scholarly journals Expression of Longevity Genes Induced by a Low-Dose Fluvastatin and Valsartan Combination with the Potential to Prevent/Treat “Aging-Related Disorders”

2019 ◽  
Vol 20 (8) ◽  
pp. 1844 ◽  
Author(s):  
Miodrag Janić ◽  
Mojca Lunder ◽  
Srdjan Novaković ◽  
Petra Škerl ◽  
Mišo Šabovič
Keyword(s):  
Low Dose ◽  
Telomerase Activity ◽  
Treatment Discontinuation ◽  
Placebo Control ◽  
Middle Aged ◽  
Beneficial Effects ◽  
Genes Expression ◽  
Longevity Genes ◽  
Before And After ◽  
Stored Blood

The incidence of aging-related disorders may be decreased through strategies influencing the expression of longevity genes. Although numerous approaches have been suggested, no effective, safe, and easily applicable approach is yet available. Efficacy of low-dose fluvastatin and valsartan, separately or in combination, on the expression of the longevity genes in middle-aged males, was assessed. Stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin-valsartan combination (10 and 20 mg, respectively), and placebo (control) were analyzed. They were taken before and after 30 days of treatment and, additionally, five months after treatment discontinuation. The expression of the following longevity genes was assessed: SIRT1, PRKAA, KLOTHO, NFE2L2, mTOR, and NF-κB. Treatment with fluvastatin and valsartan in combination significantly increased the expression of SIRT1 (1.8-fold; p < 0.0001), PRKAA (1.5-fold; p = 0.262) and KLOTHO (1.7-fold; p < 0.0001), but not NFE2L2, mTOR and NF-κB. Both fluvastatin and valsartan alone significantly, but to a lesser extent, increased the expression of SIRT1, and did not influence the expression of other genes. Five months after treatment discontinuation, genes expression decreased to the basal levels. In addition, analysis with previously obtained results revealed significant correlation between SIRT1 and both increased telomerase activity and improved arterial wall characteristics. We showed that low-dose fluvastatin and valsartan, separately and in combination, substantially increase expression of SIRT1, PRKAA, and KLOTHO genes, which may be attributed to their so far unreported pleiotropic beneficial effects. This approach could be used for prevention of ageing (and longevity genes)–related disorders.

Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through Telomerase Activity Increase in Middle-Aged Men

2016 ◽  
Vol 19 (2) ◽  
pp. 115-119 ◽  
Author(s):  
Miodrag Janić ◽  
Mojca Lunder ◽  
Petra Cerkovnik ◽  
Uršula Prosenc Zmrzljak ◽  
Srdjan Novaković ◽  
...  
Keyword(s):  
Arterial Wall ◽  
Low Dose ◽  
Telomerase Activity ◽  
Middle Aged ◽  
Activity Increase

scholarly journals No change in the consumption of thyroid hormones after starting low dose naltrexone (LDN): a quasi-experimental before-after study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Guttorm Raknes ◽  
Lars Småbrekke
Keyword(s):  
Thyroid Hormones ◽  
Low Dose ◽  
Prescription Database ◽  
Beneficial Effects ◽  
Defined Daily Doses ◽  
Before And After ◽  
Quasi Experimental ◽  
Norwegian Prescription Database ◽  
Study Participants ◽  
Low Dose Naltrexone

Abstract Background Low dose naltrexone (LDN) is reported to have beneficial effects in several autoimmune diseases. The purpose of this study was to examine whether starting LDN was followed by changes in the dispensing of thyroid hormones to patients with hypothyroidism. Methods We performed a quasi-experimental before-after study based on the Norwegian Prescription Database. Study participants were identified by using reimbursement codes for hypothyroidism. Cumulative dispensed Defined Daily Doses and the number of users of triiodothyronine (T3) and levothyroxine (LT4) 1 year before and after the first LDN prescription was compared in three groups based on LDN exposure. Results We identified 898 patients that met the inclusion criteria. There was no association between starting LDN and the subsequent dispensing of thyroid hormones. If anything, there was a tendency towards increasing LT4 consumption with increasing LDN exposure. Conclusion The results of this study do not support claims of efficacy of LDN in hypothyroidism.

scholarly journals Durability of different types of Mouthwashes on the Salivary Buffering system in Orthodontic Patients.

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Israa R. Alkasso ◽  
Sarmad S. Salih Al Qassar ◽  
Ghada A. Taqa
Keyword(s):  
Green Tea ◽  
Tap Water ◽  
Placebo Control ◽  
Beneficial Effects ◽  
Salivary Ph ◽  
Before And After ◽  
Carbonated Beverage ◽  
Orthodontic Patients ◽  
Mouth Wash ◽  
Age Range

The fast elevation of the salivary pH in orthodontic patients has acritical role to safe the teeth and encourage the orthodontic treatment after acidic challenger. As their baseline salivary pH is dropped during fixed orthodontic treatments.Aims: this study was aimed to evaluate the durability of three types of mouthwashes on the salivary buffering capacity in orthodontic patients at 0, 5, 10, 15 mints after acidic challenger using direct pH meter.Material and method: 80 orthodontic patients; age range (13-21years) were distributed into four groups; 20/ each, the salivary pH were recorded using compact pH meter (LAQUAtwin, HORIBA's, Kyoto, Japan) before and after administration of carbonated beverage (100 mm coca cola) and directly after gargling with 100 ml of the tested mouthwashes (herbal, green tea and chlorohexidine mouthwash) beside tap water as placebo control. The pH was documented again at 0, 5, 10 and 15 mins after each mouthwash gargling. One way ANOVA analysis and Duncan multiple were used for salivary pH analysis, p≤0.05.Results: non-significant differences were found at 0, 5, 10, 15 mints in comparison with baseline pH after herbal mouthwash gargling, the same result was shown with chlorohexidine mouth wash but with less defined border. Salivary pH after green tea gargling showed clear oscillatory results after the same tested periods.Conclusions: Herbal mouthwash is the best type to improve salivary pH for longer duration after acidic challenger. While Chlorohexidine mouthwash shows beneficial effects in elevation salivary pH with less duration. Green tea mouthwash fail to control salivary pH for long duration. 

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

STUDY OF CXCL12, CCR4, EGFR GENE EXPRESSION IN MIGRATING MYELOMONOBLASTIC LEUKEMIA CELLS BEFORE AND AFTER CHEMOTHERAPY

2019 ◽  
Vol 1 (1) ◽  
pp. 100-104
Author(s):  
A. B. Filina ◽  
O. A. Svitich ◽  
Yu. I. Ammur ◽  
A. K. Golenkov ◽  
E. F. Klinushkina ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mononuclear Cells ◽  
Boyden Chamber ◽  
External Stimulation ◽  
Healthy Donors ◽  
Genes Expression ◽  
Before And After ◽  
Chemokine Cxcl12 ◽  
And Migration ◽  
Cell Chemotaxis

Аim. A study of CXCL12 effect on the migration of mononuclear cells isolated from healthy patients, from patients with myelomonoblastic leukemia before and after chemotherapy and the study of CCR4, EGFR and CXCL12 genes expression after exposure to CXCL12. Materials and methods. The chemotaxis of mononuclear cells (MNCs) of healthy donors and patients with myelomonoblastic leukemia was studied in a Boyden chamber, followed by isolation of RNA, reverse transcription and PCR-RV. Results. A significant increase in myelomonoblasic cell chemotaxis towards CXCL12 after chemotherapy was demonstrated, as well as a decrease in the expression of this chemokine in tumor cells before chemotherapy after exposure to CXCL12. Сonclusion. Presumably, the tumor cells themselves produce CXCL12 in large amounts, which is necessary for the disturbance of intercellular interactions and further intravasation, whose production may decrease with external stimulation by the same chemokine. CXCL12 also helps to increase the expression level of EGFR and CCR4, which leads to increased tumor proliferation and migration of tumor cells.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals Reduction in mobility and COVID-19 transmission

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Nouvellet ◽  
Sangeeta Bhatia ◽  
Anne Cori ◽  
Kylie E. C. Ainslie ◽  
Marc Baguelin ◽  
...  
Keyword(s):  
Predictive Ability ◽  
Control Measures ◽  
Social Distancing ◽  
Beneficial Effects ◽  
Mobility Data ◽  
Strict Control ◽  
Before And After ◽  
Proxy Measure ◽  
Lower Transmission ◽  
The Relationship

AbstractIn response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27–77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49–91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12–48%]) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.

scholarly journals Efficacy and Safety of Long-Term Low-Dose Clarithromycin in Patients With Refractory Chronic Sinusitis After Endoscopic Sinus Surgery: A Prospective Clinical Trial

2021 ◽  
pp. 014556132110320
Author(s):  
Han Chen ◽  
Bing Zhou ◽  
Qian Huang ◽  
Cheng Li ◽  
Yubin Wu ◽  
...  
Keyword(s):  
Oral Administration ◽  
Nasal Cavity ◽  
Endoscopic Sinus Surgery ◽  
Low Dose ◽  
Continuous Treatment ◽  
Sinus Surgery ◽  
Efficacy And Safety ◽  
Endoscopic Findings ◽  
Before And After

Objective: To observe the efficacy and safety of postoperative long-term low-dose oral administration of clarithromycin in patients with refractory chronic rhinosinusitis (RCRS), to explore the characteristics of postoperative microbiota in the nasal cavity in patients with RCRS, and to compare the differences and changes in microbiota in the nasal cavity before and after medication. Methods: This was a prospective, self-controlled study. Eighteen patients with RCRS who had persistent symptoms after endoscopic sinus surgery and standard therapy with normal immunoglobulin E and eosinophil level were included. Low dose (250 mg, once daily) clarithromycin was orally administrated for 12 weeks. Symptom severity and endoscopic findings were evaluated before, after 4 weeks, and 12 weeks of treatment, and nasal cavity microbiota was analyzed simultaneously. Results: A total of 18 patients with RCRS were enrolled and 17 patients completed the study. Four weeks after oral administration of clarithromycin, significant improvement was observed in subjective symptoms including nasal congestion, rhinorrhea, postnasal drip, and general discomfort, as well as endoscopic findings including general surgical cavity condition, rhinedema, and rhinorrhea ( P < .05). After continuous treatment to the 12th week, symptoms showed significant improvement compared with baseline, and endoscopic score showed significant improvement compared with both baseline and 4 weeks after treatment. Analysis of middle nasal meatus flora revealed a significant decrease of Streptococcus pneumoniae after 12 weeks of clarithromycin treatment ( P < .05), while the richness, composition, and diversity were similar before and after treatment. Patients enrolled experienced no adverse drug reaction or allergic reaction, nor clinical significant liver function impairment observed. Conclusion: Postoperative low-dose long-term oral administration of clarithromycin in patients with RCRS can improve the clinical symptoms and facilitate the mucosal epithelialization, with good tolerance and safety. The efficacy of clarithromycin in patients with RCRS may be related to its regulatory effect on nasal cavity microbiota.

scholarly journals Brain Training and Sulforaphane Intake Interventions Separately Improve Cognitive Performance in Healthy Older Adults, Whereas a Combination of These Interventions Does Not Have More Beneficial Effects: Evidence from a Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 352
Author(s):  
Rui Nouchi ◽  
Qingqiang Hu ◽  
Toshiki Saito ◽  
Natasha Yuriko dos Santos Kawata ◽  
Haruka Nouchi ◽  
...  
Keyword(s):  
Older Adults ◽  
Active Control ◽  
Processing Speed ◽  
Cognitive Functions ◽  
Controlled Trial ◽  
Memory Performance ◽  
Brain Training ◽  
Beneficial Effects ◽  
Before And After ◽  
Double Blinded

Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults. Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period. Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention’s beneficial effects on cognition. Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions.

scholarly journals The Influence of Tart Cherry (Prunus cerasus, cv Montmorency) Concentrate Supplementation for 3 Months on Cardiometabolic Risk Factors in Middle-Aged Adults: A Randomised, Placebo-Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1417
Author(s):  
Rachel Kimble ◽  
Karen M. Keane ◽  
John K. Lodge ◽  
Glyn Howatson
Keyword(s):  
Vascular Function ◽  
Controlled Trial ◽  
High Sensitivity ◽  
Metabolic Health ◽  
Cardiometabolic Health ◽  
Middle Aged ◽  
Concentrate Supplementation ◽  
Health Indices ◽  
Before And After ◽  
Middle Aged Adults

Background: Tart Montmorency cherries (MC) have been shown to be rich in anthocyanins and other phytochemicals known to have anti-inflammatory properties and influence pathways that might improve cardiometabolic health. However, there is limited evidence for the longer-term use of tart cherries on these indices. The aim of the current study was to investigate the influence of MC concentrate on cardiometabolic health indices following a 3-month supplementation period. Methods: Fifty middle-aged adults (34 males and 16 females; mean ± SD age: 48 ± 6 years and BMI: 27.6 ± 3.7 kg/m2) completed a randomised, placebo-controlled parallel study in which they either received MC or an isocaloric placebo. Participants drank 30 mL of their allocated treatment twice per day for 3 months. Vascular function (blood pressure [BP], heart rate [HR], pulse wave velocity and analysis [PWV/A], and flow mediated dilation [FMD]) as well as indices of metabolic health (insulin, glucose, lipid profiles, and high sensitivity C reactive protein) were measured following an overnight fast before and after the 3 months. Results: No effect of the intervention between the groups was observed for vascular function or metabolic health variables following the intervention (p > 0.05). However, MC concentrate was shown to be safe and well-tolerated and, importantly, did not have any deleterious effects on these outcomes. In conclusion, MC has no influence on cardiometabolic indices in middle-aged adults.

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