Optic Nerve Neuroprotection in Glaucoma: A Narrative Review.

In recent years, researchers have been interested in neuroprotective therapies as a cutting-edge therapeutic strategy to treat neurodegenerative disorders by shielding the brain system from harmful events. Millions of individuals worldwide suffer from glaucoma, an ocular neurodegenerative disease characterized by gradual excavation of the optic nerve head, retinal axonal damage, and consequent visual loss. The pathology's molecular cause is still mostly unknown, and the current treatments are not able to alter the disease's natural progression. Thus, the modern approach to treating glaucoma consists of prescribing medications with neuroprotective properties, in line with the treatment strategy suggested for other neurodegenerative diseases. For this reason, several naturally derived compounds, including nicotinamide and citicoline, have been studied throughout time to try to improve glaucoma management by exploiting their neuroprotective properties. The purpose of this review is to examine the naturally derived compounds that are currently utilized in clinical practice for neuroprotection in glaucomatous patients based on scientific data, emphasizing these compounds' pivotal mechanism of action as well as their proven therapeutic and neuroprotective benefits.

The Use of Nigella sativa in Cardiometabolic Diseases.

Nigella sativa L. is an herb that is commonly used in cooking and in traditional medicine, particularly in Arab countries, the Indian subcontinent, and some areas of eastern Europe. Nigella sativa is also called "black cumin" or "black seeds", as the seeds are the most-used part of the plant. They contain the main bioactive component thymoquinone (TQ), which is responsible for the pleiotropic pharmacological properties of the seeds, including anti-oxidant, anti-inflammatory, anti-hypertensive, anti-hepatotoxic, hypoglycemic, and lipid-lowering properties. In this narrative review, both the potential mechanisms of action of Nigella sativa and the fundamental role played by pharmaceutical technology in optimizing preparations based on this herb in terms of yield, quality, and effectiveness have been outlined. Moreover, an analysis of the market of products containing Nigella sativa was carried out based on the current literature with an international perspective, along with a specific focus on Italy.

ORal anticoaGulants in diAbetic and Nondiabetic patients with nOn-valvular atrial fibrillatioN (ORGANON).

BACKGROUND: Diabetes represents a pro-thrombotic condition. OBJECTIVES: The primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. METHODS: We enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. RESULTS: We did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. CONCLUSION: DOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.

Recruitment and retention of diverse couples in relationship education with integrated economic services.

Compared to higher income couples, those with low incomes experience a host of challenges and disparities in their intimate relationships, including lower levels of relationship satisfaction, higher rates of breakup of cohabiting relationships, and higher rates of divorce. In recognition of these disparities, a number of interventions targeting couples with low incomes have been developed. These interventions historically focused primarily on improving relationship skills through relationship education, but in recent years a new approach that integrates economic-focused interventions alongside relationship education has emerged. This integrated approach is intended to better address the challenges facing couples with low incomes, but the theory-driven, top-down approach to intervention development leaves open the question of whether couples with low incomes are interested in participating in a program that combines these two disparate components. The current study draws from a large randomized controlled trial of one such program (N = 879 couples) to provide descriptive information about the recruitment and retention of couples with low incomes in a study of relationship education with integrated economic services. Results indicate that it is possible to recruit a large, linguistically, and racially diverse sample of couples living with low income to participate in an integrated intervention, but the uptake of relationship-focused services was higher than the uptake of economic-focused services. Additionally, attrition over a 1-year follow-up data collection period was low but required labor-intensive efforts to reach participants for the survey. We highlight successful strategies for the recruitment and retention of diverse couples and discuss implications for future intervention efforts.

The role of selected nutraceuticals in management of prediabetes and diabetes: An updated review of the literature.

Dysglycemia is a disease state preceding the onset of diabetes and includes impaired fasting glycemia and impaired glucose tolerance. This review aimed to collect and analyze the literature reporting the results of clinical trials evaluating the effects of selected nutraceuticals on glycemia in humans. The results of the analyzed trials, generally, showed the positive effects of the nutraceuticals studied alone or in association with other supplements on fasting plasma glucose and post-prandial plasma glucose as primary outcomes, and their efficacy in improving insulin resistance as a secondary outcome. Some evidences, obtained from clinical trials, suggest a role for some nutraceuticals, and in particular Berberis, Banaba, Curcumin, and Guar gum, in the management of prediabetes and diabetes. However, contradictory results were found on the hypoglycemic effects of Morus, Ilex paraguariensis, Omega-3, Allium cepa, and Trigonella faenum graecum, whereby rigorous long-term clinical trials are needed to confirm these data. More studies are also needed for Eugenia jambolana, as well as for Ascophyllum nodosum and Fucus vesiculosus which glucose-lowering effects were observed when administered in combination, but not alone. Further trials are also needed for quercetin.

Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial.

Aim: To evaluate if VSL#3® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08)] therapy could improve hepatic parameters. Methods: We enrolled 60 Caucasian patients aged ≥ 18 years of either sex with the diagnosis of non-alcoholic fatty liver disease (NAFLD), according to practice guidance, in a double-blind, placebo-controlled study. Patients were randomized to take placebo or VSL#3®, 2 sachets/day in the morning for 3 months. VSL#3® and placebo were self-administered. Results: We did not observe any change in body mass index (BMI), circumferences, fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and adiponectin (ADN) with neither treatment. A statistically significant triglycerides (Tg) decrease (p < 0.05 vs. baseline, and p < 0.05 vs. placebo, respectively) and high-sensitivity C-reactive protein (Hs-CRP) decrease (p < 0.05 vs. baseline) was observed in the group of patients being treated with VSL#3® compared with placebo. Transaminases and gamma-glutamyltransferase (γ-GT) were significantly reduced in VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and hepatic steatosis index (HSI) were significantly lower than the VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. All patients reported an improvement or the disappearance of hepatic steatosis. Conclusion: Probiotic therapy with VSL#3® ameliorates hepatic parameters and echography grading, while reducing Tg and the inflammatory status, without any difference between men and women.

Evaluation of the Effect on Sexual Performance of a Nutraceutical Combination Containing Alpha Lipoic Acid, Vitis vinifera L. and Ginkgo biloba, Compared to Placebo, Avanafil or a Combination of Nutraceutical Plus Avanafil in Males With Type 2 Diabetes Mellitus With Erectile Dysfunction.

Aim: To evaluate if therapy with a nutraceutical combination of alpha lipoic acid, Vitis vinifera L. and Ginkgo biloba (Blunorm forte®) can be helpful and be synergic with Avanafil. Methods: The trial included 123 males with type 2 diabetic mellitus and with erectile dysfunction (ED), aged ≥18 years. Patients were divided in four different arms: 1st arm: placebo during the three months of treatment and before sexual act; 2nd arm: placebo for three months and Avanafil: 1 tablet, 200 mg, 15-30 minutes before sexual act; 3rd arm: Blunorm forte: 1 tablet, 40 minutes before the meal (breakfast) during the three months and Avanafil: 1 tablet, 200 mg, 15-30 minutes before sexual act; 4th arm: Blunorm forte: 1 tablet, 40 minutes before the meal (breakfast and dinner) during the three months and placebo 15-30 minutes before sexual act. Results: A significant reduction of fasting plasma glucose, and homeostasis model assessment-insulin resistance index were recorded both in Avanafil + Blunorm forte and with Blunorm forte. Metalloproteinases-2, and -9 were reduced in the Avanafil + Blunorm forte group. High sensitivity-C-reactive protein was decreased by both Avanafil, and Avanafil + Blunorm forte group. No variations were recorded with the other treatments. The group treated with Blunorm forte and Avanafil reached a higher International Index of Erectile Function (IIEF) score after 3 months of therapy compared to baseline and placebo and compared to Avanafil and Blunorm forte taken alone. Conclusion: Blunorm forte® can be helpful and synergic with Avanafil in increasing sexual performance compared to placebo.

Lipoprotein(a) Serum Levels Predict Pulse Wave Velocity in Subjects in Primary Prevention for Cardiovascular Disease with Large Apo(a) Isoforms: Data from the Brisighella Heart Study.

In the last decades, high serum levels of lipoprotein(a) (Lp(a)) have been associated with increased cardiovascular disease (CVD) risk, in particular among individuals with smaller apolipoprotein(a) (apo(a)) isoforms than those with larger sizes. The aim of our analysis was to evaluate whether Lp(a) levels could predict early vascular aging, and whether smaller apo(a) isoforms had a predictive value for vascular aging different than larger apo(a) isoforms in a cohort of subjects free from CVD. We considered the data of a subset of Brisighella Heart Study (BHS) participants free from CVD (462 men and 516 women) who were clinically evaluated during the 2012 BHS population survey. Predictors of arterial stiffness, measured as carotid-femoral pulse wave velocity (cfPWV) were estimated by the application of a step-wise linear regression model. In our cohort, there were 511 subjects with small apo(a) size and 467 subjects with large apo(a) isoforms. Subjects with larger apo(a) isoform sizes had significantly lower serum levels of Lp(a). In the BHS subpopulation sample, cfPWV was predicted by age, systolic blood pressure (SBP), serum levels of high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and sex, higher HDL-C serum levels and female sex associated with lower values of cfPWV. In subjects with smaller apo(a) isoform sizes, predictors of cfPWV were age, SBP, sex and serum levels of HDL-C, being higher HDL-C serum levels and female sex associated to lower values of cfPWV. In subjects with larger apo(a) isoform sizes, cfPWV was predicted by age, SBP, serum levels of Lp(a) and sex, with female sex associated with lower values of cfPWV. In our subpopulation sample, Lp(a) did not predict cfPWV. However, in subjects with large apo(a) isoform sizes, Lp(a) was a significant predictor of arterial stiffness.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial.

Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Proprotein convertase subtilisin/kexin type 9 inhibitors treatment in dyslipidemic patients: a real world prescription.

AIM: Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab. RESULTS: Total cholesterol significantly decreased progressively until the fourth year; after 4 years there was a significant reduction (-125.5 mg/dl, -51.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -2.8 mg/dl (-2.3%) compared with the third year. Low-density lipoprotein-cholesterol (LDL-C) also decreased significantly until the fourth year. After 3 years, there was a significant reduction (-117.8 mg/dl, -71.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year) and -13.9 mg/dl (-22.8%) compared with the second year; after 4 years there was a significant reduction (-121.4 mg/dl, -73.7%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -3.6 mg/dl (-7.7%) compared with the third year. High-density lipoprotein-cholesterol increased significantly only during the fourth year of detection. After 3 years, there was a nonsignificant increase (4.9 mg/dl, 10.0%, P = 0.061 vs baseline) and 1.6 mg/dl (3.1%) compared with the second year; after 4 years, there was a significant increase (5.2 mg/dl, 10.6%, P < 0.05 vs baseline) and 0.3 mg/dl (0.6%) compared with the third year. The value of Tg was significantly reduced progressively until the second year and then stabilized in the third and fourth years. After 3 years, the value of Tg stabilized (-48.6 mg/dl, -32.4%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) and -4.8 mg/dl (-4.5%) compared with the second year; after 4 years (-46.4 mg/dl, -31.0%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) there was a slight and nonsignificant increase of 2.2 mg/dl (2.2%) compared with the third year. Regarding adverse events, both drugs were well tolerated. CONCLUSIONS: We showed that PCSK9 inhibitors are well tolerated and provide long-term significant LDL-C lowering in individuals with hyperlipidemia.

Detection of sieric BAG3 in patients affected by cardiovascular diseases: State of art and perspectives.

BAG3 is highly expressed in the heart and its functions are essential in maintaining cardiac muscle cells homeostasis. In the past, BAG3 was detected in serum from advanced heart failure patients and its higher levels were correlated to an increased death risk. Moreover, it has also been reported that BAG3 levels in serum are increased in patients with hypertension, a known cardiovascular risk marker. Evidence from different laboratories suggested the possibility to use BAG3-based strategies to improve the clinical outcome of cardiovascular disease patients. This review aims to highlight the biological roles of intracellular or secreted BAG3 in myocardiocytes and propose additional new data on the levels of sieric BAG3 in patients with acute myocardial infarction (AMI), never assessed before. We evaluated BAG3 serum levels in relation to cardiovascular risk parameters in 64 AMI patients aged ≥18 years of either sex. We observed significant (p < .01) correlations of BAG3 positivity with dyslipidemic status and diabetic disease. We did not observe any significant correlations of BAG3 levels with smoking habit, hypertension or familiarity for AMI, although BAG3-positive seemed to be more numerous than BAG3-negative patients among hypertensives and among patients with familiarity for AMI. Furthermore, a significant (p < .001) correlation of BAG3 positivity with diuretics assumption was also noted. In conclusion, 32.8% of the patients were BAG3-positive and were characterized by some particular features as comorbidity presence or concomitant therapies. The significance of these observations needs to be verified by more extensive studies and could help in the validation of the use of BAG3 as a biomarker in heart attack risk stratification.

Effects of experimental colitis in rats on incretin levels, inflammatory markers, and enteric neuronal function.

INTRODUCTION: The aim of the study was to assess the effects of chronic inflammation on incretin levels, inflammatory markers, and enteric neuronal function measured in isolated preparations of smooth muscle of rat. MATERIAL AND METHODS: We induced experimental colitis using 2,4-dinitrobenzenesulfonic acid (DNBS) in 17 Albino male Sprague-Dawley rats, while 16 rats were used as a control. They were housed in temperature-controlled rooms in a 12-h light/dark cycle at 22-24°C and 50 to 60% humidity. We evaluated in both inflamed and healthy rats: fasting plasma glucose concentration, fasting plasma insulin, myeloperoxidase, active glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and GLP-2 levels, adiponectin, and C-reactive protein (CRP). We also evaluated colonic longitudinal smooth muscle contractile activity. RESULTS: Intrarectal administration of DNBS reduced body weight gain in inflamed rats. We recorded higher levels of fasting plasma glucose, and insulin in inflamed rats. We observed higher levels of myeloperoxidase and CRP, and lower levels of ADN in inflamed rats. We recorded higher levels of GIP, GLP-1, and GLP-2 in inflamed rats compared to the healthy ones. Regarding functional response of colon intestinal smooth muscle after electrical stimulation, we recorded a lower functional response of colon intestinal smooth muscle after electrical stimulation in inflamed rats. CONCLUSIONS: We can conclude that chronic inflammation leads to an increase of incretin levels and to a decrease of functional response of colon intestinal smooth muscle after electrical stimulation.

Metabolic Actions of a Supplement of Ilex Paraguariensis (An Extract of the Leaf Standardized to 2% I-Deoxinojirimcina), White Mulberry and Chromium Picolinate in Nondiabetic Subects with Dysglycemia: A Randomized Trial.

AIM: To prove if a nutraceutical containing Ilex paraguariensis (Ilex L. spp. Aquifoliales) (an extract of the leaf standardized to 2% I-deoxinojirimcina), white mulberry (Morus spp., Moraceae), and chromium picolinate can be effective in improving glycemic status in subject with dysglycemia. METHODS: We randomized patients to consume placebo or the nutraceutical, self-administered once a day, one tablet at breakfast, for 3 months. RESULTS: A reduction in fasting plasma glucose, postprandial glucose, and glycated hemoglobin was observed with the nutraceutical combination, both compared to baseline and placebo. Data suggested a decrease in the Homeostasis Model Assessment index with the nutraceutical, both compared to baseline and placebo. The M value, an index of insulin sensitivity, obtained after nutraceutical treatment was higher compared to baseline. We recorded a decrease in total cholesterol, low-density lipoprotein-cholesterol, and triglycerides with the nutraceutical combination compared to baseline and placebo. A decrease in high-sensitivity C-reactive protein was observed with the nutraceutical combination compared to baseline and placebo. CONCLUSIONS: A nutraceutical containing Ilex paraguariensis, white mulberry, and chromium picolinate can be helpful in improving glycemic status and lipid profile in dysglycemic subjects.

Nutraceutical Approach to Preventing Coronavirus Disease 2019 and Related Complications.

Introduction: Several months ago, Chinese authorities identified an atypical pneumonia in Wuhan city, province of Hubei (China) caused by a novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19". Evidence Acquisition: Several approaches are currently underway for the treatment of this disease, but a specific cure remains to be established. Evidence Synthesis: This review will describe how the use of selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients. Conclusions: Even if a specific and effective cure for COVID-19 still has some way to go, selected nutraceuticals could be helpful, in addition to pharmacological therapy, in preventing some COVID-19-related complications in infected patients.

Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers.

Aims: Psoriasis is an immune-mediated dermatosis with cardio-metabolic comorbidities. The aim of this study was to assess insulin-resistance, lipid abnormalities, and cardiovascular risk biomarkers in psoriatic patients with or without type 2 diabetes mellitus (T2DM). Methods and materials: We enrolled 425 patients: 86 psoriatics, 69 psoriatics with T2DM, 120 T2DM patients, and 150 healthy subjects. We measured the Psoriasis Area and Severity Index (PASI), body mass index (BMI), insulin-resistance parameters [glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), fasting plasma insulin (FPI), and with homeostasis model assessment index (HOMA index)], lipidic panel, plasminogen activator inhibitor-1 (PAI-1), homocysteine, soluble adhesion molecules, matrix metalloproteinase, and adipocytokines. Results: FPG, HbA1c, and HOMA-IR were higher in diabetics with psoriasis (p < 0.0001) than in psoriatics. FPI levels were higher in diabetics with psoriasis than in diabetics and psoriatics (p < 0.0001), and higher in psoriatics than controls (p < 0.0001). Psoriatics and diabetics with psoriasis showed higher triglyceride and LDL-C levels (p < 0.0001) than diabetics. Homocysteine was higher in psoriatics and diabetics with psoriasis (p < 0.0001) than in diabetics. PAI-1 was higher in diabetics with psoriasis than diabetics (p < 0.01). sICAM-1 and sVCAM-1 were higher in diabetics with psoriasis than diabetics (p < 0.001 and p < 0.01) and psoriatics (p < 0.001 and p < 0.0001). Visfatin and resistin were lower in psoriatics (p < 0.0001) and in diabetics with psoriasis (p < 0.001 and p < 0.0001, respectively) than diabetics. Conclusions: A limitation of this study is that there is a significant difference in mean age between controls and other study groups: the lack of matching between case and control groups may interfere with the external validity of the study findings. Despite this, the study highlights a pathogenetic link between psoriasis, considered a pre-diabetic condition, and diabetes. Insulin-resistance seems to be the keystone of psoriasis comorbidities. Psoriasis reinforces diabetes, causing a greater cardiometabolic risk.

Effects of Oral Administration of Alprazolam and Lorazepam as Hypnotics on Cardiovascular Parameters in Hypertensive Patients.

BACKGROUND: Previous studies have suggested that evening intake of benzodiazepine affects blood pressure (BP) and/or heart rate (HR) in healthy and hypertensive subjects. The aim of this study was to compare the effect of chronic oral administration of alprazolam and lorazepam as hypnotics on ambulatory BP and HR in patients with mild hypertension. METHODS: Consecutive outpatients of both sexes with newly diagnosed, never-treated mild hypertension were randomized, after a 4-week placebo run-in period, to receive alprazolam 0.5 mg plus placebo, lorazepam 1 mg plus placebo, or placebo plus placebo for 2 weeks in 3 crossover periods, each separated by a 1-week placebo wash-out period. At the end of the initial placebo run-in and of each treatment period, 24-hour ambulatory BP and HR monitoring was performed using a noninvasive device. RESULTS: In the 32 patients, no treatment had any effect on 24-hour and daytime systolic BP (SBP), diastolic BP (DBP), and HR, which remained unchanged. During the nighttime, SBP and DBP values were unaffected by alprazolam, as compared with placebo, whereas DBP was significantly higher after treatment with lorazepam (+3.7%, P < 0.05 vs placebo). Nocturnal HR mean values were significantly increased by lorazepam (+10.1%, P < 0.01 vs placebo), whereas they did not change after alprazolam. CONCLUSIONS: In patients with mild hypertension, oral intake of alprazolam or lorazepam as hypnotics did not affect ambulatory BP or HR values. A slight increase in nighttime DBP was observed with lorazepam, whereas alprazolam showed no effect on nocturnal BP and HR, probably reflecting a stimulating effect of the drug on central α2-receptors.

A role for quercetin in coronavirus disease 2019 (COVID-19).

Several months ago, an outbreak of pneumonia of unknown aetiology was detected in Wuhan City (China) and the aetiological agent of the atypical pneumonia was isolated by the Chinese authorities as novel coronavirus (2019-nCoV or SARS-CoV-2). The WHO announced this new disease was to be known as "COVID-19." When looking for new antiviral compounds, knowledge of the main viral proteins is fundamental. The major druggable targets of SARS-CoV-2 include 3-chymotrypsin-like protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase, and spike (S) protein. Quercetin inhibits 3CLpro and PLpro with a docking binding energy corresponding to -6.25 and -4.62 kcal/mol, respectively. Quercetin has a theoretical, but significant, capability to interfere with SARS-CoV-2 replication, with the results showing this to be the fifth best compound out of 18 candidates. On the basis of the clinical COVID-19 manifestations, the multifaceted aspect of quercetin as both antiinflammatory and thrombin-inhibitory actions, should be taken into consideration.

Safety and Efficacy of Alpha Lipoic Acid During 4 Years of Observation: A Retrospective, Clinical Trial in Healthy Subjects in Primary Prevention.

AIM: To evaluate the safety of four different dosages of alpha lipoic acid (400, 600, 800, and 1200 mg) as food supplement on adverse events related to alpha lipoic acid consumption and efficacy on glycemic status and lipid profile in subjects with euglycemia or dysglycemia. METHODS: We conducted a retrospective, observational study enrolling 322 patients, 83 taking 400 mg/day, 78 taking 600 mg/day, 80 taking 800 mg/day, and 81 taking 1200 mg/day alpha lipoic acid, respectively. RESULTS: In the groups treated with alpha lipoic acid 800 and 1200 mg/day, we registered a reduction of FPG, TC, LDL-C, and Tg compared to baseline (p < 0.05 for all with alpha lipoic acid 800 mg/day, and p < 0.01 for all with alpha lipoic acid 1200 mg/day). The values recorded in the group treated with alpha lipoic acid 1200 mg/day were significantly lower compared to the ones obtained with alpha lipoic acid 400 mg/day. Moreover, alpha lipoic acid 1200 mg/day reduced Hs-CRP levels compared to baseline and compared to 400 mg/day (p < 0.05 for both). In the group treated with alpha lipoic acid at 800 mg/day, 5 subjects with IFG and 1 subject with IGT returned euglycemic. In the group treated with alpha lipoic acid at 1200 mg/day, 11 subjects with IFG and 3 subjects with IGT returned euglycemic. Adverse events of patients during alpha lipoic acid treatment included nausea, vomiting, dizziness, cutaneous rash, hypoglycemia, and hypotension. Adverse events did not differ among the four groups. CONCLUSION: The chronic use (4 years) of a food supplement containing alpha lipoic acid is well tolerated, without significant differences between lower and higher dosages and improves glycemic status and lipid profile but only if administered at high dosage.

Abscisic Acid Treatment in Patients with Prediabetes.

AIM: to evaluate the effects of abscisic acid (ABA), contained in dwarf peaches, on the regression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) conditions. MATERIALS AND METHODS: sixty-five patients with IFG or IGT were randomized to take ABA or placebo for 3 months. We evaluated: fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbA1c), fasting plasma insulin (FPI), homeostatic model assessment of insulin resistance (HOMA-IR), lipid profile and high sensitivity C-reactive protein (Hs-CRP). At baseline, and after 3 months, all patients underwent an oral glucose tolerance test (OGTT), an euglycemic hyperinsulinemic clamp, and a glucagon test. RESULTS: a significant reduction of HbA1c, FPG, PPG, FPI and HOMA-IR was observed in the ABA group. After 3 months, 26.7% of patients returned to a normal glycemic status in the ABA group versus zero patients in placebo group; 20.0% were classified as IFG and 53.3% as IGT in the nutraceutical group versus 33.3% and 63.3% in the placebo group. The M value was higher in the ABA group at the end of the treatment. Finally, Hs-CRP was reduced after 3 months of ABA consumption. CONCLUSIONS: abscisic acid can be effective in ameliorating glyco-metabolic compensation and in reducing inflammatory status in patients with IFG or IGT.

Lipid-lowering nutraceuticals update on scientific evidence.

: Cardiovascular diseases (CVDs) are the main cause of mortality worldwide. Risk factors of CVD can be classified into modifiable (smoking, hypertension, diabetes, hypercholesterolemia) through lifestyle changes or taking drug therapy and not modifiable (age, ethnicity, sex and family history). Elevated total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels have a lead role in the development of coronary heart disease (CHD), while high levels of high-density lipoprotein-cholesterol (HDL-C) seem to have a protective role.The current treatment for dyslipidemia consists of lifestyle modification or drug therapy even if not pharmacological treatment should be always considered in addition to lipid-lowering medications.The use of lipid-lowering nutraceuticals alone or in association with drug therapy may be considered when the atherogenic cholesterol goal was not achieved.These substances can be classified according to their mechanisms of action into natural inhibitors of intestinal cholesterol absorption, inhibitors of hepatic cholesterol synthesis and enhancers of the excretion of LDL-C. Nevertheless, many of them are characterized by mixed or unclear mechanisms of action.The use of these nutraceuticals is suggested in individuals with borderline lipid profile levels or with drug intolerance, but cannot replace standard lipid-lowering treatment in patients at high, or very high CVD risk.Nutraceuticals can also have vascular effects, including improvement in endothelial dysfunction and arterial stiffness, as well as antioxidative properties. Moreover, epidemiological and clinical studies reported that in patients intolerant of statins, many nutraceuticals with demonstrated hypolipidemic effect are well tolerated.