Heart rate recovery after exercise and long-term prognosis in patients with coronary artery disease

Background

The long-term prognostic value of heart rate recovery (HRR) has been incompletely documented in patients with coronary artery disease (CAD). We sought to confirm the prognostic value of HRR in a large cohort with stable CAD.

Methods

From the Coronary Artery Surgery Study registry, a database of 24,958 patients with CAD who underwent cardiac catheterization between 1974 and 1979, we identified 4097 patients with baseline exercise stress testing data. HRR was measured at 3 minutes post exercise during a passive recovery. Clinical outcomes were evaluated according to HRR in both threshold and continuous models.

Results

Median long-term follow-up was 14.7 years (interquartile range, 9.8-16.2). HRR < 46 beats per minute (Bpm) most appropriately differentiated nonsurvivors from survivors (area under receiver operating characteristic curve = 0.613) and was associated with an increased risk of all-cause death (adjusted hazard ratio = 1.15; P = 0.011). Increasing HRR was associated with a lower risk of all-cause (adjusted hazard ratio = 0.94 per 10 Bpm; 95% confidence interval, 0.91-0.97; P = 0.0005) and cardiovascular (CV) mortality (adjusted hazard ratio = 0.94 per 10 Bpm; 95% confidence interval, 0.90-0.98; P = 0.003).

Conclusions

HRR at 3 minutes independently predicts long-term all-cause and CV mortality in patients with stable CAD. Measurement of HRR at 3 minutes during passive recovery can be used as a complementary tool to identify patients with a higher total and CV risk.     

Effects of fasting and/or postprandial glucose on heart rate recovery in patients with coronary heart disease

AimThe impact of both fasting and postprandial glycaemia on heart rate recovery (HRR) has not been studied in patients with coronary heart disease (CHD). For this reason, we sought to determine the relationships between HRR and both fasting and postprandial glycaemia.MethodsA total of 4079 patients with baseline fasting plasma glucose (FPG) levels and 706 patients with 2-hour postprandial glucose (2hPG) levels were identified from the Coronary Artery Surgery Study registry, a database of 24,958 patients with suspected or proven CHD who had undergone cardiac catheterization between 1974 and 1979. Median long-term follow-up was 14.7 years (interquartile range: 9.8–16.2 years). The relationships between HRR and both FPG and 2hPG were studied.ResultsIn univariate analyses, increasing levels of both FPG and 2hPG were significantly associated with lower HRR. In multivariate models adjusted for age, exercise tolerance in METs, resting heart rate and maximum systolic blood pressure during exercise testing, FPG remained significantly associated with HRR while 2hPG did not.ConclusionBoth raised FPG and decreased HRR are independent predictors of total and cardiovascular (CV) mortality in subjects with CHD. Our data suggest that the mortality risk associated with elevated FPG may in part be due to deleterious effects on autonomic regulation of CV function, as reflected by lower HRR. Further studies are required to determine whether or not non-pharmacological and/or pharmacological treatments of increased fasting glucose have a beneficial influence on HRR.     

Pharmacological evaluation of the efficacy of <Emphasis Type="Italic">Dysoxylum binectariferum</Emphasis> stem bark and its active constituent rohitukine in regulation of dyslipidemia in rats

The antidyslipidemic effect of the ethanolic extract of Dysoxylum binectariferum stem bark and its major active constituent rohitukine was evaluated in a high fat diet (HFD)-fed dyslipidemic rat model. Chronic feeding of ethanolic extract (200 mg/kg) in HFD-fed rats showed significant lipid lowering activity. The bioassay guided fractionation of ethanolic extract resulted in the identification of known alkaloid rohitukine as major active constituent. Rohitukine (50 mg/kg) significantly decreased the plasma levels of total cholesterol (24 %), phospholipids (25 %), triglycerides (27 %), very low density lipoprotein (27 %) and low density lipoprotein (32 %) accompanied with an increase in high density lipoprotein (21 %). The present study demonstrated that ethanolic extract of Dysoxylum binectariferum stem bark and its major constituent rohitukine both have antidyslipidemic as well as antioxidant potentials. The antidyslipidemic activity of rohitukine can be correlated to its effect on enzymes involved in lipid metabolism.     

Biochemistry and pharmacology of endovanilloids

Endovanilloids are defined as endogenous ligands and activators of transient receptor potential (TRP) vanilloid type 1 (TRPV1) channels. The first endovanilloid to be identified was anandamide (AEA), previously discovered as an endogenous agonist of cannabinoid receptors. In fact, there are several similarities, in terms of opposing actions on the same intracellular signals, role in the same pathological conditions, and shared ligands and tissue distribution, between TRPV1 and cannabinoid CB(1) receptors. After AEA and some of its congeners (the unsaturated long chain N-acylethanolamines), at least 2 other families of endogenous lipids have been suggested to act as endovanilloids: (i) unsaturated long chain N-acyldopamines and (ii) some lipoxygenase (LOX) metabolites of arachidonic acid (AA). Here we discuss the mechanisms for the regulation of the levels of the proposed endovanilloids, as well as their TRPV1-mediated pharmacological actions in vitro and in vivo. Furthermore, we outline the possible pathological conditions in which endovanilloids, acting at sometimes aberrantly expressed TRPV1 receptors, might play a role.     

Identification of 4-isopropyl–thiotropolone as a novel anti-microbial: regioselective synthesis,NMR characterization,and biological evaluation

We have synthesized and separated tosylated thujaplicin isomers for the first time, and elucidated their structures using 1D, 2D-NMR techniques and X-ray crystallography. The tosylated isomers were used to synthesize 4-isopropyl–thiotropolone and 6-isopropyl–thiotropolone in a regioselective manner. ¹H and ¹³C Chemical shifts of synthesized isomers were fully assigned using several NMR experiments, and their isotropic magnetic shielding was calculated using the GIAO (Gauge Including Atomic Orbitals) method and the B3LYP def2-TZVPP level of theory. The calculated chemical shift values were in a good agreement with the experimental results. The biological activity of all synthesized compounds was evaluated against the fungal pathogen Cryptococcus neoformans and four different bacterial strains (Staphylococcus aureus (ATCC 29213), E. coli (ATCC 35218), Acinetobacter baumannii and Pseudomonas aeruginosa (ATCC 27853)). 4-Isopropyl–thiotropolone was found to inhibit Staphylococcus aureus in a low micro molar range and exhibit good therapeutic index and ADME properties. This compound can be used for future lead optimization to design inhibitors against Staphylococcus aureus (ATCC 29213).

4-Isopropyl–thiotropolone was identified as a novel anti-microbial agent with good therapeutic index and ADME properties.     

The burden of diabetes and impaired fasting glucose in India using the ADA 1997 criteria: prevalence of diabetes in India study (PODIS)

This random multistage cross sectional population survey was undertaken to determine the prevalence of diabetes mellitus (DM) and impaired fasting glycemia/glucose (IFG) in subjects aged 25 years and above in India. The study was carried out in 108 centers (49 urban and 59 rural) to reflect the size and heterogeneity of the Indian population. 41,270 (20,534 males and 20,736 females) subjects were studied. 21,516 (10,865 males and 10,651 females) were from urban areas and 19,754 (9669 males and 10,085 females) from rural areas. Blood samples were taken after a fast of 10-12h and the subjects were categorized as having IFG or DM using the 1997 American Diabetes Association criteria. The age and gender standardized prevalence rate for DM and IFG in the total Indian population was 3.3 and 3.6% respectively (P < 0.001). The standardized prevalence of DM and IFG in urban areas was significantly higher than that for the rural population (urban DM prevalence 4.6% versus rural DM prevalence 1.9%, P < 0.001; urban IFG prevalence 4.8% versus rural IFG prevalence 2.5%, P < 0.001). There was no statistically significant difference in the prevalence between DM (4.6%) and IFG (4.8%) in the urban population. The rural prevalence of IFG (2.5%) was significantly (P <0.001) more than the rural prevalence of DM (1.9%). Type 2 diabetes is a major health problem is India.     

Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases

Translocations and deletions of the short arm of chromosome 12 [t(12p) and del(12p)] are common recurring abnormalities in a broad spectrum of hematologic malignant diseases. We studied 20 patients and one cell line whose cells contained 12p13 translocations and/or 12p deletions using fluorescence in situ hybridization (FISH) with phage, plasmid, and cosmid probes that we previously mapped and ordered on 12p12-13. FISH analysis showed that the 12p13 translocation breakpoints were clustered between two cosmids, D12S133 and D12S142, in 11 of 12 patients and in one cell line. FISH analysis of 11 patients with deletions demonstrated that the deletions were interstitial rather than terminal and that the distal part of 12p12, including the GDI-D4 gene and D12S54 marker, was deleted in all 11 patients. Moreover, FISH analysis showed that cells from 3 of these patients contained both a del(12p) and a 12p13 translocation and that the affected regions of these rearrangements appeared to overlap. We identified three yeast artificial chromosome (YAC) clones that span all the 12p13 translocation breakpoints mapped between D12S133 and D12S142. They have inserts of human DNA between 1.39 and 1.67 Mb. Because the region between D12S133 and D12S142 also represents the telomeric border of the smallest commonly deleted region of 12p, we also studied patients with a del(12p) using these YACs. The smallest YAC, 964c10, was deleted in 8 of 9 patients studied. In the other patient, the YAC labeled the del(12p) chromosome more weakly than the normal chromosome 12, suggesting that a part of the YAC was deleted. Thus, most 12p13 translocation breakpoints were clustered within the sequences contained in the 1.39 Mb YAC and this YAC appears to include the telomeric border of the smallest commonly deleted region. Whether the same gene is involved in both the translocations and deletions is presently unknown.     

癌症患者同伴支持量表的汉化及信效度检验

目的 汉化癌症患者同伴支持量表,并检验其信效度。方法 通过正译、回译、文化调试和预调查对原量表进行汉化,形成中文版癌症患者同伴支持量表。于2021年3月—6月选取长沙市2所三级甲等医院的128例青年癌症患者进行问卷调查,分析量表的信效度;2021年7月—2022年3月选取该2所医院招募的241例患者进行问卷调查,用于验证性因子分析。结果 中文版癌症患者同伴支持量表包括3个维度、11个条目。量表水平的内容效度指数为0.948,条目水平的内容效度指数为0.714～1.000。探索性因子分析提取出3个公因子,各条目因子载荷为0.535～0.872,累计方差贡献率为69.64%,方程拟合良好。量表总的Cronbach’s α系数为0.923,折半信度为0.860。验证性因子分析结果 显示,模型拟合度良好。结论 中文版癌症患者同伴支持量表的信效度良好,适用于青年癌症患者同伴支持感的评估。     

Growth factor–heparan sulfate “switches” regulating stages of branching morphogenesis

The development of branched epithelial organs, such as the kidney, mammary gland, lung, pancreas, and salivary gland, is dependent upon the involvement and interaction of multiple regulatory/modulatory molecules, including soluble growth factors, extracellular matrix components, and their receptors. How the function of these molecules is coordinated to bring about the morphogenetic events that regulate iterative tip-stalk generation (ITSG) during organ development remains to be fully elucidated. A common link to many growth factor-dependent morphogenetic pathways is the involvement of variably sulfated heparan sulfates (HS), the glycosaminoglycan backbone of heparan sulfate proteoglycans (HSPG) on extracellular surfaces. Genetic deletions of HS biosynthetic enzymes (e.g., C5-epimerase, Hs2st), as well as considerable in vitro data, indicate that variably sulfated HS are essential for kidney development, particularly in Wolffian duct budding and early ureteric bud (UB) branching. A role for selective HS modifications by enzymes (e.g., Ext, Ndst, Hs2st) in stages of branching morphogenesis is also strongly supported for mammary gland ductal branching, which is dependent upon a set of growth factors similar to those involved in UB branching. Taken together, these studies provide support for the notion that the specific spatio-temporal HS binding of growth factors during the development of branched epithelial organs (such as the kidney, mammary gland, lung and salivary gland) regulates these complex processes by potentially acting as “morphogenetic switches” during the various stages of budding, branching, and other developmental events central to epithelial organogenesis. It may be that two or more growth factor-selective HS interactions constitute a functionally equivalent morphogenetic switch; this may help to explain the paucity of severe branching phenotypes with individual growth factor knockouts.