Phytonutrients of Bitter Apricot Seeds Modulate Human Lipid Profile and LDL Subfractions in Adults with Elevated Cholesterol Levels

The objective of the present study was to evaluate the effect of short-term consumption of bitter apricot seeds phytonutrients on cardiovascular risk factors with a special focus on LDL cholesterol subfractions using the Lipoprint system. A group of 34 adult volunteers (21 female/13 male) consumed 60 mg kg−1 of body weight of bitter apricot seeds daily for 42 days. Subjects were divided into two groups: one with normal cholesterol levels (NTC) and one with elevated total cholesterol levels (ETC). Blood serum levels of total cholesterol (T-C), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), and triglycerides (TG) did not change significantly (p > 0.05) in NTC group. However, there were significant decreasing of T-C (p ˂ 0.05) and LDL-C (p < 0.01) in ETC group. The LDL1, LDL2, and atherogenic LDL3−7 subfractions progressively decreased after 42 days of apricot seeds consumption in ETC group (p < 0.05). Apricot seeds consumption was associated with a significant increase in the mean LDL particle size especially in ETC group (p ˂ 0.01). The results of the present study support the hypothesis that daily consumption of bitter apricot seeds for 42 days positively modified the lipoprotein profile in the group with elevated total cholesterol.

Factors Associated with Nutritional Deficiency Biomarkers in Candidates for Bariatric Surgery: A Cross-Sectional Study in a Peruvian High-Resolution Clinic

Previous studies have described multiple nutritional deficiencies after bariatric surgery (BS). However, few studies have evaluated these deficiencies prior to BS, specifically in Latin America. This study aimed to determine the factors associated with nutritional deficiency biomarkers in candidates for BS in Peru. We included adults of both sexes, aged 18 to 59 years, admitted to a Peruvian clinic with a body mass index (BMI) ≥ 30 kg/m2; they were candidates for BS from 2017 to 2020. We considered the serum levels of hemoglobin and albumin (in tertiles) as the nutritional deficiency biomarkers. In order to assess the associated factors, we calculated crude (cPR) and adjusted prevalence ratios (aPR) with their respective 95% confidence intervals (95%CI). We analyzed 255 patients: 63.1% were males, with a mean age of 37.1 ± 10.3 years and mean hemoglobin and albumin values of 14.0 ± 1.5 g/dL and 4.6 ± 0.4 g/dL, respectively. We found that males (aPR = 1.86; 95%CI: 1.26–2.73; p = 0.002), participants between 30 and 49 (aPR = 2.02; 95%CI: 1.24–3.28; p = 0.004) or 50 years or more (aPR = 2.42; 95%CI: 1.35–4.35; p = 0.003), participants with a BMI ≥40 kg/m2 (aPR = 1.68; 95%CI: 1.09–2.60; p = 0.018), participants with impaired high-density lipoprotein levels (aPR = 1.43; 95%CI: 1.01–2.05; p = 0.049) and individuals in the high tertile of C-reactive protein (aPR = 6.94; 95%CI: 3.37–14.32; p < 0.003) had a higher probability of being in the lower tertile of albumin. In addition, we found that the male sex (aPR = 6.94; 95%CI: 3.37–14.32; p < 0.001) and elevated cholesterol levels (aPR = 0.71; 95%CI: 0.52–0.97; p = 0.034) were associated with the lowest hemoglobin tertile. In our setting, nutritional deficiency biomarkers were associated with sociodemographic, anthropometric and laboratory markers. The pre-bariatric surgery correction of nutritional deficiencies is essential, and can prevent major complications after surgery.

Discovery of a Positive Allosteric Modulator of Cholecystokinin Action at CCK1R in Normal and Elevated Cholesterol

Drugs useful in prevention/treatment of obesity could improve health. Cholecystokinin (CCK) is a key regulator of appetite, working through the type 1 CCK receptor (CCK1R); however, full agonists have not stimulated more weight loss than dieting. We proposed an alternate strategy to target this receptor, while reducing likelihood of side effects and/or toxicity. Positive allosteric modulators (PAMs) with minimal intrinsic agonist activity would enhance CCK action, while maintaining spatial and temporal characteristics of physiologic signaling. This could correct abnormal stimulus–activity coupling observed in a high-cholesterol environment observed in obesity. We utilized high-throughput screening to identify a molecule with this pharmacological profile and studied its basis of action. Compound 1 was a weak partial agonist, with PAM activity to enhance CCK action at CCK1R, but not CCK2R, maintained in both normal and high cholesterol. Compound 1 (10 µM) did not exhibit agonist activity or stimulate internalization of CCK1R. It enhanced CCK activity by slowing the off-rate of bound hormone, increasing its binding affinity. Computational docking of Compound 1 to CCK1R yielded plausible poses. A radioiodinatable photolabile analogue retained Compound 1 pharmacology and covalently labeled CCK1R Thr211, consistent with one proposed pose. Our study identifies a novel, selective, CCK1R PAM that binds to the receptor to enhance action of CCK-8 and CCK-58 in both normal and disease-mimicking high-cholesterol environments. This facilitates the development of compounds that target the physiologic spatial and temporal engagement of CCK1R by CCK that underpins its critical role in metabolic regulation.

Effect of Triphala Kajjali tablet - an Ayurvedic herbomineral formulation for the management of metabolic syndrome: a single case study

Metabolic syndrome (MS) is a group of disorders that includes abdominal obesity, diabetes, hypertension, and elevated cholesterol. Approximately 25% of the adult populations are affected by MS. Gradually this number is increasing because of poor lifestyles, faulty dietary pattern, physical inactivity, stressful life and rapid urbanization. A 50-year-old female patient visited to OPD of Kayachikitsa department ITRA, Jamnagar, with the complaints of gradual weight gain with excess body fat around the abdomen and waist region, numbness and burning sensation at bilateral feet, and breathlessness on exertion. After investigation, she was diagnosed as a case of MS as per National Cholesterol Education Program (NCEP), adult treatment panel III (revised in 2005) guideline. She was treated with Triphala Kajjali tablet for 12 weeks along with lifestyle modification. After completion of treatment, investigations revealed reduction in fasting blood sugar from 113 mg/dL to 80 mg/dL, serum cholesterol level was decreased to 148 mg/dl from 216 mg/dl, serum triglycerides level was reduced to 150 mg/dL from 187 mg/dL and serum LDL was reduced to 68.3 mg/dl from 118.7 mg/dl. Her weight reduced to75 kg from 85 kg, and waist circumference reduced to 92 cm from 100cm, and blood pressures also reduced up to 122/82 mmHg from 140/90 mmHg. Hence, it can be concluded that Triphala Kajjali tablet along with lifestyle modification are effective in the management of MS, as it possesses Kapha Medohara properties.

Real-Life Use of Nilotinib for Chronic Phase CML Demonstrates Similar Efficacy and Rate of Cardiovascular Events As Enestnd

Introduction: Nilotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) widely used for the treatment of Philadelphia chromosome positive chronic myeloid leukemia (CML). ENESTnd, which compared two doses of nilotinib to imatinib for patients with newly diagnosed CML, demonstrated superior rates of major molecular responses (MMRs) at 12 months in patients treated with nilotinib. However, a relative increase in cardiovascular events (CVE) was observed, including ischemic heart disease, stroke, and/or peripheral artery disease among nilotinib-treated patients. Notably, at a median 5-year follow up, 7.5% of patients on nilotinib 300mg twice daily experienced a CVE (Hochaus, Leukemia, 2016) and by 10-years of follow up, approximately 20% of patients treated with nilotinib developed a CVE (Kantarjian, Leukemia, 2021). The baseline Framingham general cardiovascular risk scores and total dose exposure were predictive of patients' risk of developing CVE. In the province of Quebec, Canada, the GQR LMC-NMP (Groupe Québécois de recherche en leucémie myéloide chronique et néoplasie myéloproliférative) has maintained a registry of nearly all patients with CML since 2011. Using this 900+-patient registry, we examined molecular responses and the rate of CVE among patients receiving nilotinib as frontline therapy for CML, to determine if they were similar to those observed in ENESTnd. Methods: We identified all patients with chronic phase CML in the registry who were initiated on nilotinib for chronic phase CML. Baseline patient characteristics included were age, sex, Sokal index, baseline comorbidities, molecular response, cardiovascular complications, duration of exposure to nilotinib, dose adjustment, dose discontinuation and CVE on therapy. Results: In total, 94 patients received nilotinib as frontline treatment starting in 2008 (Table 1). The median age of the population was 58 years, 50.5% were male. The most common cardiovascular comorbidity prior to nilotinib treatment was hypertension (23.4%) followed by elevated cholesterol (21.3%), and prior CVE (12%). Seventeen patients had a low Sokal index, 26 intermediate and 24 high, 25 missing. Sixty-five patients received nilotinib at a total of 600 mg per day, 29 patients had a dose reduction at some point in their treatment and 18 patients were on either 300 or 400 mg daily. The median follow-up time was 67.0 months (range 0.5 to 159), and median nilotinib exposure time was 38.5 months (range 0.5 to 144). Forty-six patients (48.9%) discontinued nilotinib, 6 for a treatment free remission (TFR). While on nilotinib, 63 patients achieved MMR (72.4%) and 43 achieved MR 4.5 (49.6%) by 5 years of treatment, with 52 (55.3%) and 22 (23.4%) patients achieving MMR or MMR4.5 within a year, respectively. There was a total of 7 CVE in 6 patients: six myocardial infarctions and one ischemic stroke (Table 2). No patients developed peripheral artery disease. The mean time of exposure to nilotinib in these 6 patients was 28.6 months. Two patients had a high Sokal index, 3 intermediate and 1 low. One patient received dose-reduced nilotinib. These patients were co-morbid with diabetes (3), hypertension (3), elevated cholesterol (1) and one had a myocardial infarct prior to starting nilotinib, two patients did not have any risk factors. Only one of these patients has remained on nilotinib. All patients with a CVE were alive at the time of this report. Conclusion: We present real world data on the efficacy and safety of nilotinib in the frontline treatment of CML. Our data indicate that molecular responses and toxicities are similar to the ENESTnd trial. Of the 94 treated patients, the rate of MMR and CVE were 72% and 7.4% at 5.5 years of follow up, respectively, which is similar to that observed in ENESTnd, where 77% of patients experienced MMR and 7.5% CVE at this timepoint (Hochaus, Leukemia, 2016). All but one patient with a CVE in our study continued nilotinib, suggesting a reluctance among physicians to continue in the face of CVE. While there were 11 patients with prior CVE, only one of these developed a CVE on nilotinib. Current GQR-LMC CML management guidelines recommend estimation of Framingham score and management of cardiovascular risk factors for all patients with CML. Future follow up of these registry data may demonstrate a decrease in the rate of CVE among nilotinib treated patients, reflecting local adherence to these guidelines. Figure 1 Figure 1. Disclosures Busque: Novartis: Consultancy. Assouline: Eli Lilly: Research Funding; Jewish General Hospital, Montreal, Quebec: Current Employment; Novartis: Honoraria, Research Funding; Amgen: Current equity holder in publicly-traded company, Research Funding; Gilead: Speakers Bureau; Johnson&Johnson: Current equity holder in publicly-traded company; Roche/Genentech: Research Funding; Takeda: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

Diabetes-Associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of the progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease, characterised not only by hyperglycemia but also by various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarises our current knowledge on the epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contributions of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol-lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Epidemiology and prevention of cardiovascular disease

Cardiovascular diseases (CVDs) including coronary artery disease, stroke, heart failure, peripheral arterial disease, and other CVD manifestations comprise the leading causes of morbidity and mortality worldwide. Key risk factors, including hypertension, cigarette smoking, elevated cholesterol, elevated glucose levels/diabetes, obesity, and physical inactivity comprise the top six leading causes of death globally. Prevention of CVD focuses on identifying and managing these and other key risk factors at both the population and individual level through approaches aimed at primordial, primary, and secondary prevention. Global risk factor assessment with short or long-term risk prediction algorithms can help identify those most appropriate for treatment. Novel risk factor evaluation and screening for subclinical CVD can also help further stratify CVD risk. Clinical trials have documented the efficacy of key interventions, including those involving antiplatelet, blood pressure, and lipid modification (from statins and newer non-statin therapies), as well as newer diabetes treatments that reduce CVD risk. Future efforts will best determine what combination of interventions at both the population and individual level can have the greatest impact on prevention of CVD.

DIETARY SPICES AS ANTI-HYPERLIPIDEMIC AGENTS WITH THEIR BIOACTIVE COMPOUNDS FOR CARDIOVASCULAR HEALTH: A REVIEW

Hyperlipidemia is associated with elevated cholesterol and triglyceride levels which is a risk factor for atherosclerosis. Spices being an integral part of culinary culture around the world are known to possess anti-cholesterol compounds and increase the high density lipoprotein cholesterol. This review presents a comprehensive scientific data on the anticholesterol/hypolipidemic activities of various spices used in traditional medicine and cuisine. Bioactive compounds from spices with anti-hyperlipidemic activities and their mode of action are summarized. The findings reaffirm the importance of spices by suggesting their anti-hyperlipdemic/anti-cholesterol activities to prevent cardiovascular diseases.

Current data about localization of acute ischemic stroke and prognostic factors in diabetic and non-diabetic patients

Introduction. Ischemic stroke accounts for approximately 85% of all vascular accidents and has a high number of identified risk factors, including transient ischemic attack, smoking, metabolic syndrome, alcohol consumption, elevated cholesterol levels and artery stenosis carotid. Diabetes mellitus (DM) is a well-established risk factor for ischemic stroke. Material and method. This prospective longitudinal observational study highlights the importance of localization of ischemic stroke, including 340 patients with acute ischemic stroke with / without diabetes mellitus. The database was collected in a Microsoft Excel document. The correlation analysis was processed in the MedCalc 14.1 program where correlation tests included in the program were used. Results. The predominant localization of ischemic stroke in diabetic patients was the middle cerebral artery followed by the posterior cerebral artery and the double localization compared to the group witness where the same trend is maintained (p = 0.22). The correlation between the localization of the acute ischemic stroke with the age 64.5 for MCA, 64.6 for PCA, and 73.57 for DL (CI 95%, p= 0.02). The correlation of the NIHSS severity score with the location of ischemic strokes was also obtained: average NIHSS score 18.9 points for MCA, 18.5 for PCA, 24 for DL (CI 95, p < 0.0001). The data obtained from the Kaplan-Meier analysis on the survival rate of the patients (divided by the vascular territory involved), provided an expected result difference (statistically significant, p < 0.0001). Conclusions. There is no statistically significant difference between diabetic vs. non-diabetic patients regarding the localization correlated with DM, the double location being statistically insignificant between the two batches. The double location having a higher frequency in elderly patients.