Angiotension-converting Enzyme Research Articles

Formulation and Evaluation of Lisinopril Double Layer Tablet

Lisinopril is an antihypertensive drug that is primarily used in the treatment of hypertension, congestive heart failure, heart attacks and also in preventing renal and retinal complication of diabetes that acts by inhibiting angiotension converting enzyme (ACE). The present investigation deals with the formulation of lisinopril double layer tablet containing 100 mg fast release layer and 100 mg sustained release layer to be formulated using wet granulation method. Twelve formulations are prepared for bilayered tablets; 6 formulas for fast release layer study (FF1 to FF6) and another 6 formulas for the sustained release layer study. Friability of all formulation was less than 1%, which indicates the tablets had good mechanical resistance. Drug content was found to be uniform in all formulas. The tablet thickness was found to be 5.12 to 5.31 mm. Acceptable weight variation and content uniformity. Hardness was low for fast release lisinopril layer formulas FF1 to FF6, while it was high for formulas used to study the sustained release layer (SF1 to SF6). On the other hand disintegration time was short for formulas containing super disintegrant as crospovidone 15, and 10 seconds, croscarmelose 27, and 24 seconds and sodium starch glycolate 24, and 19 seconds and the shortest time for disintegration was for crospovidone containing formulas (FF1, and FF4); 15, and 10 seconds respectively for fast release layer study with no disintegration for the formulas used to study the sustained release of lisinopril. At the same time the release study for formulas containing crospovidone was within 20 minutes, while formulas containing HPMC K100 was 12 hours release. To be concluded that double layer tablets were attempted to be prepared for controlled drug delivery. The first layer of lisinopril provides the initial drug release while the second layer provides sustained release of lisinopril for increase patient compliance and decrease frequency of dosing for more control of hyper tension.

The Candidate Molecules, RBD-ACE2 Binding Inhibitors to Prevent Sars-CoV-2 Infection

Angiotension-converting enzyme 2 (ACE2) is the host receptor of the serious-acute respiratory syndrome coronavirus 2 (Sars-CoV-2) spike protein. In this article, the interaction of ACE2 with the receptor binding domains (RBD) of Wuhan-Hu-1 and United Kingdom (UK) and South African (SA) variants is examined in silico. Their Gibbs free energies were computed using a protein binding energies prediction model. The interaction characteristics of RBDs with possible inhibitory compounds as well as a standard drug, Paxlovid, were also investigated, and Gibbs free energies were computed. Molecular modeling, molecular dynamics and molecular docking methods were employed and the results are compared and discussed.

Pre-Existing Pancreatitis and Elevated Risks of COVID-19 Severity and Mortality

Pre-Existing Pancreatitis and Elevated Risks of COVID-19 Severity and Mortality

Analysis of the active components and mechanism of Shufeng Jiedu capsule against COVID-19 based on network pharmacology and molecular docking.

This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.

Relation between pre-procedural increase in urinary albumin excretion and changes in estimated glomerular filtration rate after coronary angiography in diabetic patients

Abstract Background Contrast-induced nephropathy (CIN), is an acute impairment in renal function, and typically occurs within 3 days following the exposure to a contrast medium (CM). It is associated with increased hospital stay and increased morbidity and mortality, Adult patients with diabetes have a higher risk than the general population for developing contrast induced nephropathy. Methods The current study includes 40 patients with diabetes mellitus, scheduled for coronary angiography with estimated GFR >60 ml/min .the patients were divided according to their pre-procedural urinary albumin creatinine ratio (ACR) results into 3 groups: Group 1 included patients with pre-procedure urinary albumin creatinine ratio < 30mg/g, Group 2 included patients with pre- procedure albumin creatinine ratio 30- 300 mg/g and Group 3 included patients with pre-procedure albumin creatinine ratio >300 mg/g . Estimated GFR (glomerular filtration rate) calculated using MDRD and serum creatinine were measured at day 2 and 3 (Day +2 +3) after coronary angiography. Results There was no statistically significant difference in the age and gender distribution, the use of ACEIs (angiotension converting enzyme inhibitors) or diuretics between the cases who developed and who didn’t develop CIN. The mean ACR in the group with no contrast induced nephropathy was 225.38 ± 209.53 which was statistically significantly lower when compared with the cases with contrast induced nephropathy (420.43± 348.52) (p = 0.033). The mean HbA1c in no contrast induced nephropathy group was 7.11 ± 0.64 and in contrast induced nephropathy group it was 9.09 ± 0.66 which is significantly higher (P > 0.001).With univariate regression analysis, ACR, HbA1c and number of vessels affected were shown to be risk factors for occurrence of CIN after use of contrast, but with multivariate analysis, both ACR and HbA1c were shown to be risk factors for CIN. Conclusion An increase in albumin creatinine ratio in itself can be a risk factor for development of contrast induced nephropathy in diabetic patients.

ACE ID gene polymorphism contributes to chronic kidney disease progression but not NOS3 gene among Type 2 diabetes with nephropathy patients

AimDiabetic nephropathy (DN) is one of the major life-threatening complications of diabetes and it leads to end-stage renal disease. Altered angiotension converting enzyme and nitric oxide synthase are probably the cause of initiation and the progression of diabetic nephropathy. The present study aims to investigate the effect of ACE ID and NOS3 VNTR gene polymorphisms on the progression of chronic kidney disease among diabetic nephropathy. Methods253 DN patients and 104 controls were genotyped for ACE ID and NOS3 VNTR polymorphisms by following PCR-RFLP method. The diabetic nephropathy cases were divided into two groups based on CKD stages: 138 DN cases were at early stage (CKD1 to CKD3) and 115 DN cases were at advanced stage (CKD4 and CKD5). Association χ2 and univariate analysis were performed. ResultsA significant difference was found in genotype frequencies of ACE ID and NOS3 VNTR polymorphisms between the DN patients and the controls. On univariate analysis, the DD genotype of ACE gene was found to have a significant association with the advancement of CKD in DN (OR=0.37; 95 % CI=0.14–0.94; p=0.033). ConclusionsThe results suggest the association of ACE ID and NOS3 VNTR polymorphism with diabetic nephropathy in South Indian population. Furthermore, the present study evidences the association between DD genotype of ACE gene and advancement of CKD progression in DN.

Synthesis and Characterization of Aminophosphonate Containing Chitosan Polymer Derivatives: Investigations of Cytotoxic Activity and in Silico Study of SARS-CoV-19

Chitosan is broadly used as a biological material since of its excellent biological activities. This work describes investigations of chitosan interaction with SARS-CoV-2, which is occupied by human respiratory epithelial cells through communication with the human angiotension-converting enzyme II (ACE2). The β-chitosan derivatives are synthesized and characterized by FT-IR, nuclear magnetic resonance (1H and 13C NMR), mass spectrometry, X-ray diffraction, TGA, DSC, and elemental analysis. The β-chitosan derivatives were screened for cytotoxic activity against the HepG2 and MCF-7 (breast) cancer cell lines. Compound 1h (GI50 0.02 µM) is moderately active against the HepG2 cancer cell line, and Compound 1c is highly active (GI50 0.01 µM) against the MCF-7 cancer cell line. In addition, chitosan derivatives (1a–1j) docking against the SARS coronavirus are found by in-silico docking analysis. The findings show that compound 1c exhibits notable inhibition ability compared with other compounds, with a binding energy value of −7.9 kcal/mol. Based on the molecular docking results, the chitosan analog is proposed to be an alternative antiviral agent for SARS-CoV2.

Immunogenetic Predictors of Severe COVID-19.

According to an analysis of published data, only 20% of patients with the new coronavirus infection develop severe life-threatening complications. Currently, there are no known biomarkers, the determination of which before the onset of the disease would allow assessing the likelihood of its severe course. The purpose of this literature review was to analyze possible genetic factors characterizing the immune response to the new coronavirus infection that could be associated with the expression of angiotension-converting enzyme 2 (ACE-2) and related proteins as predictors of severe Corona virus disease 2019 (COVID-19). We analyzed original articles published in Medline, PubMed and Scopus databases from December 2019 to November 2020. For searching articles, we used the following keywords: New coronavirus infection, Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), COVID-19, severe course, complications, thrombosis, cytokine storm, ACE-2, biomarkers. In total, 3714 publications were selected using the keywords, of which 8 were in congruence with all the criteria. The literature analysis of the association of immunogenic characteristics and the expression of ACE-2 and related proteins with the development of severe COVID-19 revealed following genetic factors: HLA-B*46:01 genotype, CXCR6 gene hypoexpression, CCR9 gene expression, TLR7, rs150892504 mutations in the ERAP2 gene, overexpression of wild-type ACE-2, TMPRSS2 and its different polymorphisms. Genes, associated with the severe course, are more common among men. According to the analysis data, it can be assumed that there are population differences. However, the diagnostic significance of the markers described must be confirmed with additional clinical studies.

The Relation between Pre-Procedural Increase in Urinary Albumin Excretion and Changes in Estimated Glomerular Filtration Rate after Coronary Angiography in Diabetic Patients

Background: Contrast-induced nephropathy (CIN), is an acute impairment in renal function, and typically occurs within 3 days following the exposure to a iodinated contrast medium (CM). It is associated with increased hospital stay and increased morbidity and mortality. Adult patients with diabetes have a higher risk than the general population for developing contrast-induced nephropathy. Objective: To assess the significance of preprocedural microalbuminuria on renal function changes post coronary angiography. Patients and methods: The current study included 40 patients all over the age of 18 years, with diabetes mellitus type 1 or type 2, scheduled for coronary angiography with estimated GFR > 60 ml/min. Results: incidence of contrast-induced nephropathy in this study was 40 % (n=16) of patients while 60% (n = 24) did not fit the definition of CIN. There was no statistically significant difference in the age, gender distribution and use of angiotension converting enzyme inhibitors (ACEIs) or diuretics between the cases who developed and who did not develop CIN. The mean albumin creatinine ratio (ACR) in the group with no contrast induced nephropathy was 225.38 ± 209.53 which was statistically significantly lower when compared to the cases with contrast-induced nephropathy (420.43 ± 348.52) (p = 0.033). The mean HbA1c in no contrast-induced nephropathy group was 7.11 ± 0.64 and in contrast induced nephropathy group it was 9.09 ± 0.66, which was significantly higher (P > 0.001). With univariate regression analysis, ACR, HbA1c and number of vessels affected were shown to be risk factors for occurrence of CIN after use of contrast, but with multivariate analysis, both ACR and HbA1c were shown to be risk factors for CIN. Conclusion: An increase in urinary albumin creatinine ratio in itself maybe be a risk factor for development of contrast-induced nephropathy in diabetic patients.

Going beyond the mean: economic benefits of myocardial infarction secondary prevention

BackgroundUsing the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account.MethodsSwiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12 inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis.ResultsOnly 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (− 4865 Swiss Francs [95% confidence interval − 8027; − 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median.ConclusionsCompliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone.

Immunohistochemical Study of SARS-CoV-2 Viral Entry Factors in the Cornea and Ocular Surface.

To confirm the ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by evaluating the expression of viral entry factors in human ocular tissues using immunohistochemistry. Fresh donor corneas and primary explant cultures of corneal, limbal, and conjunctival epithelial cells were evaluated for the expression of viral entry factors. Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). In total, 5 donor corneas were evaluated for the expression of viral entry factors. In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. DC-SIGN/DC-SIGNR expression varied between donor specimens. Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium. Cultured corneal, limbal, and conjunctival epithelial cells mimic the expression of viral entry factors in fresh donor tissue and may be useful for future in vitro SARS-CoV-2 infection studies.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy.

ObjectiveTo select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.MethodsThe three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.ResultsIt was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.ConclusionsA class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

COVID-19 and diabetes: The why, the what and the how

BackgroundThe novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. MethodsA search using keywords “COVID-19” and “Diabetes” was performed using different sources, including PubMed and World Health Organization. ResultsCOVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. ConclusionCOVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.

Angiotension converting enzyme 2 in the context of 2019 novel coronavirus infection：friend or foe？

2019 novel coronavirus(2019-nCoV) epidemic broke out in Wuhan, Hubei In December 2019. Angiotension converting enzyme 2(ACE2) has been identified as a receptor of 2019-nCoV, which combines with ACE2 by acanthoid glycoprotein in host respiratory epithelial cells. On the other hand, ACE2 has a positive therapeutic effect on a variety of atherosclerotic cardiovascular diseases (ASCVD) and acute lung injury including SARS. Therefore, whether ACE2 is an enemy or a friend of human beings in the context of 2019-nCoV epidemic has become a controversial topic. Based on the related researches of ACE2, this paper analyzes the problem deeply and puts forward the research prospect, hoping to be helpful for the recognition and prevention of 2019-nCoV infection. Key words: SARS-CoV-2; ACE2; Renin-angiotension system

Current status of drug development against SARS CoV-2 infections

SARS CoV-2 and its associated disease Covid-19 first occurred in China at the end of 2019 and conquered the world in a storm. As of June 24, 2020, the World Health Organization listed 9,129,146 confirmed cases, accompanied by 473,797 deaths. An initial response by many countries was to lock down their economies, which helped flattening the curve at a high economic cost. The long-term solution will be vaccines to prevent infection and treatment drugs.             This minireview focuses on drugs against the virus itself. Among the drugs that interfere with the virus’ ability to attach to and invade the human cell, camostat mesylate looks promising in vitro, but clinical trials have not been completed yet. A phase II trial has been completed for recombinant human angiotension converting enzyme 2 that blocks the spike protein from binding to cellular ACE-2. Hydroxychloroquine is probably the most controversial of all drugs; after initial excitement, the Federal Drug Administration revoked the emergency use of this drug against SARS CoV-2. Among the inhibitors of the RNA dependent RNA polymerase of the virus, remdesivir, faripiravir which is already in a phase IV trial, and tenofovir will be discussed. Additional drugs included in this study are lopinavir/ritonavir that have previously been used against HIV and the antiparasitic drug ivermectin. Many of the presented drugs have previously been used for a different disease and are currently being trialed against SARS CoV-2.

Regional practice norms for the care of childhood cancer survivors at risk for cardiomyopathy: A Delphi study.

Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.

Optimizing Pulmonary Artery Pressures with use of Ivabradine in Cardiomyopathy

Case reportPatient is a 42 yr old male with past medical history of chronic systolic heart failure, nonischemic cardiomyopathy since 2011, felt to be secondary to chronic prescription anabolic steroid use, EF 10-15%, history of cardiac arrest due to hyperkalemia, ICD single-chamber, hypertension, and chronic kidney disease stage III. Based on right heart cath and cardiopulmonary stress test, the patient is too good for advanced heart failure therapies. He is a NYHA II and is managed on carvedilol 25mg po BID, lisinopril 5 mg po daily, ivabradine 7.5mg po BID. On 2/13/18, patient ran out of his ivabradine. The following day his heart rate started to increase to the mid 90s from a baseline of 70s . It took two days for his diastolic pulmonary artery pressure (PAd) to increase above his set threshold of 15-20mmHg after stopping the ivabradine. He was able to restart ivabradine on 2/20/18 and his heart rate came back to the 70s and his PAd dropped back below 20 mmHg.ConclusionOptimizing PAd can be influenced by many factors including hypervolemia, hypovolemia, blood pressure, and heart rate. In many cases, optimizing heart failure medications such as the betablockers and angiotension converting enzyme inhibitors can help optimize PAd, however controlling blood pressure and heart rate are important also. In this case study, using ivabradine to reduce heart rate shows a significant improvement in PAd without adjusting diuretics or other heart failure medications. Patient is a 42 yr old male with past medical history of chronic systolic heart failure, nonischemic cardiomyopathy since 2011, felt to be secondary to chronic prescription anabolic steroid use, EF 10-15%, history of cardiac arrest due to hyperkalemia, ICD single-chamber, hypertension, and chronic kidney disease stage III. Based on right heart cath and cardiopulmonary stress test, the patient is too good for advanced heart failure therapies. He is a NYHA II and is managed on carvedilol 25mg po BID, lisinopril 5 mg po daily, ivabradine 7.5mg po BID. On 2/13/18, patient ran out of his ivabradine. The following day his heart rate started to increase to the mid 90s from a baseline of 70s . It took two days for his diastolic pulmonary artery pressure (PAd) to increase above his set threshold of 15-20mmHg after stopping the ivabradine. He was able to restart ivabradine on 2/20/18 and his heart rate came back to the 70s and his PAd dropped back below 20 mmHg. Optimizing PAd can be influenced by many factors including hypervolemia, hypovolemia, blood pressure, and heart rate. In many cases, optimizing heart failure medications such as the betablockers and angiotension converting enzyme inhibitors can help optimize PAd, however controlling blood pressure and heart rate are important also. In this case study, using ivabradine to reduce heart rate shows a significant improvement in PAd without adjusting diuretics or other heart failure medications.

Fermente Süt Ürünlerinin Kan Basıncını Düşürücü Etkisi

Hypertension (HTN) is a major risk factor for the development of cardiovascular
 diseases. Therefore, there is a need to lower blood pressure (BP) to reduce the
 risk of these degenerative diseases. Fermented milks contain several potential
 factors that can lower BP including calcium and microbial metabolites
 particularly the angiotension-converting enzyme (ACE) inhibitory peptides and
 γ-aminobutyric acid.  Animal studies
 clearly demonstrated the BP lowering effect of fermented milk while results
 from clinical trials were controversial due to a large number of variables that
 should be considered in clinical trials. An overview on the antihypertensive effect
 of fermented milk products is presented and discussed in this review.

Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications

AbstractBiocatalysts originating from Badamu (Prunus communis) have been applied to catalyze the asymmetric synthesis of (R)‐4‐methylsulfanylmandelonitrile, a key building block of thiamphenicol and florfenicol. Here, four hydroxynitrile lyase (HNL) isozymes from Badamu were cloned and heterologously expressed in Pichia pastoris. The biochemical properties and catalytic performances of these isozymes were comprehensively explored to evaluate their efficiency and selectivity in asymmetric synthesis. Among then, PcHNL5 was identified with outstanding activity and enantioselectivity in asymmetric hydrocyanation. Under the optimized mild biphasic reaction conditions, seventeen prochiral aromatic aldehydes were converted to valuable chiral cyanohydrins with good yields (up to 94%) and excellent optical purities (up to >99.9% ee), which provide a facile access to numerous chiral amino alcohols, hypoglycemic agents, angiotension converting enzyme (ACE) inhibitors and β‐blockers. This work therefore underlines the importance of discovering the most potent biocatalyst among a group of isozymes for converting unnatural substrates into value‐added products.magnified image

SAFETY OF ENALAPRIL IN INFANTS: DATA FROM THE PEDIATRIC HEART NETWORK INFANT WITH SINGLE VENTRICLE TRIAL

Background: Angiotension converting enzyme (ACE) inhibitor therapy has been shown to improve ventricular function and clinical outcomes in adult patients with heart failure. Despite the lack of safety and efficacy data, empiric use of ACE inhibitor therapy is common in infants and children with