Abstract 166: Interaction Between LDL and Sympathetic Adrenoreceptors

Introduction: LDL is a significant risk factor for cardiovascular disease and is known to impair flow-dependent vasodilatation. Furthermore, it has been demonstrated that LDL can even directly cause vasoconstricton. Recent studies suggested that lower LDL levels, achieved through administration of statins, are correlated with lower blood pressure, independent from pleiotropic statin effects. Our objective was to investigate whether LDL-induced impairment in flow-dilatation was due to an interaction of LDL with sympathetic adrenoreceptors. Materials and Methods: Flow-dependent isometric tension, intracellularly recorded membrane potential and cAMP-cGMP were measured in segments of 22 coronaries from heart transplantations. Results: As compared to Krebs solution, LDL affected flow-dilatation and caused a relative contraction [Δ(T 3 -T 100 ): Krebs 0.459 g; LDL 0.278 g]. Complete blockade of both α- (phentolamine 10 -7 mol/L) and β-receptors (propranolol 10 -7 mol/L) resulted in a ∼50% reduction of flow-dilatation impairment induced by LDL. Blockage of either α- (1) or β-receptors (2) showed smaller effects which added up to the measured effect under blockade of both receptors (4). Similar effects were apparent in the recorded membrane potential of the vascular smooth muscle cells. Discussion: We conclude that the LDL-induced impairment in flow-dependent dilatation is partially due to the interaction between lipoprotein and both α- and β-adrenoreceptors. Since blockade of each receptor resulted in a relative dilatation, we assume that the LDL effect is caused by a stimulation of α-adrenoreceptors and an inhibition of β-adrenoreceptors.

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Abstract 31: High-density Lipoprotein, a Feed-forward Forechecking Loop

Circulation Research ◽

10.1161/res.117.suppl_1.31 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

A.-l. Behnke ◽

F. Mockenhaupt ◽

K. Willy ◽

K. Winkler ◽

R. Hetzer ◽

...

Keyword(s):

Membrane Potential ◽

Density Lipoprotein ◽

Vascular Wall ◽

Isometric Tension ◽

Diffusion Control ◽

Affinity Constant ◽

Feed Forward ◽

Heart Transplantations ◽

Receptor Sites ◽

Relative Contraction

Background: The protective effect of HDL is projected into the cholesterol back-transport of breakdown products of lipid metabolism to the liver. This is a feed-back circuit which controls cholesterol exit. Cholesterol entry could be safeguarded in a feed-forward forechecking loop at the proteoglycan (PG) receptor sites (syndecan, perlecan). HDL is the counter partner in the system of internalization and diffusion control for lipoprotein entry into the vascular wall. Based on stereochemical and chiral conformity with its PG receptor and the much higher negative charge density, HDL owns by far a higher affinity compared with LDL. Methods: Flow-dependent isometric tension, intracellularly recorded membrane potential and cAMP-cGMP were measured in segments of 25 coronaries from heart transplantations. Results and Discussion: Compared to Krebs solution, LDL (100 mg/dL) impaired flow-dilatation and caused a relative contraction by 18.5% (Table). In contrast, HDL (50 mg/dL) and HDL+LDL stimulated flow-dilatation by 31.1% and 41.4%, respectively (p < 0.96). Thus, the contractile effect of LDL was absent in the Krebs-HDL-LDL solution. The same effects were apparent in the membrane potential and cAMP-cGMP-concentrations of the VSM cells. These results are confirmed by ellipsometry measurements, where nanoplaque formation by LDL is suppressed by preincubation with HDL [Siegel, Malmsten, Ermilov: Adv Coll Interface Sci 205 (2014) 275-318]. Conclusion: LDL-cholesterol entry into the vascular wall is effectfully controlled by HDL in a feed-forward forechecking loop (HDL 4х higher affinity constant to the PG receptor). The interaction between both is dominated by competition.

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Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽

10.1027/0227-5910/a000271 ◽

2014 ◽

Vol 35 (5) ◽

pp. 330-337 ◽

Cited By ~ 14

Author(s):

Cun-Xian Jia ◽

Lin-Lin Wang ◽

Ai-Qiang Xu ◽

Ai-Ying Dai ◽

Ping Qin

Keyword(s):

Risk Factor ◽

Family Income ◽

Rural China ◽

Significant Risk ◽

Significant Risk Factor ◽

Health Condition ◽

Physical Illness ◽

Rural Residents ◽

Increased Risk ◽

Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

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Baroreflex Sensitivity Assessment – Latest Advances and Strategies

European Cardiology Review ◽

10.15420/ecr.2011.7.2.89 ◽

2011 ◽

Vol 7 (2) ◽

pp. 89 ◽

Cited By ~ 20

Author(s):

Maria Teresa La Rovere ◽

Roberto Maestri ◽

Gian Domenico Pinna ◽

◽

...

Keyword(s):

Baroreflex Sensitivity ◽

Carotid Sinus ◽

Lower Blood Pressure ◽

Vasomotor Tone ◽

Sensitivity Assessment ◽

Lower Blood ◽

Prognostic Implications ◽

Novel Therapeutic Strategies ◽

Sympathetic Vasomotor Tone ◽

Stimulation Of

The baroreflex mechanism has been recognised as a key part of cardiovascular regulation. Alterations in the baroreceptor-heart rate reflex (baroreflex sensitivity [BRS]) contribute to sympathetic–parasympathetic imbalance, playing a major role in the development and progression of many cardiovascular disorders. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients. This article reviews the most relevant advances for the measurement of BRS and their clinical and prognostic implications. Novel therapeutic strategies, exploring the use of electrical stimulation of the carotid sinus, have been evaluated recently in experimental and preliminary clinical studies to lower blood pressure and to reduce the level of baroreflex-mediated sympathoexcitation in heart failure. A recent study has also shown that the implementation of an artificial baroreflex system to regulate sympathetic vasomotor tone automatically is feasible.

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Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers

BMC Gastroenterology ◽

10.1186/s12876-020-01580-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Junya Arai ◽

Jun Kato ◽

Nobuo Toda ◽

Ken Kurokawa ◽

Chikako Shibata ◽

...

Keyword(s):

Risk Factors ◽

Activities Of Daily Living ◽

Daily Living ◽

Poor Prognosis ◽

Significant Risk ◽

Care Facility ◽

Significant Risk Factor ◽

Advanced Age ◽

Gastroduodenal Ulcers ◽

Poor Outcomes

Abstract Background Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. Methods In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. Results Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08–16.2), and heart disease (OR 3.05; 95% CI 1.11–8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36–28.7). Conclusion In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

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Neurodevelopmental outcome of healthy term newborn with serum bilirubin >15 mg/dl at one year

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-200511 ◽

2020 ◽

pp. 1-6

Author(s):

P. Dubey ◽

J. Shrivastava ◽

B.P. Choubey ◽

A. Agrawal ◽

V. Thakur

Keyword(s):

Serum Bilirubin ◽

Tertiary Care ◽

Neurodevelopmental Outcome ◽

Significant Risk ◽

Central India ◽

Significant Risk Factor ◽

Motor Domain ◽

Medical Emergency ◽

One Year ◽

Group 1

BACKGROUND: Neonatal hyperbilirubinemia is a common medical emergency in early neonatal period. Unconjugated bilirubin is neurotoxic and can lead to lifelong neurological sequelae in survivors. OBJECTIVE: To find out the association between serum bilirubin and neurodevelopmental outcome at 1 year of age using Development Assessment Scale for Indian Infants (DASII). METHODS: A prospective cohort study was conducted in the Department of Pediatrics of a tertiary care institution of Central India between January 2018 and August 2019. Total 108 term healthy neonates, with at least one serum bilirubin value of >15 mg/dl, were included. Subjects were divided into three groups based on the serum bilirubin; group 1: (15–20 mg/dl) –85(78.7%) cases, group 2: (20–25 mg/dl) –17(15.7%), and group 3: (>25 mg/dl) –6(5.5%). Developmental assessment was done using DASII at 3, 6, 9, 12 months of age. RESULTS: Out of 108 cases, 101(93.5%) received phototherapy, and 7(6.5%) received double volume exchange transfusion. Severe delay was observed in 5(4.6%) and mild delay in 2(1.9%) cases in the motor domain of DASII at one year. Severe delay in the motor domain was associated with mean TSB of 27.940±2.89 mg/dl and mild delay with mean TSB of 22.75±1.76 mg/dl (p = 0.001). On cluster analysis, delay was observed in locomotion 1 score in 11(13%) cases (p = 0.003) and manipulation score in 6(7.1%) cases in group 1. CONCLUSION: Increased serum bilirubin was a significant risk factor for the delayed neurodevelopment in babies with neonatal jaundice. Even a moderate level of bilirubin significantly affects the developmental outcome.

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Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

Scientific Reports ◽

10.1038/s41598-021-91800-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Chun Huang ◽

Po-Tseng Lee ◽

Mu-Shiang Huang ◽

Pei-Fang Su ◽

Ping-Yen Liu

Keyword(s):

Risk Factor ◽

Dose Response ◽

Cox Model ◽

Significant Risk ◽

Significant Risk Factor ◽

Cardiovascular Death ◽

Specific Model ◽

Distribution Model ◽

All Cause Mortality ◽

Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

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The Role of Past Suicidal Behavior on Current Suicidality: A Retrospective Study in the Israeli Military

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18020649 ◽

2021 ◽

Vol 18 (2) ◽

pp. 649

Author(s):

Leah Shelef ◽

Jessica M Rabbany ◽

Peter M Gutierrez ◽

Ron Kedem ◽

Ariel Ben Yehuda ◽

...

Keyword(s):

Suicide Attempt ◽

Suicidal Behavior ◽

Military Service ◽

Suicide Ideation ◽

Rating Scale ◽

Suicide Attempts ◽

Significant Risk ◽

Significant Risk Factor ◽

Severity Rating ◽

Significant Difference

Past suicide attempts are a significant risk factor for future suicidality. Therefore, the present military-based study examined the past suicidal behavior of soldiers who recently made a severe suicide attempt. Our sample consisted of 65 active-duty soldiers (61.5% males), between the ages of 18 and 28 years old (M = 20.4, SD ± 1.3). The inclusion criterion was a recent severe suicide attempt, requiring at least a 24 h hospitalization. This sample was divided into two groups, according to previous suicidal behavior, namely whether their first suicide attempt was before or after enlistment (n = 25; 38.5% and n = 40; 61.5%, respectively). We then examined the lethality and intent of the recent event in regard to this division. Four measures were used to assess the subjects’ suicidal characteristics: the Columbia Suicide Severity Rating Scale, the Self-Harm Behavior Questionnaire, the Suicidal Behaviors Questionnaire-Revised, and the Beck Scale for Suicide Ideation. No significant difference in the severity of the suicide attempts (either actual or potential severity) were found between those who had suicide attempts before enlistment and those who had their first attempt in the service. As a matter of fact, most of the suicide attempts that occurred for the first time during military service had used a violent method (58.3%, n = 21). Finally, using multivariate analyses, we found that current thoughts and behavior, rather than past suicidality, was the strongest predictor for the lethality of suicide attempts.

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Umbilical cord blood therapy modulates neonatal hypoxic ischemic brain injury in both females and males

Scientific Reports ◽

10.1038/s41598-021-95035-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tayla R. Penny ◽

Yen Pham ◽

Amy E. Sutherland ◽

Joohyung Lee ◽

Graham Jenkin ◽

...

Keyword(s):

Brain Injury ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Significant Risk ◽

Immunohistochemical Analysis ◽

Significant Risk Factor ◽

Tissue Loss ◽

Artery Ligation ◽

Rat Pups

AbstractPreclinical and clinical studies have shown that sex is a significant risk factor for perinatal morbidity and mortality, with males being more susceptible to neonatal hypoxic ischemic (HI) brain injury. No study has investigated sexual dimorphism in the efficacy of umbilical cord blood (UCB) cell therapy. HI injury was induced in postnatal day 10 (PND10) rat pups using the Rice-Vannucci method of carotid artery ligation. Pups received 3 doses of UCB cells (PND11, 13, 20) and underwent behavioural testing. On PND50, brains were collected for immunohistochemical analysis. Behavioural and neuropathological outcomes were assessed for sex differences. HI brain injury resulted in a significant decrease in brain weight and increase in tissue loss in females and males. Females and males also exhibited significant cell death, region-specific neuron loss and long-term behavioural deficits. Females had significantly smaller brains overall compared to males and males had significantly reduced neuron numbers in the cortex compared to females. UCB administration improved multiple aspects of neuropathology and functional outcomes in males and females. Females and males both exhibited injury following HI. This is the first preclinical evidence that UCB is an appropriate treatment for neonatal brain injury in both female and male neonates.

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Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus

Children ◽

10.3390/children8050417 ◽

2021 ◽

Vol 8 (5) ◽

pp. 417

Author(s):

Moon Bae Ahn ◽

Kyoung Soon Cho ◽

Seul Ki Kim ◽

Shin Hee Kim ◽

Won Kyoung Cho ◽

...

Keyword(s):

Glycosylated Hemoglobin ◽

Significant Risk ◽

Area Under The Curve ◽

Kidney Injury ◽

Significant Risk Factor ◽

Controlled Study ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Diabetic Children ◽

Kidney Injury Molecule 1 ◽

Neutrophil Gelatinase

Diabetic nephropathy (DN) is a serious microvascular complication in childhood diabetes and microalbuminuria has been a solid indicator in the assessment of DN. Nevertheless, renal injury may still occur in the presence of normoalbuminuria (NA) and various tubular injury biomarkers have been proposed to assess such damage. This case-controlled study aimed to evaluate plasma and urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 (KIM-1) levels in diabetic children particularly in those with normo- and high-NA stages and determine their role in predicting DN. Fifty-four children/adolescents with type 1 and 2 diabetes and forty-four controls aged 7–18 years were included. The baseline clinical and laboratory characteristics including plasma and urinary biomarkers were compared. The plasma KIM-1 levels were significantly higher in diabetic children than in the controls and in high-NA children than normo-NA children. Glycosylated hemoglobin (HbA1c) was identified as a significant risk factor for increased plasma KIM-1. The optimal cutoff for HbA1c when the plasma KIM-1 was > 23.10 pg/mL was 6.75% with an area under the curve of 0.77. For diabetic children with mildly increased albuminuria, the plasma KIM-1 complementary to MA may help increase the yield of detecting DN. Our findings also suggested an HbA1c cutoff of 6.75% correlated with increased plasma KIM-1.

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