scholarly journals Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Cristóbal-García ◽  
Fernando E. García-Arroyo ◽  
Edilia Tapia ◽  
Horacio Osorio ◽  
Abraham S. Arellano-Buendía ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Renal Cortex ◽  
Systemic Hypertension ◽  
Tubular Damage ◽  
Short Term ◽  
Mitochondrial Alterations ◽  
Atp Levels ◽  
Long Term Treatment

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

scholarly journals Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Carmina Silaidos ◽  
Jens Zotzel ◽  
Stefan Marx ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Citrate Synthase ◽  
Brain Aging ◽  
Mrna Levels ◽  
Nmri Mice ◽  
Aged Mice ◽  
Atp Levels ◽  
Long Term Treatment ◽  
The Brain

Aging represents a major risk factor for developing neurodegenerative diseases such as Alzheimer’s disease (AD). As components of the Mediterranean diet, olive polyphenols may play a crucial role in the prevention of AD. Since mitochondrial dysfunction acts as a final pathway in both brain aging and AD, respectively, the effects of a mixture of highly purified olive secoiridoids were tested on cognition and ATP levels in a commonly used mouse model for brain aging. Over 6 months, female NMRI mice (12 months of age) were fed with a blend containing highly purified olive secoiridoids (POS) including oleuropein, hydroxytyrosol and oleurosid standardized for 50 mg oleuropein/kg diet (equivalent to 13.75 mg POS/kg b.w.) or the study diet without POS as control. Mice aged 3 months served as young controls. Behavioral tests showed deficits in cognition in aged mice. Levels of ATP and mRNA levels of NADH-reductase, cytochrome-c-oxidase, and citrate synthase were significantly reduced in the brains of aged mice indicating mitochondrial dysfunction. Moreover, gene expression of Sirt1, CREB, Gap43, and GPx-1 was significantly reduced in the brain tissue of aged mice. POS-fed mice showed improved spatial working memory. Furthermore, POS restored brain ATP levels in aged mice which were significantly increased. Our results show that a diet rich in purified olive polyphenols has positive long-term effects on cognition and energy metabolism in the brain of aged mice.

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 Putative role of pharmacogenetics to elucidate the mechanism of tardive dyskinesia in schizophrenia

2019 ◽  
Vol 20 (17) ◽  
pp. 1199-1223 ◽  
Author(s):  
Anton JM Loonen ◽  
Bob Wilffert ◽  
Svetlana A Ivanova
Keyword(s):  
Oxidative Stress ◽  
Tardive Dyskinesia ◽  
Genetic Variants ◽  
Long Term Potentiation ◽  
Specific Gene ◽  
Medium Spiny Neurons ◽  
Spiny Neurons ◽  
Long Term Treatment

Identifying biomarkers which can be used as a diagnostic tool is a major objective of pharmacogenetic studies. Most mental and many neurological disorders have a compiled multifaceted nature, which may be the reason why this endeavor has hitherto not been very successful. This is also true for tardive dyskinesia (TD), an involuntary movement complication of long-term treatment with antipsychotic drugs. The observed associations of specific gene variants with the prevalence and severity of a disorder can also be applied to try to elucidate the pathogenesis of the condition. In this paper, this strategy is used by combining pharmacogenetic knowledge with theories on the possible role of a dysfunction of specific cellular elements of neostriatal parts of the (dorsal) extrapyramidal circuits: various glutamatergic terminals, medium spiny neurons, striatal interneurons and ascending monoaminergic fibers. A peculiar finding is that genetic variants which would be expected to increase the neostriatal dopamine concentration are not associated with the prevalence and severity of TD. Moreover, modifying the sensitivity to glutamatergic long-term potentiation (and excitotoxicity) shows a relationship with levodopa-induced dyskinesia, but not with TD. Contrasting this, TD is associated with genetic variants that modify vulnerability to oxidative stress. Reducing the oxidative stress burden of medium spiny neurons may also be the mechanism behind the protective influence of 5-HT2 receptor antagonists. It is probably worthwhile to discriminate between neostriatal matrix and striosomal compartments when studying the mechanism of TD and between orofacial and limb-truncal components in epidemiological studies.

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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