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1.
Arch Clin Neuropsychol ; 39(1): 24-34, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-37530515

ABSTRACT

OBJECTIVES: To describe the characteristics of patients receiving a clinical referral for neuropsychological evaluation in two Huntington's Disease Society of America Centers of Excellence (HDSA COE). In this exploratory pilot study, we used an empirically supported clinical neuropsychological battery to assess differences in cognitive performance between premanifest and manifest HD patient groups (compared with each other and normative expectations). METHOD: Clinical data from 76 adult genetically confirmed patients referred for neuropsychological evaluations was retrospectively collected from two HDSA COEs. ANOVA and Chi-square tests were used to compare variables between pre-manifest (n = 14) and manifest (n = 62) groups for demographic, cognitive, neuropsychiatric, and disease severity variables. RESULTS: Our clinics serviced a disproportionate number of motor manifest patients. Six measures were excluded from analyses due to infrequent administration. The full WAIS-IV Digit Span was disproportionately administered to the manifest group. The premanifest group showed stronger cognitive performance with effect sizes in the large range on subtests of the WAIS-IV Digit Span, HVLT-R, SDMT, and verbal fluency. CONCLUSIONS: This is the first study to assess an empirically supported neuropsychological research battery in a clinical setting with a relatively large sample size given the rarity of HD. The battery adequately captured areas of impairment across the disease spectrum. Application of the current battery with larger premanifest samples is warranted.


Subject(s)
Huntington Disease , Adult , Humans , Huntington Disease/complications , Huntington Disease/psychology , Pilot Projects , Retrospective Studies , Neuropsychological Tests
2.
Reprod Sci ; 31(4): 987-996, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38030813

ABSTRACT

The use of plasma cell-free DNA (cfDNA) as a useful biomarker in obstetric clinical practice has been delayed due to the lack of reliable quantification protocols. We developed a protocol to quantify plasma cfDNA using an internal standard strategy to overcome difficulties posed by low levels and high fragmentation of cfDNA. cfDNA was isolated from plasma samples of non-pregnant (NP, n = 26) and pregnant (P, n = 26) women using a commercial kit and several elution volumes were evaluated. qPCR parameters were optimized for cfDNA quantification, and several quantities of a recombinant standard were evaluated as internal standard. Absolute quantification was performed using a standard curve and the quality of the complete method was evaluated. cfDNA was eluted in a 50-µl volume, actin-ß (ACTB) was selected as the target gene, and qPCR parameters were optimized. The ACTB standard was constructed and 1000 copies were selected as internal standard. The standard curve showed R2 = 0.993 and E = 109.7%, and the linear dynamic range was defined between 102 and 106 ACTB copies/tube. Repeatability and reproducibility in terms of CV were 19% and up to 49.5% for ACTB copies per milliliter of plasma, respectively. The range of cfDNA levels was 428-18,851 copies/mL in NP women and 4031-2,019,363 copies/mL in P women, showing significant differences between the groups. We recommend the application of internal standard strategy for a reliable plasma cfDNA quantification. This methodology holds great potential for a future application in the obstetric field.


Subject(s)
Cell-Free Nucleic Acids , Pregnant Women , Humans , Female , Pregnancy , Reproducibility of Results , Cell-Free Nucleic Acids/genetics , Biomarkers
3.
Psychogeriatrics ; 24(2): 223-232, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38098187

ABSTRACT

BACKGROUND: Caregivers of persons with cognitive decline (PWCD) are at increased risk of poor sleep quantity and quality. It is unclear whether this is due to factors in the caregiver versus in the PWCD. METHODS: This secondary data analysis using Aging, Demographics, and Memory Study data from the Health Retirement Study examined factors contributing to reduced sleep/rest among spouses and caregivers of older adults with varying levels of cognitive decline (cognitively normal (CN), cognitive impairment but not dementia (CIND), or dementia). RESULTS: In our preliminary analysis, among N = 218 spouses (not necessarily caregivers) (mean age (SD) = 73.77 (7.30); 70.64% female) of older adults with varying levels of cognitive decline, regression revealed that frequency of sleep complaints was lowest among spouses with CN partners, second highest with CIND partners, and highest with dementia-partners, X2 = 26.810, P = 0.002. PRIMARY AIM: among n = 136 caregivers of PWCD (mean age (SD) = 59.27 (13.97); 74.26% female; 22.79% spouses), we analyzed whether caregiver reduced sleep/rest was predicted by PWCD factors (i.e., frequent nighttime waking, dementia severity) and/or caregiver factors (i.e., depression symptoms, caregiver role overload). Regression revealed that caregiver depression symptoms (d = 0.62) and role overload (d = 0.88), but not PWCD factors, were associated with reduced caregiver sleep/rest after adjusting for demographic factors, caregiving frequency, and shared-dwelling status (overall model: X2 = 31.876, P = 0.002). Exploratory analyses revealed that a caregiver was 7.901 times more likely (95% CI: 0.99-63.15) to endorse experiencing reduced sleep/rest if back-up care was not available (P = 0.023). CONCLUSION: Findings highlight that the frequency of reported sleep problems among spouses increases in a stepwise fashion when partners have dementia versus CIND versus CN. The results also emphasise that caregiver mental health and burden are strongly associated with caregiver sleep disturbances and thus may be targets of intervention for caregiver sleep problems.


Subject(s)
Cognitive Dysfunction , Dementia , Sleep Wake Disorders , Female , Humans , Aged , Male , Caregivers , Spouses , Sleep , Cognitive Dysfunction/epidemiology , Sleep Wake Disorders/epidemiology , Dementia/epidemiology
4.
Mov Disord Clin Pract ; 10(12): 1714-1724, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38094638

ABSTRACT

Background: The clinical diagnosis of manifest Huntington's disease (HD) relies on a high level of clinical confidence (99% confidence) of HD-consistent motor signs. Longitudinal data have reliably identified cognitive and behavioral dysfunction predating clinical motor diagnosis by up to 15 years. Reliance on motor signs to establish a diagnosis of HD increases risk of early misdiagnosis or delayed diagnosis. Clinical neuropsychologists are uniquely positioned to advise on the clinical application of the Movement Disorder Society Task Force's recently proposed non-motor diagnostic criteria for HD. Objectives: To provide (1) a recommended clinical approach toward non-motor diagnostic criteria in persons with HD and facilitation of accurate diagnosis; (2) recommended practices for medical treatment providers to screen and longitudinally monitor non-motor signs of HD. Methods: The Huntington Study Group re-established the Neuropsychology Working Group, then recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to conduct an unstructured literature review and discuss expert opinions on practice, to facilitate an informal consensus opinion to accomplish the objectives. Results: The opinion and an example protocol for medical treatment providers to screen, monitor, and triage non-motor signs and symptoms of Huntington's disease is provided. Conclusions: Clinical diagnosis of non-motor HD is empirically justified and clinically important. Screening and triage by non-neuropsychologist clinicians can aid in detecting and monitoring non-motor Huntington's disease manifestation. The Neuropsychology Working Group consensus advances good clinical practice, clinical research, and quality of life. A companion position paper presenting the details of our consensus opinion regarding evidence-based guidelines for neuropsychological practice is forthcoming.

5.
Clin Neuropsychol ; : 1-23, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37849335

ABSTRACT

Objective: Neuropsychological evaluation is critical to detection and management of cognitive and neuropsychiatric changes associated with Huntington disease (HD). Accurate assessment of non-motor complications of HD is critical given the prominent impact on functional disability, frequently commensurate with or exceeding that of motor symptoms. The increasing emphasis on developing disease-modifying therapies targeting cognitive decline in HD requires consensus on clinical neuropsychological assessment methods. The Neuropsychology Working Group (NPWG) of the Huntington Study Group (HSG) sought to provide evidence and consensus-based, practical guidelines for the evaluation of cognitive and neuropsychiatric symptoms associated with HD. Method: The NPWG recruited a multi-disciplinary group of neuropsychologists, neurologists, and psychiatrists to inform best practices in assessing, diagnosing, and treating the non-motor symptoms in HD. A review was circulated among the NPWG, and in an iterative process informed by reviewed literature, best practices in neuropsychological evaluation of patients with HD were identified. Results: A brief review of the available literature and rational for a clinical consensus battery is offered. Conclusion: Clinical neuropsychologists are uniquely positioned to both detect and characterize the non-motor symptoms in HD, and further, provide neurologists and allied health professions with clinically meaningful information that impacts functional outcomes and quality of life. The NPWG provides guidance on best practices to clinical neuropsychologists in this statement. A companion paper operationalizing clinical application of previous research-based non-motor diagnostic criteria for HD is forthcoming, which also advises on non-motor symptom screening methods for the non-neuropsychologist working with HD.

7.
Epidemiol Psychiatr Sci ; 31: e90, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36510831

ABSTRACT

The approach-avoidance conflict (AAC), i.e. the competing tendencies to undertake goal-directed actions or to withdraw from everyday life challenges, stands at the basis of humans' existence defining behavioural and personality domains. Gray's Reinforcement Sensitivity Theory posits that a stable bias toward approach or avoidance represents a psychopathological trait associated with excessive sensitivity to reward or punishment. Optogenetic studies in rodents and imaging studies in humans associated with cross-species AAC paradigms granted new emphasis to the hippocampus as a hub of behavioural inhibition. For instance, recent functional neuroimaging studies show that functional brain activity in the human hippocampus correlates with threat perception and seems to underlie passive avoidance. Therefore, our commentary aims to (i) discuss the inhibitory role of the hippocampus in approach-related behaviours and (ii) promote the integration of functional neuroimaging with cross-species AAC paradigms as a means of diagnostic, therapeutic, follow up and prognosis refinement in psychiatric populations.


Subject(s)
Punishment , Reward , Humans , Hippocampus , Motivation , Personality
8.
Transpl Immunol ; 69: 101447, 2021 12.
Article in English | MEDLINE | ID: mdl-34400246

ABSTRACT

BACKGROUND/OBJECTIVES: Rejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants. METHODS: This was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel. RESULTS: Our study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance. CONCLUSIONS: To our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.


Subject(s)
Cytokines , Graft Rejection , Chemokines , Cross-Sectional Studies , Graft Rejection/diagnosis , Humans , Prospective Studies
9.
Case Rep Genet ; 2020: 8873219, 2020.
Article in English | MEDLINE | ID: mdl-33123388

ABSTRACT

Porphyrias are a heterogeneous group of metabolic disorders that result from the altered activity of specific enzymes of the heme biosynthetic pathway and are characterized by accumulation of pathway intermediates. Porphyria cutanea tarda (PCT) is the most common porphyria and is due to deficient activity of uroporphyrinogen decarboxylase (UROD). Acute intermittent porphyria (AIP) is the most common of the acute hepatic porphyrias, caused by decreased activity of hydroxymethylbilane synthase (HMBS). An Argentinean man with a family history of PCT who carried the UROD variant c.10_11insA suffered severe abdominal pain. Biochemical testing was consistent with AIP, and molecular analysis of HMBS revealed a de novo variant: c.344 + 2_ + 5delTAAG. This is one of the few cases of porphyria identified with both UROD and HMBS mutations and the first confirmed case of porphyria with dual enzyme deficiencies in Argentina.

10.
Mol Cell Endocrinol ; 510: 110820, 2020 06 15.
Article in English | MEDLINE | ID: mdl-32315720

ABSTRACT

Agrochemicals or pesticides are compounds widely used to prevent, destroy or mitigate pests such as insects, rodents, herbs and weeds. However, most of them also act as environmental estrogens, anti-estrogens and/or antiandrogenic chemicals. In addition, both herbicides (such as glyphosate and paraquat) and insecticides (such as pyrethroids, organophosphates, neonicotinoids and rotenone) have been shown to exert significant adverse effects on hippocampal neurogenesis. These effects are particularly important because neurogenesis dysregulation could be associated with cognitive decline and neuropathologies such as Alzheimer's disease. This review focuses on the most commonly used agrochemicals in Argentina and their effects on the hippocampal neurogenesis of mammals. It also discusses the disruption of hormone synthesis and action as a possible mechanism through which these chemical compounds could alter the brain functions. Finally, we propose some lines of research to study the potential endocrine mechanisms involved in the effects of agrochemicals on human health and biodiversity.


Subject(s)
Agrochemicals/toxicity , Neurogenesis/drug effects , Animals , Endocrine System/drug effects , Herbicides/toxicity , Humans , Insecticides/toxicity , Pesticides/toxicity
11.
Mol Cell Endocrinol ; 499: 110614, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31606416

ABSTRACT

Bisphenol A (BPA) is a compound used in the polymerization of plastic polycarbonates. It is an endocrine disruptor and it has been postulated to be an obesogen. Our objective was to determine the influence of perinatal exposure to BPA on body weight, hormone levels, metabolic parameters and hypothalamic signals that regulate food intake and kisspeptin system in adult male rats. Male rats were exposed to 50 µg/kg/day of BPA or vehicle from day 9 of gestation to weaning in the drinking water. Since weaning, they were fed with control or high fat diet for 20 weeks. Perinatal exposure to BPA impaired glucose homeostasis, induced obesity and increased food intake in adult male rats altering hypothalamic signals, partially mimicking and/or producing an exacerbation of the effects of feeding fat diet. We also observed an increase in kisspeptin expression by BPA exposure. Evidences shown in this work support the metabolic disruptor hypothesis for BPA.


Subject(s)
Benzhydryl Compounds/adverse effects , Endocrine Disruptors/adverse effects , Kisspeptins/metabolism , Obesity/chemically induced , Phenols/adverse effects , Prenatal Exposure Delayed Effects/metabolism , Animals , Body Weight/drug effects , Diet, High-Fat/adverse effects , Disease Models, Animal , Female , Glucose/metabolism , Male , Obesity/metabolism , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Rats
12.
Neuroscience ; 424: 12-23, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31682820

ABSTRACT

Dopamine is a neurotransmitter crucial for motor, motivational, and reward-related functions. Our aim was to determine the effect of a palatable maternal diet on the transcriptional regulation of dopaminergic-related genes during perinatal development of rat offspring. For that, female offspring from dams fed with a control (CON) or a cafeteria (CAF) diet were sacrificed on embryonic day 21 (E21) and postnatal day 10 (PND10). Using micropunch techniques, ventral tegmental area (VTA) and nucleus accumbens (NAc) were isolated from brain's offspring. Bioinformatic analysis of the promoter regions, mRNA quantification and methylation studies were done. The increase in tyroxine hidroxylase (TH), dopamine receptor (DRD) 1 and ghrelin receptor (GHSR) expression in VTA and NAc from E21 to PND10 was correlated with changes in DNA methylation of their promoter regions. Maternal diet did not affect the expressionpatternsin E21. At PND10, maternal CAF diet decreased the transcription of TH, GHSR, DRD2 and dopamine transporter (DAT) in VTA. Interestingly, the changes in TH, DRD2 and DAT expression were related to the methylation status of their promoters. In NAc, maternal CAF diet reduced DRD1, DRD2 and DAT expression in the offspring at PND10, although alternations in the methylation patterns were only detected in DAT promoter. These results show the importance of maternal nutrition and provide novel insights into the mechanisms through which maternal junk-food feeding can affect reward system during development and early postnatal life. Particularly important is the expression decline of DRD2 given its physiological implication in obesity and addiction.


Subject(s)
Dietary Fats/adverse effects , Dietary Sugars/adverse effects , Epigenesis, Genetic/physiology , Maternal Nutritional Physiological Phenomena/physiology , Nucleus Accumbens/metabolism , Receptors, Dopamine D2/metabolism , Animals , Animals, Newborn , Dietary Fats/administration & dosage , Dietary Sugars/administration & dosage , Dopaminergic Neurons/metabolism , Energy Intake/physiology , Female , Male , Nucleus Accumbens/growth & development , Pregnancy , Rats , Rats, Wistar
13.
Epidemiol Infect ; 147: e216, 2019 01.
Article in English | MEDLINE | ID: mdl-31364547

ABSTRACT

Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.


Subject(s)
Bacterial Proteins/genetics , Drug Resistance, Multiple, Bacterial/genetics , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/genetics , Adolescent , Adult , Age Distribution , Antitubercular Agents/therapeutic use , Brazil/epidemiology , Cost of Illness , DNA-Directed RNA Polymerases/genetics , Databases, Factual , Drug Resistance, Multiple, Bacterial/drug effects , Female , Genotype , Humans , Incidence , Male , Microbial Sensitivity Tests , Middle Aged , Minisatellite Repeats/genetics , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Risk Assessment , Sex Distribution , Tuberculosis, Multidrug-Resistant/drug therapy , Young Adult
14.
Hum Immunol ; 79(9): 659-667, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29913200

ABSTRACT

Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens. We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping. Older kidney transplant recipients demonstrated decreased frequency of naïve CD4+ and CD8+ T cells, and increased frequency of terminally differentiated, immune senescent, and NK T cells expressing KLRG1. There was a trend towards increased frequency of T cell immune senescence in patients experiencing infection in the first year after transplantation, which reached statistical significance in a multivariate analysis. This pilot study reveals immune dysfunction in older compared with younger transplant recipients, and suggests a likely mechanism for increased vulnerability to infection. The ability to assess T cell maturation and immune senescence in transplant recipients offers the potential for risk stratification and customization of immune suppression to prevent infection and rejection after transplantation.


Subject(s)
Graft Rejection/immunology , Kidney Transplantation , Lymphocyte Subsets/physiology , Natural Killer T-Cells/physiology , T-Lymphocytes/physiology , Adult , Age Factors , Aged , Aged, 80 and over , Cell Differentiation , Cellular Senescence , Female , Humans , Immunocompromised Host , Male , Middle Aged , Phenotype , Young Adult
15.
J Endocrinol Invest ; 40(9): 999-1005, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28386795

ABSTRACT

PURPOSE: Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population. METHODS: This observational study included 17 T1DM patients and 17 matched healthy volunteers. Cardiopulmonary exercise test (CPET) was conducted on an electronically-braked cycle ergometer. Blood samples were collected for evaluation of glycemia and lactate levels. RESULTS: Mean oxygen uptake at peak exercise (V'O2,peak) was significantly lower in T1DM subjects (V'O2,peak T1DM 2200 ± 132ml/min vs V'O2,peak Healthy subjects of 2659 ± 120 ml/min p = 0.035). Cardiovascular response analysis did not show statistically significant differences. Respiratory exchange ratio (RER) was significantly higher in healthy subjects at peak exercise and at the first minute of recovery (p = 0.022, p = 0.024). Peak exercise lactate levels were significantly higher in healthy subjects. There was no statistical correlation between CPET results and diabetes-related parameters. CONCLUSIONS: Patients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 1/metabolism , Exercise Test/methods , Exercise Tolerance/physiology , Exercise/physiology , Heart Rate/physiology , Adult , Diabetes Mellitus, Type 1/physiopathology , Female , Humans , Male , Oxygen Consumption/physiology
16.
J Neuroendocrinol ; 28(7)2016 07.
Article in English | MEDLINE | ID: mdl-27306650

ABSTRACT

When steroids, such as pregnenolone, progesterone and oestrogen, are synthesised de novo in neural tissues, they are more specifically referred to as neurosteroids. These neurosteroids bind specific receptors to promote essential brain functions. Pregnenolone supports cognition and protects mouse hippocampal cells against glutamate and amyloid peptide-induced cell death. Progesterone promotes myelination, spinogenesis, synaptogenesis, neuronal survival and dendritic growth. Allopregnanolone increases hippocampal neurogenesis, neuronal survival and cognitive functions. Oestrogens, such as oestradiol, regulate synaptic plasticity, reproductive behaviour, aggressive behaviour and learning. In addition, neurosteroids are neuroprotective in animal models of Alzheimer's disease, Parkinson's disease, brain injury and ageing. Using in situ hybridisation and/or immunohistochemistry, steroidogenic enzymes, including cytochrome P450 side-chain cleavage, 3ß-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase, cytochrome P450arom, steroid 5α-reductase and 3α-hydroxysteroid dehydrogenase, have been detected in numerous brain regions, including the hippocampus, hypothalamus and cerebral cortex. In the present review, we summarise some of the studies related to the synthesis and function of oestrogens and progestagens in the central nervous system.


Subject(s)
Brain/physiology , Brain/physiopathology , Estrogens/physiology , Progestins/physiology , Animals , Brain/enzymology , Brain/metabolism , Estrogens/biosynthesis , Humans , Neuroprotective Agents , Progestins/biosynthesis , Receptors, Neurotransmitter/physiology
17.
Mol Psychiatry ; 21(12): 1752-1767, 2016 12.
Article in English | MEDLINE | ID: mdl-26809838

ABSTRACT

Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of ~20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a 15N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated 15N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration.


Subject(s)
Erythropoietin/metabolism , Neurogenesis/drug effects , Oligodendroglia/drug effects , Animals , Brain/metabolism , Cell Differentiation/drug effects , Cell Differentiation/physiology , Central Nervous System/metabolism , Cognition/drug effects , Hippocampus/metabolism , Hippocampus/physiology , Male , Mice , Mice, Inbred C57BL , Neurogenesis/physiology , Neurons/metabolism , Oligodendroglia/metabolism , Pyramidal Cells/drug effects , Pyramidal Cells/metabolism , Recombinant Proteins/metabolism
18.
Nutr Metab Cardiovasc Dis ; 26(2): 109-13, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26712708

ABSTRACT

BACKGROUND AND AIMS: In a previous study, the single-nucleotide polymorphism (SNP) rs9677, mapped in the 3'-UTR of vasoactive intestinal peptide receptor 1 (VPAC1) gene, was found to be associated with type 2 diabetes (T2D) in Caucasian women. Moreover, the CC genotype correlated with a worse glycolipid profile. The objectives of this study were to confirm this correlation and assess the prevalence of coronary artery disease (CAD) in the previously investigated diabetic women after a follow-up of 4.6 years. METHODS AND RESULTS: A total of 143 women with T2D, with 53 carrying the CC genotype (age: 71.7 ± 7.4 years, diabetes duration: 17.2 ± 9.9 years) and 90 carrying the CT + TT genotypes (age: 69.4 ± 8.8 years, diabetes duration: 14.3 ± 8.2 years), were followed up for 4.6 ± 1.8 years. At follow-up, the clinical and haematochemical parameters were analysed. Twelve-lead electrocardiography, Doppler echocardiography and the percentage of patients with acute myocardial infarction (AMI) or of those subjected to coronary angioplasty and coronary artery bypass surgery were evaluated. At follow-up, there was no significant difference in terms of the clinical and haematochemical parameters between the two groups. However, despite a significantly increased use of statin therapy, no significant improvement in the LDL cholesterol levels was observed in CC female patients unlike those with CT + TT (P = 0.02). Moreover, the CC female patients presented a significantly higher percentage of echocardiographic abnormalities (P = 0.035), especially left ventricular (LV) diastolic dysfunction (P = 0.04). CONCLUSIONS: The rs9677 CC genotype could be correlated with a reduced response to statin therapy and seems to be involved in diabetes cardiomyopathy in female patients with T2D.


Subject(s)
Cholesterol, LDL/blood , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/genetics , Diabetic Angiopathies/genetics , Diabetic Cardiomyopathies/genetics , Dyslipidemias/genetics , Polymorphism, Single Nucleotide , Receptors, Vasoactive Intestinal Polypeptide, Type I/genetics , 3' Untranslated Regions , Aged , Angioplasty, Balloon, Coronary , Biomarkers/blood , Coronary Artery Bypass , Coronary Artery Disease/ethnology , Coronary Artery Disease/physiopathology , Coronary Artery Disease/therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/ethnology , Diabetic Angiopathies/ethnology , Diabetic Angiopathies/physiopathology , Diabetic Angiopathies/therapy , Diabetic Cardiomyopathies/ethnology , Diabetic Cardiomyopathies/physiopathology , Diabetic Cardiomyopathies/therapy , Dyslipidemias/blood , Dyslipidemias/drug therapy , Dyslipidemias/ethnology , Echocardiography, Doppler , Electrocardiography , Female , Follow-Up Studies , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Italy/epidemiology , Middle Aged , Myocardial Infarction/ethnology , Myocardial Infarction/genetics , Myocardial Infarction/physiopathology , Phenotype , Prevalence , Risk Factors , Time Factors , Ventricular Dysfunction, Left/ethnology , Ventricular Dysfunction, Left/genetics , Ventricular Dysfunction, Left/physiopathology , White People/genetics
19.
Clin Ter ; 166(5): e330-4, 2015.
Article in English | MEDLINE | ID: mdl-26550819

ABSTRACT

BACKGROUND AND OBJECTIVES: Previous research has suggest that obesity is associated with increased risk for psychopathological disorders, however, little is known about which obese patients are most vulnerable to psychopathological disorders. We therefore investigated 126 treatment-seeking obese women to describe eating disorder pathology and mental health correlates, and to identify disordered eating behaviors that may place obese at increased risk for psychopathological disorders. MATERIALS AND METHODS: The Structured Clinical Interview for DSM-IV (SCID) was used to identify Eating Disorders (ED). A battery of psychological tests, including the Anxiety Scale Questionnaire (ASQ,) Clinical Depression Questionnaire (CDQ), Eating Disorder Inventory-2 (EDI-2) Eating Attitudes Test-26 (EAT-26) scales and structured clinical interview were administered to all the patients. We analyzed the link between psychopathological disorders and eating attitudes by using both multiple regression analysis and non-parametric correlation. RESULTS: Disordered eating behaviors and emotional behavioral aspects related to Anorexia Nervosa, such as ineffectiveness, are strongly linked to the depression and anxiety in obese subjects. No correlation was found between psychopathological disorders and age or anthropometric measurements. CONCLUSIONS: Findings corroborate earlier work indicating that psychological distress is elevated in obese treatment seeking, bolstering the need for mental health assessment of such individuals. The feeling of ineffectiveness constitutes the major predictor of psychopathological aspects. This is an important result which may inform the development of effective interventions for obese patients and prevention of psychopathological disorders.


Subject(s)
Feeding and Eating Disorders/epidemiology , Mental Health , Obesity/epidemiology , Obesity/psychology , Adult , Aged , Anorexia Nervosa/epidemiology , Anxiety/epidemiology , Depression/epidemiology , Diagnostic and Statistical Manual of Mental Disorders , Feeding Behavior , Female , Humans , Middle Aged , Psychological Tests , Surveys and Questionnaires
20.
Braz. j. med. biol. res ; 47(12): 1016-1020, 12/2014. tab
Article in English | LILACS | ID: lil-727662

ABSTRACT

The diagnostic usefulness of Ziehl-Neelsen (ZN)-stained sputum smears combined with conventional polymerase chain reaction (ZN/PCR) to amplify IS6110 region DNA extracted from ZN slides was evaluated. The objective was to verify if this association could improve tuberculosis (TB) diagnosis in patients at remote sites. The study was carried out in 89 patients with culture-confirmed pulmonary TB as defined by the Brazilian Manual for TB Treatment. The participants were recruited in a reference unit for TB treatment in Rondônia, a state in the Amazonian area in northern Brazil. ZN, PCR, and culture performed in the sputum samples from these patients were analyzed in different combinations (i.e., ZN plus PCR and ZN plus culture). The prevalence rates of pulmonary TB in these patients were 32.6 and 28.1% considering culture and ZN/PCR, respectively. The sensitivity and specificity of ZN/PCR were 86 and 93%, respectively. ZN/PCR was able to detect more TB cases than ZN alone. This method could offer a new approach for accurate tuberculosis diagnosis, especially in remote regions of the world where culture is not available.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , DNA, Bacterial/isolation & purification , Mycobacterium tuberculosis/genetics , Polymerase Chain Reaction/methods , Rainforest , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Brazil/epidemiology , Cross-Sectional Studies , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/growth & development , Prevalence , Sensitivity and Specificity , Staining and Labeling/methods , Tuberculosis, Pulmonary/epidemiology
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