Редактирование: BID (раздел)

==Publications==

{{medline-entry
|title=Dabigatran etexilate: appropriate use in patients with chronic kidney disease and in the elderly patients.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28439778
|abstract=Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations. Patients with AF and chronic kidney disease (CKD) are per se at high risk of stroke, bleeding and mortality. Although there is evidence of clinical benefit of anticoagulation in these patients, anticoagulant therapy requires caution and demands careful clinical monitoring, regardless of the drug used. In patients with no contraindication to its use, the clinical benefit of DE versus warfarin is independent of renal function. The elderly with AF are frequently undertreated because of the perception of high bleeding risk and limited clinical benefit. However, the clinical benefit of anticoagulation is independent of patient age, and age per se should not represent a contraindication to anticoagulation. DE has been extensively studied in the elderly, both in randomized clinical trials and in observational studies: DE 150 mg [[BID]] should not be used in patients 80 years of age or older, while DE 110 mg [[BID]] is as safe as warfarin. Intracranial haemorrhages reduction by DE compared with warfarin is preserved in the elderly. Therefore, mild and moderate CKD and being elderly should not deter physicians from prescribing DE. Furthermore, the availability of a specific antidote is expected to improve the safety of the use of DE in clinical practice.
|mesh-terms=* Aged
* Aged, 80 and over
* Anticoagulants
* Antithrombins
* Atrial Fibrillation
* Dabigatran
* Geriatrics
* Hemorrhage
* Humans
* Metabolic Clearance Rate
* Renal Insufficiency, Chronic
* Warfarin
|keywords=* Bleeding
* Chronic kidney disease
* Dabigatran
* Elderly
|full-text-url=https://sci-hub.do/10.1007/s11739-017-1660-6
}}
{{medline-entry
|title=Sperm-associated antigen 9 ([[SPAG9]]) promotes the survival and tumor growth of triple-negative breast cancer cells.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27449044
|abstract=Recently, we demonstrated the association of sperm-associated antigen 9 ([[SPAG9]]) expression with breast cancer. Among breast cancer, 15 % of the cancers are diagnosed as triple-negative breast cancers (TNBC) based on hormone receptor status and represent an important clinical challenge because of lack of effective available targeted therapy. Therefore, in the present investigation, plasmid-based small hairpin (small hairpin RNA (shRNA)) approach was used to ablate [[SPAG9]] in aggressive breast cancer cell line model (MDA-[[MB]]-231) in order to understand the role of [[SPAG9]] at molecular level in apoptosis, cell cycle, and epithelial-to-mesenchymal transition (EMT) signaling. Our data in MDA-[[MB]]-231 cells showed that ablation of [[SPAG9]] resulted in membrane blebbing, increased mitochondrial membrane potential, DNA fragmentation, phosphatidyl serine surface expression, and caspase activation. [[SPAG9]] depletion also resulted in cell cycle arrest in G0-G1 phase and induced cellular senescence. In addition, in in vitro and in vivo xenograft studies, ablation of [[SPAG9]] resulted in upregulation of p21 along with pro-apoptotic molecules such as BAK, [[BAX]], BIM, [[BID]], NOXA, AIF, Cyto-C, [[PARP1]], [[APAF1]], Caspase 3, and Caspase 9 and epithelial marker, E-cadherin. Also, [[SPAG9]]-depleted cells showed downregulation of cyclin B1, cyclin D1, cyclin E, [[CDK1]], [[CDK4]], [[CDK6]], [[BCL2]], Bcl-xL, [[XIAP]], cIAP2, [[MCL1]], GRP78, SLUG, SNAIL, TWIST, vimentin, N-cadherin, [[MMP2]], [[MMP3]], [[MMP9]], SMA, and β-catenin. Collectively, our data suggests that [[SPAG9]] promotes tumor growth by inhibiting apoptosis, altering cell cycle, and enhancing EMT signaling in in vitro cells and in vivo mouse model. Hence, [[SPAG9]] may be a potential novel target for therapeutic use in TNBC treatment.
|mesh-terms=* Adaptor Proteins, Signal Transducing
* Animals
* Apoptosis
* Blotting, Western
* Cell Proliferation
* Fluorescent Antibody Technique, Indirect
* Humans
* Immunoenzyme Techniques
* Membrane Potential, Mitochondrial
* Mice
* RNA, Small Interfering
* Triple Negative Breast Neoplasms
* Tumor Cells, Cultured
|keywords=* Apoptosis
* Cell growth
* Cellular motility
* SPAG9
* Senescence
* Triple-negative breast cancer
* Tumor growth
|full-text-url=https://sci-hub.do/10.1007/s13277-016-5240-6
}}
{{medline-entry
|title=Rationale for the Assessment of Metoprolol in the Prevention of Vasovagal Syncope in Aging Subjects Trial (POST5).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26995374
|abstract=Vasovagal syncope (VVS) is a common problem associated with a poor quality of life, which improves when syncope frequency is reduced. Effective pharmacological therapies for VVS are lacking. Metoprolol is a β-adrenergic receptor antagonist that is ineffective in younger patients, but may benefit older (≥40 years) VVS patients. Given the limited therapeutic options, a placebo-controlled clinical trial of metoprolol for the prevention of VVS in older patients is needed. The POST5 is a multicenter, international, randomized, placebo-controlled study of metoprolol in the prevention of VVS in patients ≥40 years old. The primary endpoint is the time to first recurrence of syncope. Patients will be randomized 1:1 to receive metoprolol 25 to 100 mg [[BID]] or matching placebo, and followed up for 1 year. Secondary end points include syncope frequency, presyncope, quality of life, and cost analysis. Primary analysis will be intention to treat, with a secondary on-treatment analysis. A sample size of 222, split equally between the groups achieves 85% power to detect a hazard rate of 0.3561 when the event rates are 50% and 30% in the placebo and metoprolol arms. Allowing for 10% dropout, we propose to enroll 248 patients. This study will be the first adequately powered trial to determine whether metoprolol is effective in preventing VVS in patients ≥40 years. If effective, metoprolol may become the first line pharmacological therapy for these patients.
|mesh-terms=* Administration, Oral
* Adrenergic beta-Antagonists
* Adult
* Aged
* Aging
* Dose-Response Relationship, Drug
* Double-Blind Method
* Female
* Follow-Up Studies
* Humans
* Male
* Metoprolol
* Middle Aged
* Prospective Studies
* Quality of Life
* Recurrence
* Syncope, Vasovagal
* Time Factors
* Treatment Outcome

|full-text-url=https://sci-hub.do/10.1016/j.ahj.2016.01.017
}}
{{medline-entry
|title=The geriatric mania asenapine study (GeMS).
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26952385
|abstract=Population aging results in growing numbers of psychiatric disorders among older patients. Yet, there is a paucity of studies on elderly mania. To evaluate the effect of asenapine on older manic inpatients. Thirty-four elderly patients suffering from a manic episode, mean age 67.2 years were enrolled in an open-label 3-weeks study of asenapine treatment. (1) DSM-IV criteria for manic episode (2) age above 60 years, (3) episode severity necessitating inpatient treatment, (4) Young Mania Rating Scale (YMRS) score at baseline >20, and (5) no prior asenapine treatment. Participants were prescribed asenapine 5 mg [[BID]] for 3 days and then dose increased to 10 mg [[BID]] till day 21 (study completion). Twenty-five patients completed the study. YMRS score decreased from a baseline mean of 27.0±8.8 to 13.3±12.0 at the end of the study (p<0.001). Fourteen patients (56% of completers) achieved remission (YMRS score<12). MADRS score decreased from a baseline mean of 7.6±5.6 to 4.4 5.1 at the end of the study (p<0.05); low baseline score should be noted. Sleep duration increased from a baseline median of 5.7 hours to 7.0 h at the end of the study (p<0.05). Seven patients discontinued treatment due to adverse events. Two patients passed-away after study completion. We tentatively conclude that the efficacy of asenapine in reducing acute manic symptoms and achieving remission in the elderly is supported in this study. Caution is needed in patients with co-morbid physical conditions.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Antipsychotic Agents
* Bipolar Disorder
* Female
* Heterocyclic Compounds, 4 or More Rings
* Hospitalization
* Humans
* Inpatients
* Male
* Middle Aged
* Physical Examination
* Psychiatric Status Rating Scales
* Treatment Outcome
|keywords=* Asenapine
* Elderly
* Mania
|full-text-url=https://sci-hub.do/10.1016/j.archger.2016.01.012
}}
{{medline-entry
|title=The effect of aging on mitochondrial and cytosolic hepatic intrinsic death pathway and apoptosis associated proteins in Fischer 344 rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25910621
|abstract=Apoptosis is increased in the liver in old age and is a common pathological feature of liver disease. The mitochondria play a key role in regulating apoptosis via the intrinsic death pathway. As the effect of aging on this pathway is unclear, we aimed to characterize the impact of aging on the hepatic intrinsic death pathway and apoptosis. Livers from young adult (6.6 ± 0.3 months, n = 9) and old (25.4 ± 0.7 months, n = 9) male Fischer 344 rats were extracted for cellular fractionation and immunobloting. In old age there were lower mitochondrial protein levels of pro-apoptotic BAK, [[BID]], t[[BID]] and [[VDAC1]] (p < 0.05) and of anti-apoptotic Bcl-2. Compared to young, old rats had lower cytosolic protein levels of pro-apoptotic [[BAX]], BAK, [[BID]], t[[BID]] and anti-apoptotic Bcl-xL (p < 0.05). BAK, Bcl-2 and Bcl-xL were found in the cytosol. Furthermore with old age, cytosolic protein levels of cytochrome C, AIF and cleaved caspase-9 did not change but activation of caspase-3, -6 and -7 increased (p < 0.05) and DNA fragmentation trended to increase. Our results suggest an age-related decline in the levels of a number of proteins involved in the intrinsic death pathway, an uncoupling of intermediate apoptosis signaling and increased cellular apoptosis in the liver in old age.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Apoptosis Regulatory Proteins
* Cytosol
* Liver
* Male
* Mitochondria, Liver
* Mitochondrial Proteins
* Rats, Inbred F344
|keywords=* Aging
* Apoptosis
* Intrinsic death pathway
* Liver
* Mitochondria
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854160
}}
{{medline-entry
|title=Neuroimmunomodulation and aging: a role for transferrin and the hypothalamus/thymus axis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23895519
|abstract=Advanced age is associated with an increased incidence of immune and degenerative disorders, mediated by metabolic changes, dysregulation of proinflammatory signals, and apoptosis. Concurrently, there is a progressive decline in self-recognition. Investigations on biologic functions of transferrin (Tf) other than iron transport showed that Tf has a profound cytoprotective (anti-apoptotic) effect on lympho-hematopoietic cells and the thymus, and interferes with stress-induced signals. Tf protects hepatocytes against Fas-induced cell death by reducing [[BID]] cleavage, inhibiting caspase-3 and -9 activation and up-regulating survival signals such as Bcl-xL. The involvement in the regulation of alloreactivity and apoptosis suggests that Tf participates in the maintenance of "self-identity" mechanisms, which are tightly linked to the capacity of the immune system to recognize and react against any noxious agent. Some of the disorders associated with aging are thought to be related to thymic involution, reflecting alterations in the interplay of neural, endocrine and immune factors. We established a murine model of thymic involution induced by stereotactically placed electrolytic lesions in the anterior hypothalamic area. The events observed in this model mimic those observed during senescence including thymus involution, i.e. enhanced glucocorticoid reaction to distress, and obesity. The described properties of Tf can be exploited to modify immune responses and provide cytoprotection against pro-apoptotic and cytotoxic signals when neuroimmunomodulatory mechanisms are impaired, as is the case with aging.
|mesh-terms=* Aging
* Animals
* Apoptosis
* Cytokines
* Humans
* Hypothalamus
* Inflammation Mediators
* Liver
* Mice
* Models, Immunological
* Models, Neurological
* Neuroimmunomodulation
* Receptors, Transferrin
* Self Tolerance
* Signal Transduction
* Thymus Gland
* Transferrin

|full-text-url=https://sci-hub.do/10.2174/1874609811306010004
}}
{{medline-entry
|title=Pharmacokinetics, safety, and tolerability of the new antiepileptic carisbamate in the elderly.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18280116
|abstract=To evaluate the effect of age on the disposition of two different oral formulations of carisbamate (RWJ-333369), a novel neuromodulator under investigation. The disposition of carisbamate was studied in eight men and eight women in each of the three age groups: 18-55, 65-74, and >or= 75 years (N=48). Subjects received single (100mg immediate-release [IR] tablets or 250 mg controlled-release [CR] tablets) or repeated administration (up to 500 mg IR [[BID]] or 1250 mg CR QD) of carisbamate in a randomized, double-blind, placebo-controlled, parallel-group, single-center study. After either single or repeated IR administration, no apparent differences were observed between the two elderly and the non-elderly groups. Following single-dose CR administration, the two elderly age groups had higher exposure compared with non-elderly subjects, but the difference decreased for all doses tested after repeated administration. There was no effect of age on plasma protein binding of carisbamate. Renal clearance decreased with age for both formulations, but this decrease had no effect on the total clearance of the drug because of its limited renal elimination. Age had no effect on pharmacokinetics of carisbamate IR formulation. The small effect observed after single-dose CR carisbamate diminished after repeated dosing. The drug was generally safe and well tolerated.
|mesh-terms=* Administration, Oral
* Adult
* Age Factors
* Aged
* Aging
* Anticonvulsants
* Area Under Curve
* Carbamates
* Confidence Intervals
* Dose-Response Relationship, Drug
* Double-Blind Method
* Drug Administration Schedule
* Drug Evaluation
* Drug Tolerance
* Female
* Humans
* Male
* Middle Aged

|full-text-url=https://sci-hub.do/10.1016/j.eplepsyres.2007.12.013
}}
{{medline-entry
|title=Societal influences on body image dissatisfaction in younger and older women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16635949
|abstract=Few studies have examined older women's body image. This study compared body image dissatisfaction ([[BID]]) and weight control practices; evaluated associations among [[BID]], societal influences and concern for appropriateness (CFA); and identified the most important correlate of [[BID]] among younger (19-23) and older women (65-74). Questionnaires obtained information on demographics, weight control practices, societal influences (SATAQ-3), CFA and [[BID]] using the Figure Rating Scale. Findings revealed no difference in the prevalence of [[BID]]. The number of weight control practices and SATAQ-3 and CFA scores were correlated to [[BID]]. Pressure from the media was the most significant correlate of [[BID]].
|mesh-terms=* Adult
* Aged
* Aging
* Body Image
* Body Mass Index
* Body Weight
* Cross-Sectional Studies
* Female
* Humans
* Internal-External Control
* Obesity
* Personal Satisfaction
* Self Concept
* Social Conformity
* Social Desirability
* Social Support
* Surveys and Questionnaires

|full-text-url=https://sci-hub.do/10.1300/J074v18n01_04
}}
{{medline-entry
|title=Association between patient age and gabapentin serum concentration-to-dose ratio: a preliminary multivariate analysis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/15570187
|abstract=To evaluate the association between patient age and gabapentin (GBP) concentration-to-dose ratio by a multivariate analysis. The association between patient age and the trough steady-state serum concentration of gabapentin (GBP) normalized to 1 mg/kg body weight or concentration-to-dose ratio (CDR) was retrospectively assessed by analysis of covariance. Potential confounding factors considered were GBP dosage, the number of GBP doses per day, and the presence of concomitant antiepileptic drugs (AEDs). Concentrations that had been measured in predose "trough" samples collected from 66 patients, aged 5-84 years, with partial seizures or neuropathic pain chronically receiving GBP [[BID]] (n = 21) or TID (n = 45), alone (n = 15) or in combination with other AEDs (n = 51) were used in this retrospective analysis. Average GBP CDR was 0.23  /- 0.18 (mean  /- SD). The GBP CDR increased with age (r2 = 0.46, P < 0.001), and the correlation was improved when only samples from patients taking GBP [[BID]] were separately considered (r2 = 0.68, P < 0.001). The ratio was lower in the 10 children younger than 11 years of age (0.07  /- 0.05) than in 8 adolescents aged 12 to 18 years (0.14  /- 0.04), lower than in 35 adults aged 19 to 65 years (0.22  /- 0.13), and lower than in 13 patients older than 65 years of age (0.45  /- 0.20) by 1-way analysis of variance (F = 19.4, P < 0.001). Analysis of covariance showed a significant influence on GBP CDR of patient age (P < 0.001) and the number of GBP daily doses (P < 0.01), but GBP daily dosage or concomitant AEDs had no significant influence on the ratio. In this retrospective study of a small, select group of patients, (1) the GBP CDR increased significantly with age when potential confounding factors such as GBP dosage, number of GBP doses per day, and concomitant AEDs were considered by analysis of covariance, and (2) patients older than 65 years, even without any known renal disease, may have double GBP CDR than younger adults and, therefore, may need half of the GBP dose per body weight to achieve a similar concentration.
|mesh-terms=* Adolescent
* Adult
* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Amines
* Analysis of Variance
* Child
* Child, Preschool
* Cyclohexanecarboxylic Acids
* Dose-Response Relationship, Drug
* Female
* Gabapentin
* Humans
* Male
* Middle Aged
* Multivariate Analysis
* Retrospective Studies
* gamma-Aminobutyric Acid

|full-text-url=https://sci-hub.do/10.1097/00007691-200412000-00008
}}
{{medline-entry
|title=Comparison of telithromycin, a new ketolide, with erythromycin and clarithromycin for the treatment of Haemophilus influenzae pneumonia in suckling, middle aged and senescent mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12385696
|abstract=We studied the efficacy of telithromycin in Haemophilus influenzae pneumoniae in three different age groups of mice. Pneumonia was produced by endotracheal instillation of 1 x 10(4) CFU/ml of bacteria and treatment was initiated with saline for control and compared with two different doses, 50 and 100 mg/kg per [[BID]] telithromycin twice a day for 1 week. For comparison, we used erythromycin (ERY) and clarithromycin (CLA), both given twice a day at 50 mg/kg per [[BID]]. Some animals were euthanized on the third or 7th day of therapy and their lung tissue was cultured for bacteria. Presence of bacteria was considered a failure and a sterile lung was considered cured. As expected, about one half of middle-aged animals (8-10 months) were cured on saline. In contrast, almost none of the young (2-3 weeks) and old animals (18-20 months) were cured without antibiotic therapy. Among the young, the cure rates with telithromycin, ERY and CLA were 81, 50 and 33%, respectively. Of the senescent mice, the cure rate with ERY was 50% whereas the rates with CLA and telithromycin (50 mg/kg) were 62 and 75%, respectively. In conclusion, telithromycin is effective against H. influenzae at both extremes of life.
|mesh-terms=* Aging
* Animals
* Animals, Suckling
* Anti-Bacterial Agents
* Area Under Curve
* Clarithromycin
* Drug Administration Schedule
* Drug Evaluation, Preclinical
* Erythromycin
* Haemophilus influenzae
* Ketolides
* Lung
* Macrolides
* Mice
* Pneumonia, Bacterial
* Tissue Distribution

|full-text-url=https://sci-hub.do/10.1016/s0924-8579(02)00176-0
}}