scholarly journals 17β-Estradiol Modulates Expression of Low-Voltage-Activated CaV3.2 T-Type Calcium Channel via Extracellularly Regulated Kinase Pathway in Cardiomyocytes

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 879-888 ◽  
Author(s):  
Farzana Marni ◽  
Yan Wang ◽  
Masaki Morishima ◽  
Toru Shimaoka ◽  
Tomoko Uchino ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Low Voltage ◽  
Heart Diseases ◽  
Ovariectomized Rats ◽  
Pacemaker Activity ◽  
Short Term ◽  
Channel Current ◽  
Long Term Treatment ◽  
17Β Estradiol

T-type Ca2+ channel current (ICa,T) plays an important role for spontaneous pacemaker activity and is involved in the progression of structural heart diseases. Estrogens are of importance for the regulation of growth and differentiation and function in a wide array of target tissues, including those in the cardiovascular system. The aim of this study was to elucidate the short-term and long-term effects of 17β-estradiol (E2) on ICa,T in cardiomyocytes. We employed in vivo and in vitro techniques to clarify E2-mediated modulation of heart rate (HR) in ovariectomized rats and ICa,T in cardiomyocytes. Ovariectomy increased HR and E2 supplement reduced HR in ovariectomized rats. Slowing of E2-induced HR was consistent with the deceleration of automaticity in E2-treated neonatal cardiomyocytes. Short-term application of E2 did not have significant effects on ICa,T, whereas in cardiomyocytes treated with 10 nm E2 for 24 h, estrogen receptor-independent down-regulation of peak ICa,T and declination of CaV3.2 mRNA were observed. Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also suppressed by E2 treatment for 24 h. On the other hand, expression of CaV3.1 mRNA was unaltered by E2 treatment in this study. An ERK-1/2, 5 inhibitor, PD-98059, abolished the effects of E2 on ICa,T and CaV3.2 mRNA as well as Csx/Nkx2.5 mRNA. These findings indicate that E2 decreases CaV3.2 ICa,T through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E2 as a negative chronotropic factor in the heart. Long-term treatment of cardiomyocytes with 17β-estradiol decreases the T-type Ca2+ channel current of CaV3.2 through activation of ERK-1/2, 5, which is mediated by the suppression of a transcription factor Csx/Nkx2.5.

Fluvoxamine in the Treatment of Trichotillomania: An 8-Week, Open-Label Study

CNS Spectrums ◽  
1998 ◽  
Vol 3 (9) ◽  
pp. 64-71 ◽  
Author(s):  
Gary A. Christenson ◽  
Scott J. Crow ◽  
James E. Mitchell ◽  
Thomas B. Mackenzie ◽  
Ross D. Crosby ◽  
...  
Keyword(s):  
Treatment Response ◽  
Term Treatment ◽  
Hair Pulling ◽  
Short Term ◽  
Open Label ◽  
Short Term Treatment ◽  
Open Label Study ◽  
Label Study ◽  
Long Term Treatment

AbstractThis short-term, open-label study investigates short- and long-term effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine for the treatment of trichotillomania (TTM). Additionally, this study aimed to test the hypothesis that the presence of hair pulling compulsiveness is predictive of SSRI response. Nineteen subjects meeting the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, (DSM-III-R) criteria for TTM were treated with fluvoxamine at doses up to 300 mg/day. Random regression analysis of change across time for patients who completed the study (n=14) and those who dropped out (n=5) revealed statistically significant improvements in Physician Rating Scale, hair-pulling episodes, Trichotillomania Impairment Scale, and Trichotillomania Symptom Severity Scale, but not in estimated amount of hair pulled. In addition, the percentage of patients' focused or compulsive hair-pulling symptoms was predictive of treatment response. Unfortunately, all three subjects who entered long-term treatment displayed substantial movement back toward baseline by the end of 6 months. We concluded that fluvoxamine produces moderate reductions in symptoms during the short-term treatment of TTM and that the presence of focused or compulsive hair pulling may be predictive of treatment response. However, responses may be short lived when treatment is extended.

scholarly journals Nonmedical Interventions for Schizophrenia: A Review of Diet, Exercise and Social Roles

2020 ◽  
Author(s):  
Daniel S. Helman
Keyword(s):  
Term Treatment ◽  
Physical Processes ◽  
Dietary Interventions ◽  
Short Term ◽  
Alternative Interventions ◽  
Social Interventions ◽  
General Utility ◽  
Long Term Treatment ◽  
Abnormal Lipid Metabolism

Schizophrenia is a major mental illness with a disease course that is influenced by lifestyle. The risk-benefit ratio for alternative interventions is more favorable than for antipsychotics in long-term treatment. Dietary interventions may target autoimmune features, vitamin or mineral deficiencies, abnormal lipid metabolism, gluten sensitivity or others. Examples of interventions involving diet, physical activity or physical processes, or social interventions including talk therapy exist in the literature. Notwithstanding, the general utility of these types of interventions remains inconclusive, awaiting long-term randomized trials. A perspective that separates the cause of the disease from its symptoms may be helpful in treatment planning and is warranted to distinguish between short-term and long-term recovery goals.

scholarly journals A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Aimee Iberg-Badeaux ◽  
Samuel Collombet ◽  
Benoit Laurent ◽  
Chris van Oevelen ◽  
Kuo-Kai Chin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Short Term Memory ◽  
Epigenetic Mechanism ◽  
Short Term ◽  
Term Memory ◽  
Pol Ii ◽  
Transcriptional Memory

ABSTRACT Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in postmitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for long-term transcriptional memory (LTTM) and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) induces LTTM on a subset of target genes that survives nine cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed than at those genes that do not exhibit memory, akin to a latent state. We show through chromatin immunoprecipitation (ChIP) and chemical inhibitor studies that RNA polymerase II (Pol II) elongation is important for establishing memory in this model but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM and that failure to rerepress chromatin is one epigenetic mechanism underlying transcriptional memory.

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

A Review of Metabolic Parameters in Quetiapine Studies Across Diagnoses

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Newcomer ◽  
R. Ratner ◽  
M. Åström ◽  
H. Eriksson
Keyword(s):  
Atypical Antipsychotics ◽  
Extended Release ◽  
Term Treatment ◽  
Metabolic Parameters ◽  
Short Term ◽  
Pooled Data ◽  
Long Term Treatment ◽  
Potential Risks ◽  
The Difference

Background:Data pertaining to changes in weight during long-term treatment with quetiapine (QTP) have been published previously (1).Methods:Pooled data are presented from 26 short-term clinical studies (up to 12 weeks) of QTP or quetiapine extended-release (QTP XR)-as monotherapy or adjunct therapy-conducted by AstraZeneca up to November 2007. Studies were conducted in adult patients (18-65 years) across a number of psychiatric diagnoses. Variables were analyzed irrespective of fasting status with similar analyses planned in the fasting subset. LSM changes from baseline for the difference between QTP and placebo are presented.Results:Approximately 10000 patients were included in the analyses, 70% of whom were treated with QTP or QTP XR. Across the entire short-term dataset, the difference in LSM change in weight for QTP vs. placebo was 1.07 kg. Corresponding differences in glucose regulation parameters were 1.39 mg/dL for glucose and 0.04% units for HbA1C. the overall difference in total cholesterol was 5.48 mg/dL, with differences in HDL and LDL cholesterol of -0.62 mg/dL and 1.69 mg/dL. the difference in LSM change in triglycerides was 22.62 mg/dL.Discussion:Within the context of balancing potential risks against the acknowledged benefits of atypical antipsychotics, the degree and significance of variations in metabolic parameters is an area of continued interest. This analysis helps clinicians to better understand changes in important metabolic parameters across trials with QTP and QTP XR, and the size and uniqueness of the dataset permits further analyses within this important area.Supported by funding from AstraZeneca Pharmaceuticals LP.

scholarly journals Protein Metabolism in Acromegaly: Differential Effects of Short- and Long-Term Treatment

2007 ◽  
Vol 92 (4) ◽  
pp. 1479-1484 ◽  
Author(s):  
James Gibney ◽  
Troels Wolthers ◽  
Morton G. Burt ◽  
Kin-Chuen Leung ◽  
A. Margot Umpleby ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Protein Metabolism ◽  
Normal Subjects ◽  
Term Treatment ◽  
Protein Breakdown ◽  
Short Term ◽  
Leucine Oxidation ◽  
Long Term Treatment ◽  
Short And Long Term

Abstract Context: GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation. Objective: The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction. Design: We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n = 8) or long-term (n = 10) treatment. Setting: The study was conducted at a clinical research center. Main Outcome Measures: Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured. Results: Leucine Ra and NOLD were greater (P &lt; 0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P &lt; 0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P &lt; 0.05) after short- and long-term treatment. Adjustment for body composition did not affect results. Conclusions: In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.

Lurasidone and risk for metabolic syndrome: results from short- and long-term clinical studies in patients with schizophrenia

CNS Spectrums ◽  
2020 ◽  
pp. 1-11
Author(s):  
Michael Tocco ◽  
John W. Newcomer ◽  
Yongcai Mao ◽  
Andrei Pikalov ◽  
Antony Loebel
Keyword(s):  
Metabolic Syndrome ◽  
Dose Range ◽  
Dose Effect ◽  
Short Term ◽  
Open Label ◽  
Quetiapine Xr ◽  
Long Term Treatment ◽  
Short And Long Term ◽  
Term Data

Abstract Objective To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia. Methods Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone. Results MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone. Conclusion In this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).

INFLUENCE OF GONADAL HORMONES ON THE ACTION OF CALCITONIN IN THE RAT

1971 ◽  
Vol 68 (3) ◽  
pp. 585-596 ◽  
Author(s):  
O. Helmer Serensen ◽  
Inge Hindberg
Keyword(s):  
Serum Calcium ◽  
Thyroid Tissue ◽  
Gonadal Hormones ◽  
Term Treatment ◽  
Female Rats ◽  
Short Term ◽  
Oestrogen Treatment ◽  
Male And Female Rats ◽  
Long Term Treatment

ABSTRACT The influence of short-term and long-term treatment with gonadal hormones on the response to calcitonin was investigated in the rat. Oestrogen-treatment, short-term as well as long-term, resulted in a reduced responsiveness to calcitonin. Long-term treatment with androgens enhanced the hypocalcaemic effect of calcitonin in castrated rats of either sex, but reduced the effect in intact animals. No sex differences could be registered in the sensitivity to calcitonin, when intact animals were compared according to age, while marked differences were observed, when the animals were compared according to weight. There was a linear decrease in the response to calcitonin with increasing age in rats of both sexes. An intraperitoneal calcium load was followed by an acute rise in the serum calcium levels. The adult animals counteracted the hypercalcaemia more slowly than the young ones. Significant differences also occurred between male and female rats, the rise in the serum calcium concentration being much more pronounced in the latter group. The hypocalcaemic activity of thyroid tissue from rats of both sexes and of various ages showed considerable variations, but no differences correlated to age or sex.

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