetic Predisposition to Disease , Membrane Proteins/genetics , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide , Alleles , Autism Spectrum Disorder/diagnosis , Case-Control Studies , Child , Child, Preschool , Female , Gene Expression , Gene Frequency , Genetic Association Studies , Haplotypes , Humans , Italy , Male , Odds Ratio , Sex Factors
4.
Nutr Neurosci ; 19(1): 43-6, 2016.
Article in English | MEDLINE | ID: mdl-25597866

ABSTRACT

The role of dysbiosis causing leaky gut with xenobiotic production and absorption is increasingly demonstrated in autism spectrum disorder (ASD) pathogenesis. Among xenobiotics, we focused on ochratoxin A (one of the major food contaminating mycotoxin), that in vitro and in vivo exerts a male-specific neurotoxicity probably via microRNA modulation of a specific target gene. Among possible targets, we focused on neuroligin4X. Interestingly, this gene carries some single nucleotide polymorphisms (SNPs) already correlated with the disease and with illegitimate microRNA binding sites and, being located on X-chromosome, could explain the male prevalence. In conclusion, we propose a possible gene-environment interaction triggering ASD explaining the epigenetic neurotoxic mechanism activated by ochratoxin A in genetically predisposed children. This mechanism offers a clue for male prevalence of the disease and may have an important impact on prevention and cure of ASD.


Subject(s)
Autism Spectrum Disorder/epidemiology , Autistic Disorder/epidemiology , Dysbiosis/epidemiology , Epigenesis, Genetic/drug effects , Ochratoxins/toxicity , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/genetics , Autistic Disorder/chemically induced , Autistic Disorder/genetics , Cell Adhesion Molecules, Neuronal/genetics , Cell Adhesion Molecules, Neuronal/metabolism , Child , Chromosomes, Human, X , Gene-Environment Interaction , Humans , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Polymorphism, Single Nucleotide , Prevalence , Sex Factors
5.
J Eur Acad Dermatol Venereol ; 29(2): 383-386, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24404914

ABSTRACT

BACKGROUND: Skin adverse events associated with D-Penicillamine (DPA) are common and multi-faceted, although the presence of DPA or its metabolites has never been documented in the skin, because of inherent difficulties in determining its tissue levels. Thus, the association between DPA and DPA-related dermatoses has been only hypothesized on the basis of careful history, clinical observation and typical histopathological findings. OBJECTIVE: To detect DPA in biopsy specimens in a unique case of 25-year-late-onset elastosis perforans serpiginosa and pseudo-pseudoxanthoma elasticum associated with a history of long-term high dose DPA, by applying a recently described analytical method to assess the presence of DPA in skin. METHODS: We used a reliable analytical method based on high-performance liquid chromatography coupled with amperometric detection to look for the presence of DPA in skin biopsy specimens. RESULTS: A chromatographic peak corresponding to DPA was evidenced in some affected skin samples collected from the patient. CONCLUSION: We documented the effective presence and the persistence after 25 years of DPA in the skin of a woman affected by elastotic cutaneous change due to a long-term therapy with DPA. This report provides further evidence of the relationship between DPA deposit in affected skin and clinical manifestation.


Subject(s)
Chelating Agents/metabolism , Hepatolenticular Degeneration/drug therapy , Penicillamine/metabolism , Skin Diseases/chemically induced , Chelating Agents/therapeutic use , Female , Humans , Middle Aged , Penicillamine/adverse effects , Penicillamine/therapeutic use
6.
J Biomech ; 47(5): 1035-44, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24485513

ABSTRACT

Quantitative motion analysis protocols have been developed to assess the coordination between scapula and humerus. However, the application of these protocols to test whether a subject's scapula resting position or pattern of coordination is "normal", is precluded by the unavailability of reference prediction intervals and bands, respectively. The aim of this study was to present such references for the "ISEO" protocol, by using the non-parametric Bootstrap approach and two parametric Gaussian methods (based on Student's T and Normal distributions). One hundred and eleven asymptomatic subjects were divided into three groups based on their age (18-30, 31-50, and 51-70). For each group, "monolateral" prediction bands and intervals were computed for the scapulo-humeral patterns and the scapula resting orientation, respectively. A fourth group included the 36 subjects (42 ± 13 year-old) for whom the scapulo-humeral coordination was measured bilaterally, and "differential" prediction bands and intervals were computed, which describe right-to-left side differences. Bootstrap and Gaussian methods were compared using cross-validation analyses, by evaluating the coverage probability in comparison to a 90% target. Results showed a mean coverage for Bootstrap from 86% to 90%, compared to 67-70% for parametric bands and 87-88% for parametric intervals. Bootstrap prediction bands showed a distinctive change in amplitude and mean pattern related to age, with an increase toward scapula retraction, lateral rotation and posterior tilt. In conclusion, Bootstrap ensures an optimal coverage and should be preferred over parametric methods. Moreover, the stratification of "monolateral" prediction bands and intervals by age appears relevant for the correct classification of patients.


Subject(s)
Humerus/physiology , Scapula/physiology , Shoulder Joint/physiology , Adolescent , Adult , Aged , Arm/physiology , Female , Humans , Male , Middle Aged , Normal Distribution , Reference Values , Rotation , Shoulder/physiology , Young Adult
7.
Article in English | MEDLINE | ID: mdl-24161666

ABSTRACT

The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences seem to affect the entire interaction between hyper-arousal, reduced hormonal response to stress and addiction severity. Our findings, although obtained in a small number of subjects, indicate a significant link between the perception of parental style/care/support during childhood and the ability to cope with stressful emotional stimuli in adulthood and addiction severity.


Subject(s)
Arousal/physiology , Child Abuse/psychology , Heroin Dependence/complications , Heroin Dependence/psychology , Mood Disorders/etiology , Adolescent , Adrenocorticotropic Hormone/blood , Adult , Analysis of Variance , Child , Child, Preschool , Heroin Dependence/blood , Humans , Hydrocortisone/blood , Infant , Linear Models , Male , Mood Disorders/blood , Psychiatric Status Rating Scales , Severity of Illness Index , Surveys and Questionnaires , Young Adult
8.
World J Biol Psychiatry ; 15(4): 327-33, 2014 May.
Article in English | MEDLINE | ID: mdl-24286295

ABSTRACT

OBJECTIVES: The one-carbon metabolism, also known as methionine-homocysteine cycle, governs the dynamics of DNA methylation, epigenetically regulating gene expression, and has been reported altered in anorexia nervosa (AN) adult patients. The aim of this study consisted in assessing whole-blood DNA methylation in adolescent AN patients, assessing its significance in relationship to clinical and hormonal variables. METHODS: Whole-blood global DNA methylation was measured as incorporation of [(3)H]dCTP following HpaII cut in 32 adolescent females affected by restrictive type AN and compared to 13 healthy controls. Homocysteine, vitamin B12 and folate plasma levels were assessed as well as fasting plasma levels of leptin and steroid hormones. Clinical variables, including severity and associate states and traits, were assessed by means of the EDI-3, CDI and STAI-Y scales. RESULTS: We confirm that whole-blood global DNA methylation is modestly albeit significantly reduced in AN adolescents with respect to controls, correlating with plasma leptin and steroid hormone levels. Conversely, clinical traits did not correlate with the outcome variable. CONCLUSIONS: A better definition of the epigenetic dysregulation underlying AN pathology or vulnerability might lead to develop useful markers for diagnosis, prognostic classification and tailored therapeutic interventions in these vulnerable patients since the earliest phases of their disease.


Subject(s)
Anorexia Nervosa/blood , DNA Methylation/physiology , Gonadal Steroid Hormones/blood , Hydrocortisone/blood , Leptin/blood , Adolescent , Biomarkers/blood , Female , Humans
9.
Curr Med Chem ; 19(12): 1846-63, 2012.
Article in English | MEDLINE | ID: mdl-22414078

ABSTRACT

New-generation antidepressants are a heterogeneous class of drugs used in the treatment of depression and related disorders. This review deals with the first new-generation antidepressant class to enter the pharmaceutical market, i.e., selective serotonin reuptake inhibitors (SSRIs), which are still the most prescribed and widely used ones. Their common characteristics are the comparable clinical efficacy, good tolerability and relative safety in comparison to "first generation antidepressants", i.e. classic tricyclic antidepressants and monoamine oxidase inhibitors. This class of drugs includes fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review, the main pharmacodynamic and pharmacokinetic properties of the six commercially available SSRIs are described, focusing on side and toxic effects, chemical-clinical correlations, interactions with other drugs, the role of therapeutic drug monitoring (TDM) and related bioanalytical methodologies.


Subject(s)
Depressive Disorder/drug therapy , Drug Monitoring , Selective Serotonin Reuptake Inhibitors/therapeutic use , Benzofurans/adverse effects , Benzofurans/pharmacokinetics , Benzofurans/therapeutic use , Citalopram/adverse effects , Citalopram/pharmacokinetics , Citalopram/therapeutic use , Depressive Disorder/metabolism , Fluoxetine/adverse effects , Fluoxetine/pharmacokinetics , Fluoxetine/therapeutic use , Fluvoxamine/adverse effects , Fluvoxamine/pharmacokinetics , Fluvoxamine/therapeutic use , Humans , Indoles/adverse effects , Indoles/pharmacokinetics , Indoles/therapeutic use , Paroxetine/adverse effects , Paroxetine/pharmacokinetics , Paroxetine/therapeutic use , Piperazines/adverse effects , Piperazines/pharmacokinetics , Piperazines/therapeutic use , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Sertraline/adverse effects , Sertraline/pharmacokinetics , Sertraline/therapeutic use , Vilazodone Hydrochloride
10.
Eur J Histochem ; 55(1): e6, 2011 Feb 25.
Article in English | MEDLINE | ID: mdl-21556121

ABSTRACT

Histidine-rich glycoprotein (HRG) is synthesized by liver and is present at relatively high concentration in the plasma of vertebrates. We have previously described the association of a HRG-like molecule to purified rabbit skeletal muscle AMP deaminase (AMPD). We also provided the first evidence for the presence of a HRG-like protein in human skeletal muscle where a positive correlation between HRG content and total determined AMPD activity has been shown. In the present paper we investigate the origin of skeletal muscle HRG. The screening of a human skeletal muscle cDNA expression library using an anti-HRG antibody failed to reveal any positive clone. The RT-PCR analysis, performed on human skeletal muscle RNA as well as on RNA from the rhabdomyosarcoma (RD) cell line, failed to show any mRNA specific for the plasma HRG or for the putative muscle variant. When the RD cells were incubated with human plasma HRG, a time-dependent increase of the HRG immunoreactivity was detected both at the plasma membrane level and intracellularly. The internalisation of HRG was inhibited by the addition of heparin. The above data strongly suggest that skeletal muscle cells do not synthesize the muscle variant of HRG but instead can actively internalise it from plasma.


Subject(s)
AMP Deaminase/metabolism , Blood Proteins/metabolism , Muscle, Skeletal/metabolism , Proteins/metabolism , Blood Proteins/genetics , Cell Line, Tumor , Electrophoresis, Polyacrylamide Gel , Endocytosis/physiology , Genetic Variation , Humans , Muscle, Skeletal/enzymology , Protein Binding , Proteins/genetics , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Rhabdomyosarcoma/pathology
11.
J Pharm Biomed Anal ; 54(3): 562-7, 2011 Feb 20.
Article in English | MEDLINE | ID: mdl-21035976

ABSTRACT

The aim of the study was the development of analytical methods suitable for the quantification of L-dopa, carbidopa and entacapone in plasma of Parkinsonian patients treated with Stalevo(®). The metabolite 3-O-methyldopa was also determined to obtain some indications on the pharmacokinetics of L-dopa. For the simultaneous analysis of L-dopa, 3-O-methyldopa and carbidopa, a RP C18 column as the stationary phase and a mixture of methanol and a pH 2.88 phosphate buffer (8:92, v/v) as the mobile phase were used. A feasible plasma pre-treatment based on protein precipitation was implemented, obtaining extraction yield higher than 94% for all the analytes. For the analysis of entacapone a RP C8 column and a mixture of methanol, acetonitrile and a pH 1.90 phosphate buffer as the mobile phase (17.5:22.5:60, v/v/v) were used. A plasma pre-treatment procedure was developed, based on solid phase extraction of entacapone using Oasis HLB cartridges. Extraction yields were good, being always higher than 96%. Both methods, based on HPLC-ED (V=+0.8V), have been fully validated. Good linearity was obtained over the following concentration ranges: 100-4000 ng mL(-1) for L-dopa, 200-10,000 ng mL(-1) for 3-O-methyldopa, 25-4000 ng mL(-1) for carbidopa and 20-4000 ng mL(-1) for entacapone. Precision data were satisfactory, being R.S.D.% values lower than 5.64%; accuracy also resulted very good with recovery data higher than 90%. The proposed methods have been successfully applied to the analysis of patient plasma samples and seem to be suitable for therapeutic drug monitoring purposes.


Subject(s)
Antiparkinson Agents/blood , Antiparkinson Agents/therapeutic use , Carbidopa/blood , Catechols/blood , Catechols/therapeutic use , Levodopa/blood , Methyldopa/blood , Nitriles/blood , Calibration , Carbidopa/pharmacokinetics , Carbidopa/therapeutic use , Catechols/pharmacokinetics , Chromatography, High Pressure Liquid , Drug Combinations , Humans , Levodopa/pharmacokinetics , Levodopa/therapeutic use , Methyldopa/pharmacokinetics , Nitriles/pharmacokinetics , Reproducibility of Results , Solid Phase Extraction
12.
Neurosci Biobehav Rev ; 35(8): 1771-8, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21145351

ABSTRACT

Epidemiological and clinical data show frequent associations between adverse childhood experiences (ACEs) and substance abuse susceptibility particularly in adolescents. A large body of evidences suggests that the possible dysregulation of neuroendocrine responses as well as neurotransmitters function induced by childhood traumatic experiences and emotional neglect could constitute one of the essential biological changes implementing substance abuse vulnerability. Moreover, genotype variables and its environment interactions have been associated with an increased risk for early onset substance abuse. In this paper we present several data that support the hypothesis of the involvement of hypothalamus-pituitary-adrenal (HPA) axis in mediating the combined effect of early adverse experiences and gene variants affecting neurotransmission. The presented data also confirm the relationship between basal plasma levels of cortisol and ACTH, on the one hand, and retrospective measures of neglect during childhood on the other hand: the higher the mother and father neglect (CECA-Q) scores are, the higher the plasma levels of the two HPA hormones are. Furthermore, such positive relationship has been proved to be particularly effective and important when associated with the "S" promoter polymorphism of the gene encoding the 5-HTT transporter, both in homozygote and heterozygote individuals.


Subject(s)
Child Abuse , Hypothalamo-Hypophyseal System/physiology , Pituitary-Adrenal System/physiology , Plasma Membrane Neurotransmitter Transport Proteins/genetics , Substance-Related Disorders/psychology , Adaptation, Psychological , Adolescent , Age Factors , Child , Child, Preschool , Critical Period, Psychological , Humans , Neurosecretory Systems/physiology , Plasma Membrane Neurotransmitter Transport Proteins/physiology , Polymorphism, Genetic , Resilience, Psychological , Substance-Related Disorders/genetics , Substance-Related Disorders/physiopathology
13.
Transplant Proc ; 42(10): 4049-52, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21168624

ABSTRACT

INTRODUCTION: Since previous in vitro studies suspected the metabolite mycophenolate acyl-glucuronide (AcMPAG) to be responsible for the gastrointestinal side effects, we examined the correlation between AcMPAG blood levels and patient gastrointestinal satisfaction inquiries using a standardized, validated questionnaire. PATIENTS AND METHODS: We enrolled 63 renal transplant patients, however, two discontinued the study and 16 were excluded because of inadequate completion of the questionnaires or missing blood values or discontinuation of enteric coated mycophenolic acid (EC-MPA) therapy, severe side effects or viral infections. The final responses of 45 people were subjects to statistical analysis. Gastrointestinal side effects were examined using the Gastrointestinal Symptom Rating Scale (GSRS) completed at three times: T1 (3-5 days after transplantation), T2 (10-15 days), and T3 (3 months). The GSRS results generated two groups of patients based on cutoff values set at a score of 4 points for each item. Scores less than 4 were assumed to be "no side effects"; ≥4, "side effects." AcMPAG was measured by mass spectroscopy on blood samples obtained at fixed times generating three pharmacokinetic profiles per patient. RESULTS: There was no relation between high AcMPAG blood concentrations and gastrointestinal dissatisfaction. Neither Ac-MPAG area under the curve (AUC) in the absorption phase nor AcMPAG peak values correlated with gastrointestinal dissatisfaction. CONCLUSION: There was no significant correlation between mean AcMPAG and GSRS scores, although previous studies had suggested AcMPAG maximum values or alternatively AcMPAG AUC in the absorption phase to relate to side effects.


Subject(s)
Gastrointestinal Tract/drug effects , Glucuronides/blood , Immunosuppressive Agents/blood , Kidney Transplantation , Mycophenolic Acid/analogs & derivatives , Area Under Curve , Glucuronides/pharmacokinetics , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/pharmacokinetics , Mycophenolic Acid/blood , Mycophenolic Acid/pharmacokinetics , Patient Satisfaction , Prospective Studies , Surveys and Questionnaires
14.
J Pharm Biomed Anal ; 53(3): 682-7, 2010 Nov 02.
Article in English | MEDLINE | ID: mdl-20580512

ABSTRACT

A reliable chromatographic method for the determination of soy isoflavones (genistein, daidzein and glycitein) using a coulometric detection has been developed and applied to analyse plasma of postmenopausal women. The chromatographic separation was performed on a C18 reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. Coulometric detection was carried out at +0.500 V. A careful and rapid solid phase extraction procedure on hydrophilic/lipophilic cartridges was chosen for plasma sample purification with and without hydrolysis obtaining good extraction yield values for all the analytes (>90.0%). The enzymatic hydrolysis step was necessary for the determination of the total amount of soy isoflavones. The limit of quantitation was 0.5 ng mL(-1) for genistein and 0.25 ng mL(-1) for daidzein and glycitein. The method was found to be precise and accurate. Thus, the proposed method is suitable for the analysis of soy isoflavones (free and total amounts) in plasma of postmenopausal women under treatment with the SoymenGN dietary supplement.


Subject(s)
Chromatography, High Pressure Liquid/methods , Genistein/blood , Isoflavones/blood , Postmenopause/blood , Electrochemistry , Female , Humans , Middle Aged , Solid Phase Extraction
15.
Brain Res ; 1325: 112-20, 2010 Apr 14.
Article in English | MEDLINE | ID: mdl-20153734

ABSTRACT

We used Flinder Sensitive Line (FSL) rats, a genetic model of unipolar depression, to examine whether changes in central GABAergic transmission are associated with a depressed phenotype. FSL rats showed an increased behavioral response to low doses of diazepam, as compared to either Sprague Dawley (SD) or Flinder Resistant Line (FRL) rats used as controls. Diazepam at a dose of 0.3 mg/kg, i.p., induced a robust impairment of motor coordination in FSL rats, but was virtually inactive in SD or FRL rats. The increased responsiveness of FSL rats was not due to changes in the brain levels of diazepam or its active metabolites, or to increases in the number or affinity of benzodiazepine recognition sites, as shown by the analysis of [(3)H]-flunitrazepam binding in the hippocampus, cerebral cortex or cerebellum. We therefore examined whether FSL rats differed from control rats for the expression levels of the K(+)/Cl(-) cotransporter, KCC2, which transports Cl(-) ions out of neurons, thus creating the concentration gradient that allows Cl(-) influx through the anion channel associated with GABA(A) receptors. Combined immunoblot and immunohistochemical data showed a widespread increase in KCC2 expression in FSL rats, as compared with control rats. The increase was more prominent in the cerebellum, where KCC2 was largely expressed in the granular layer. These data raise the interesting possibility that a spontaneous depressive state in animals is associated with an amplified GABAergic transmission in the CNS resulting from an enhanced expression of KCC2.


Subject(s)
Cerebellum/metabolism , Cerebral Cortex/metabolism , Depressive Disorder/metabolism , Hippocampus/metabolism , Symporters/metabolism , Animals , Central Nervous System Agents/administration & dosage , Central Nervous System Agents/pharmacokinetics , Central Nervous System Agents/pharmacology , Cerebellum/drug effects , Cerebral Cortex/drug effects , Diazepam/administration & dosage , Diazepam/pharmacokinetics , Diazepam/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Hippocampus/drug effects , Male , Motor Skills/drug effects , Rats , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Species Specificity , K Cl- Cotransporters
16.
J Pharm Biomed Anal ; 50(3): 501-6, 2009 Oct 15.
Article in English | MEDLINE | ID: mdl-19524386

ABSTRACT

Orphenadrine is an antimuscarinic agent mainly used for the treatment of parkinsonism and to alleviate the neuroleptic syndrome induced by antipsychotic drugs. A new, rapid analytical method, based on liquid chromatography with diode array detection (DAD), has been developed and applied to the determination of orphenadrine in plasma of schizophrenic patients for therapeutic drug monitoring and toxicological purposes. The chromatographic separation was performed on a pentafluorophenyl reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. DAD detection was carried out at 220 nm. A careful and rapid solid-phase extraction procedure on cyanopropyl cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for the analyte (>96.0%). The assays showed a linear response for orphenadrine (30-1000 ng mL(-1)). The method is also precise and selective. Thus, the method developed seems to be suitable for routine analysis of orphenadrine in psychiatric patients. Moreover, it was applied to plasma samples from a psychotic patient who had tried to poison himself with 1000 mg of orphenadrine and was undergoing polypharmacy.


Subject(s)
Chromatography, High Pressure Liquid/methods , Drug Monitoring/methods , Muscarinic Antagonists/blood , Orphenadrine/blood , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Dose-Response Relationship, Drug , Drug Overdose , Humans , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/poisoning , Neuroleptic Malignant Syndrome/drug therapy , Neuroleptic Malignant Syndrome/etiology , Orphenadrine/administration & dosage , Orphenadrine/poisoning , Schizophrenia/drug therapy
17.
Neurosci Biobehav Rev ; 33(4): 601-10, 2009 Apr.
Article in English | MEDLINE | ID: mdl-17904221

ABSTRACT

UNLABELLED: Childhood neglect and poor child-parent relationships have been reported to increase substance use disorders susceptibility. Stressful environmental factors, including emotional neglect, could affect individual personality traits and mental health, possibly inducing stable changes in hypothalamic-pituitary-adrenal (HPA) axis and brain mono-amine function, in turn involved in addictive behavior vulnerability. Therefore, we decided to investigate homovanillic (HVA) and prolactin (PRL) plasma levels, as expression of possible changes in dopamine function, ACTH and cortisol plasma levels, as measures of HPA axis function, and concomitant psychiatric symptoms profile in abstinent cocaine addicts, in relationship to their childhood history of neglect and poor parental care perception. METHODS: Fifty abstinent cocaine dependent patients, and 44 normal controls, matched for age and sex, were submitted to a detailed psychiatric assessment (DSM IV criteria). All patients and controls completed the Symptoms Check List-90 (SCL-90) and the Buss Durkee Hostility Inventory (BDHI), to evaluate psychiatric symptoms frequency and aggressiveness levels. The Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and Parental Bonding Instrument (PBI) have been used to retrospectively investigate parent-child relationships. Blood samples were collected to determine HVA, PRL, ACTH and cortisol basal plasma levels. RESULTS: Cocaine addicted individuals in general showed significantly lower HVA, and higher PRL, ACTH and cortisol basal levels respect to controls. In particular, neuroendocrine changes characterized cocaine addicts with childhood history of neglect and low perception of parental care. Obsessive-compulsive, depression and aggressiveness symptoms have been found related to poor parenting, inversely associated to HVA levels and directly associated to PRL, ACTH and cortisol levels. CONCLUSIONS: These findings suggest the possibility that childhood experience of neglect and poor parent-child attachment may partially contribute to a complex neurobiological derangement including HPA axis and dopamine system dysfunctions, playing a crucial role in addictive and affective disorders susceptibility.


Subject(s)
Child Abuse , Cocaine-Related Disorders/psychology , Mental Disorders , Parenting/psychology , Adolescent , Adrenocorticotropic Hormone/blood , Adult , Child , Child, Preschool , Chromatography, High Pressure Liquid/methods , Electrochemistry , Female , Homovanillic Acid/blood , Humans , Hydrocortisone/blood , Male , Mental Disorders/blood , Mental Disorders/physiopathology , Mental Disorders/psychology , Personality , Prolactin/blood , Regression Analysis , Retrospective Studies , Surveys and Questionnaires , Young Adult
18.
Pediatr Med Chir ; 30(6): 281-9, 2008.
Article in Italian | MEDLINE | ID: mdl-19431950

ABSTRACT

The frequency of early-onset neonatal sepsis without prophylaxis is 1-5/1.000 live births. Since year '70 the most frequent causative microorganism is the group B Streptococcus (S. agalactiae, GBS), followed by Escherichia coli. The mortality rate is now reduced to 4% due to the improvement of neonatal intensive care. In the USA, the incidence of GBS early-onset neonatal sepsis has been markedly reduced by the application of the guidelines released by the Centers for Disease Control (CDC). This strategy, however, is not effective on occurrence of late-onset neonatal group B streptococcal disease. In Italy, the application of CDC guidelines is not customary, and different, often complex, protocols of obstetrical-neonatological integrated approach are applied. The frequency of infectious risk has made the GBS a paramount problem for the neonatologist, even for the legal responsibility issues resulting from the multiplicity of possible options. To reach the best level of protection of the newborn against early-onset GBS infection, the working group of providers of prenatal, obstetric, and neonatal care of the functional area of Cuneo issued an integrated protocol, in order to perform the GBS screening with the optimal culture method suggested by CDC guidelines in the highest possible number of pregnant women, and to standardize the obstetrical and neonatal management.


Subject(s)
Pregnancy Complications, Infectious/diagnosis , Streptococcal Infections/prevention & control , Streptococcus agalactiae , Adult , Age Factors , Algorithms , Anti-Bacterial Agents/pharmacology , Clindamycin/pharmacology , Clinical Protocols , Erythromycin/pharmacology , Female , Humans , Infant, Newborn , Intensive Care, Neonatal , Italy , Microbial Sensitivity Tests , Practice Guidelines as Topic , Pregnancy , Prevalence , Rectum/microbiology , Risk Factors , Streptococcal Infections/diagnosis , Streptococcal Infections/epidemiology , Streptococcal Infections/mortality , Streptococcal Infections/transmission , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/isolation & purification , United States , Vagina/microbiology
19.
J Neural Transm (Vienna) ; 114(12): 1637-47, 2007.
Article in English | MEDLINE | ID: mdl-17690947

ABSTRACT

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) seems to be a risk condition for substance use disorders, possibly in relationship to common neurobiological changes, underlying both addictive and externalising behaviour susceptibility. Although this vulnerability has been primarily attributed to gene variants, previous studies suggest that also adverse childhood experiences may influence neurotransmission, affecting in particular brain dopamine (DA) system and possibly concurring to the development of behavioural disorders. Therefore, we decided to investigate ADHD symptoms and plasma concentrations of the DA metabolite homovanillic acid (HVA) in abstinent addicted patients, in comparison with healthy control subjects, evaluating whether ADHD scores were related with HVA levels, as expression of DA turnover, and whether HVA values, in turn, were associated with childhood emotional neglect. METHODS: Eighty-two abstinent drug dependent patients, and 44 normal controls, matched for age and sex, completed the Wender Utah Rating Scale (WURS), measuring ADHD symptoms, and the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Blood samples were collected to determine HVA plasma levels. RESULTS: Addicted individuals showed significantly higher ADHD scores and lower HVA levels respect to control subjects. ADHD scores at WURS in addicted patients negatively correlated with plasma HVA values. In turn, plasma HVA levels were inversely associated with childhood neglect measures, reaching statistical significance with "mother-antipathy" and "mother neglect" scores. CONCLUSIONS: These findings suggest the possibility that childhood experience of neglect and poor mother-child attachment may have an effect on central dopamine function as an adult, in turn contributing to both ADHD and substance abuse neurobiological vulnerability.


Subject(s)
Attention Deficit Disorder with Hyperactivity/blood , Attention Deficit Disorder with Hyperactivity/epidemiology , Child Abuse , Homovanillic Acid/blood , Substance-Related Disorders/blood , Substance-Related Disorders/epidemiology , Adult , Antisocial Personality Disorder/epidemiology , Anxiety/complications , Attention Deficit Disorder with Hyperactivity/psychology , Child , Child Abuse/psychology , Comorbidity , Depressive Disorder, Major/epidemiology , Female , Humans , Male , Substance-Related Disorders/psychology
20.
Transplant Proc ; 39(2): 505-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362768

ABSTRACT

There is only limited information about recipient risk factors for graft survival in living- donor kidney transplantation. This study aimed to investigate prognostic factors and their impact on living-related and unrelated renal transplant recipients. From October 2000 until October 2004, 81 adult living-related renal transplantations were performed at our institution. Using multivariate analysis, the association of the following variables with kidney graft outcome was studied: ages of donors and recipients, gender and body mass index, cold and warm ischemia, HLA mismatches, identity and compatibility of blood group, duration of dialysis, cytomegalovirus (CMV) status, recipient original disease, surgical and general complications, and status of retransplantation. Multivariate analysis revealed significant reduction of graft function and graft survival in recipients with retransplantation, more than 4 mismatches, and a high body mass index. Thus, living-donor kidney transplantation can be regarded as a safe and standardized operation relating to surgical technique, but further consideration of the recipient body mass index and the number of mismatches are recommended during the preparation for transplantation.


Subject(s)
Kidney Transplantation/adverse effects , Kidney Transplantation/physiology , Living Donors , Adult , Blood Group Incompatibility/epidemiology , Female , Histocompatibility Testing , Humans , Kidney Transplantation/immunology , Male , Middle Aged , Postoperative Complications/epidemiology , Reoperation/statistics & numerical data , Risk Assessment , Treatment Failure , Treatment Outcome
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