The Effect of Jeo Dang‐Tang on Cytokines Production in the Patients with Cerebral Infarction

Abstract

The herbal formulation “Jeo Dang‐Tang” (JDT) has long been used for various cerebrovascular diseases. However, very little has scientific investigation been carried out. The aim of the present study is to investigate the effect of JDT on the production of various cytokines in the patients with cerebral infarction (CI). Peripheral blood mononuclear cells (PBMC) obtained from the patients with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The amount of interleukin (IL)‐4, IL‐10 and transforming growth factor (TGF)‐1β, in culture supernatant, was significantly increased in the JDT, LPS or PHA treated cells compared to unstimulated cells (P < 0.05). We also show that increased IL‐4, and IL‐10 level by LPS or PHA was significantly inhibited by JDT in a dose‐dependent manner. Maximal inhibition rate of IL‐4 and IL‐10 production by JDT was 45 ± 2% and 51 ± 5% for LPS‐stimulated cell and 41.5 ± 3% and 70.8 ± 2% for PHA‐stimulated cells, respectively (P < 0.05). On the other hand, JDT significantly increased the LPS or PHA‐induced TGF‐β1 production (P < 0.05). These data suggest that JDT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.     

Effect of Physical Training on Blood Level of Endogenous Modulators of β-Adreno- and μ-Cholinoreactivity in Patients with a History of Myocardial Infarction

The relative content of myocyte-active factors and endogenous muscarinic receptor blocker in the blood increased, while the concentration of endogenous -adrenoceptor sensitizer decreased in coronary patients with a history of acute myocardial infarction. Physical training produced a therapeutic effect, normalized the content of these factors and, probably, improved -adrenergic and muscarinic cholinergic regulation of the heart and vessels.     

Can Saliva Proteins Be Used to Predict the Onset of Acute Myocardial Infarction among High-Risk Patients?

Human saliva plays a pivotal role in digesting food and maintaining oral hygiene. The presence of electrolytes, mucus, glycoproteins, enzymes, antibacterial compounds, and gingival crevicular fluid in saliva ensures the optimum condition of oral cavity and general health condition. Saliva collection has been proven non-invasive, convenient, and inexpensive compared to conventional venipuncture procedure. These distinctive advantages provide a promising potential of saliva as a diagnostic fluid. Through comprehensive analysis, an array of salivary proteins and peptides may be beneficial as biomarkers in oral and systemic diseases. In this review, we discuss the utility of human salivary proteomes and tabulate the recent salivary biomarkers found in subjects with acute myocardial infarction as well as respective methods employed. In a clinical setting, since acute myocardial infarction contributes to large cases of mortality worldwide, an early intervention using these biomarkers will provide an effective solution to reduce global heart attack incidence particularly among its high-risk group of type-2 diabetes mellitus patients. The utility of salivary biomarkers will make the prediction of this cardiac event possible due to its reliability hence improve the quality of life of the patients. Current challenges in saliva collection are also addressed to improve the quality of saliva samples and produce robust biomarkers for future use in clinical applications.     

Proteolytic Enzymes Activities in Patients After Myocardial Infarction Correlate with Serum Concentration of TGF-β

Myocardial infarction (MI) is caused by occlusion of coronary artery and insufficient oxygen supply to a certain area of myocardium. Its necrosis appears as a result of MI. The process of tissue repair after MI is very complicated and it is influenced by numerous factors, including growth factors and proteolytic enzymes. The aim of the study was to determine serum transforming growth factor β (TGF-β) concentration on day 2 and 7 after MI and to asses the relationship of this growth factor with serum proteolytic activity of collagenase and elastase. In addition, the effect of fibrynolytic treatment on these factors was evaluated. About 100 patients with MI were enrolled to the study. The control group consisted of 50 healthy individuals. We observed that TGF-β1 concentration correlated positively with collagenase activity on the second day after MI and that it also correlated positively with elastase activity on day 2 and 7 after MI. Moreover, treatment with streptokinase (SK) caused a significant increase of TGF-β serum concentration. Our data indicate that TGF-β1 may be one of the factors involved in tissue repair process after MI. Its effect seems to be mediated by collagenase and elastase and may change with the time that elapsed after MI.     

Right Ventricular and Right Atrial Involvement Can Predict Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy?

Objectives and Background: Atrial fibrillation (AF) is associated with clinical deterioration, stroke and disability in patients with hypertrophic cardiomyopathy (HCM). Therefore, the objective of this study was to evaluated cardiac magnetic resonance (CMR)-derived determinants for the occurrence of AF in patients with HCM.Methods: 98 Patients with HCM and 30 healthy controls underwent CMR and were followed-up for 6±3 years.Results: 19 (19.4%) patients presented with AF at initial diagnosis, 19 (19.4%) developed AF during follow-up and 60 (61.2%) remained in sinus rhythm (SR). Compared to healthy controls, patients with HCM who remained in SR presented with significantly increased left ventricular mass, an elevated left ventricular remodeling index, enlarged left atrial volumes and reduced septal mitral annular plane systolic excursion (MAPSE) compared to healthy controls. Whereas HCM patients who presented with AF at initial diagnosis and those who developed AF during follow-up additionally presented with reduced tricuspid annular plane systolic excursion (TAPSE) and right atrial (RA) dilatation. Receiver-operator curve analysis indicated good predictive performance of TAPSE, RA diameter and septal MAPSE (AUC 0.73, 0.69 and 0.71, respectively) to detect patients at risk of developing AF.Conclusion: Reduced MAPSE measurements and enlarged LA volumes seems to be a common feature in patients with HCM, whereas reduced TAPSE and RA dilatation only seem to be altered in patients with history of AF and those developing AF. Therefore, they could serve as easy determinable markers of AF in patients with HCM.     

The Effect of SHJKS on Cytokines Production and NF-κB Activation in the Peripheral Blood Mononuclear Cells of Patients with Cerebral Infarction

The Korean genuine medicine “Seonghyangjeongkisan” (SHJKS) has long been used for various cerebrovascular diseases. However, very little scientific investigation has been carried out. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of cerebral infarction (CI). The aim of the present study is to elucidate how SHJKS modulates the inflammatory reaction in lipopolysaccaride (LPS) plus phytohaemagglutinin (PHA)-stimulated peripheral mononuclear cells (PBMCs) from CI patients. The amount of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 in PBMC culture supernatant was significantly increased in the LPS plus PHA treated cells compared to unstimulated cells. SHJKS inhibited the TNF-α, IL-1β, IL-6, and IL-8 production in dose dependent manner. Maximal inhibition rate of the TNF-α, IL-1β, IL-6, and IL-8 by SHJGS (1.0 mg/ml) was 68.01 ± 0.28% (P < 0.01), 52.11 ± 0.56 % (P < 0.01), 53.42 ± 0.46 % (P < 0.01), and 46.70 ± 0.37% (P < 0.05), respectively. In addition, we show that SHJKS suppressed nuclear factor (NF)-κB activation induced by LPS plus PHA, leading to suppression of IκB-α phosphorylation and degradation. These results suggest that SHJKS might have regulatory effects on LPS plus PHA-induced cytokine production and NF-κB activation, which might explain its beneficial effect in the treatment of CI.     

Effect of 45° Reclining Sitting Posture on Swallowing in Patients with Dysphagia

Purpose

To determine the effect of a 45° reclining sitting posture on swallowing in patients with dysphagia.

Materials and Methods

Thirty-four patients with dysphagia were evaluated. Videofluoroscopic swallowing study was performed for each patient in 90° upright and in 45° reclining sitting posture. Patients swallowed 5 types of boluses twice: sequentially 2 mL thin liquid, 5 mL thin liquid, thick liquid, yogurt, and cooked rice. Data such as the penetration-aspiration scale (PAS), oral transit time (OTT), pharyngeal delay time (PDT), pharyngeal transit time (PTT), residue in valleculae and pyriform sinuses, premature bolus loss, and nasal penetration were obtained.

Results

The mean PAS on the 2 mL thin liquid decreased significantly in the 45° reclining sitting posture (p=0.007). The mean PAS on 5 mL thin liquid in the 45° reclining sitting posture showed decreasing tendency. The residue in valleculae decreased significantly for all boluses in the 45° reclining sitting posture (p<0.001, p=0.002, p=0.003, p<0.001, p=0.020, respectively). The residue in pyriform sinuses increased significantly on 5 mL thin liquid, thick liquid, and yogurt (p=0.031, p=0.020, p=0.002, respectively). There were no significant differences in OTT, PDT, PTT, premature bolus loss, and nasal penetration between both postures.

Conclusion

PAS on 2 mL thin liquid and residue in valleculae on all types of boluses were decreased in a 45° reclining sitting posture. Therefore, we believe that the 45° reclining sitting posture on swallowing is beneficial for the patients with penetration or aspiration on small amounts of thin liquid and large amounts of residue in valleculae.     

Effect of Moderate Hypothermia on the Expression of ICAM-1 in Rat Acute Lung Injury

Clinical and experimental studies have provided that anearly event in the development of acute lung injury (ALI)is the accumulation and activation of neutrophils in thelung. The up regulation of intercellular adhesion moleculesis required fo…     

Effect of Interleukin-1β on Lipid Peroxidation in Emotiogenic Structures of the Brain in Rats during Acute Stress

We studied the effects of immunomodulatory cytokine interleukin-1β on lipid peroxidation in emotiogenic structures of the brain (hypothalamus, sensorimotor cortex, and amygdala) of behaviorally active and passive rats with different prognostic resistance to stress. Immobilization of animals with simultaneous electrocutaneous stimulation (1 h) served as the model of acute emotional stress. Intraperitoneal injection of IL-1β (5 μg/kg) was followed by accumulation of malonic dialdehyde (end-product of lipid peroxidation) in all structures of the brain in passive rats, as well as in the hypothalamus of active animals. As differentiated from active rats, stress exposure in passive specimens was accompanied by a selective increase in malonic dialdehyde content in the sensorimotor cortex and amygdala. Pretreatment with IL-1β prevented activation of lipid peroxidation in the studied structures of the brain in passive rats after stress exposure. Our results show the specifi c effect of IL-1β on free-radical processes in the hypothalamus, sensorimotor cortex, and amygdala in rats with various behavioral parameters. Regional features of lipid peroxidation in emotiogenic structures of the brain in animals with different emotional reactivity probably contribute to the existence of signifi cant variations in the individual resistance to emotional stress.     

Effect of ��2-Adrenergic Receptor Polymorphism in Asthma Control of Patients Receiving Combination Treatment

Purpose

Combination treatment of inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the β2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA.

Materials and Methods

43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 µg/day) plus terbutaline (5 µg prn). as needed. During the 24-week active treatment period, they received budesonide 160 µg and formoterol 4.5 µg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology.

Results

During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV₁) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients.

Conclusion

Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy.     

Effect of Thalidomide on the Expression of TNF-α m-RNA and Synthesis of TNF-α in Cells from Leprosy Patients with Reversal Reaction

Hypersensitivity reactions called reversal reaction (RR) and erythema nodosum leprosum (ENL) occur in leprosy. They are characterized by an increase in tumor necrosis factor-alpha (TNF-α). Thalidomide is an effective treatment for ENL but not RR. Its effectiveness in ENL is attributed to inhibition of TNF-α, and this does not explain its failure to treat RR. We assessed thalidomide's effect on TNF-α in RR. Mononuclear cells from RR and non-RR patients and healthy individuals were treated with thalidomide and M.leprae (AFB), a cytosol fraction of M. leprae or Dharmendra lepromin. Thalidomide suppressed TNF-α, but when some RR patients' cells were stimulated with AFB, it enhanced TNF-α.     

Catheter Ablation of Atrial Fibrillation Raises the Plasma Level of NGF-β Which Is Associated with Sympathetic Nerve Activity

Purpose

The expression of nerve growth factor-β (NGF-β) is related to cardiac nerve sprouting and sympathetic hyper innervation. We investigated the changes of plasma levels of NGF-β and the relationship to follow-up heart rate variability (HRV) after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF).

Materials and Methods

This study included 147 patients with AF (117 men, 55.8±11.5 years, 106 paroxysmal AF) who underwent RFCA. The plasma levels of NGF-β were quantified using double sandwich enzyme linked immunosorbent assay method before (NGF-β_pre) and 1 hour after RFCA (NGF-β_post-1hr). HRV at pre-procedure (HRV_pre), 3 months (HRV_post-3mo), and 1 year post-procedure (HRV_post-1yr) were analyzed and compared with plasma levels of NGF-β.

Results

1) The plasma levels of NGF-β significantly increased after RFCA (20.05±11.09 pg/mL vs. 29.60±19.43 pg/mL, p<0.001). The patients who did not show increased NGF-β_post-1hr were older (p=0.023) and had greater left atrial volume index (p=0.028) than those with increased NGF-β_post-1hr. 2) In patients with NGF-β_pre >18 pg/mL, low frequency components (LF)/high-frequency components (HF) (p=0.003) and the number of atrial premature contractions (APCs, p=0.045) in HRV_post-3mo were significantly higher than those with ≤18 pg/mL. 3) The LF/HF at HRV_post-3mo was linearly associated with the NGF-β_pre (B=4.240, 95% CI 1.114-7.336, p=0.008) and the NGF-β_post-1hr (B=7.617, 95% CI 2.106-13.127, p=0.007). 4) Both NGF-β_pre (OR=1.159, 95% CI 1.045-1.286, p=0.005) and NGF-β_post-1hr (OR=1.098, 95% CI 1.030-1.170, p=0.004) were independent predictors for the increase of LF/HF at HRV_post-3mo.

Conclusion

AF catheter ablation increases plasma level of NGF-β, and high plasma levels of NGF-β_pre was associated with higher sympathetic nerve activity and higher frequency of APCs in HRV_post-3mo.     

Effect of γ-PGA on the formation of collagen fibrils in vitro

The effect of γ-poly(glutamic acid) (γ-PGA) on the self-assembly of collagen was studied. Under physiological conditions, the kinetic curves for fibril formation showed that the turbidity of collagen/γ-PGA blends at 313 nm was increased with the addition of γ-PGA. Furthermore, it was shown using both field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) that fibrils with a larger diameter were obtained following the addition of γ-PGA, probably due to the electrostatic and hydrogen bond interactions between collagen and γ-PGA, which promoted the lateral association of collagen molecules. In addition, both the thermal stability and viscoelastic properties of the hybrid hydrogels, which were evaluated by differential scanning calorimetry and rheological measurements, respectively, were improved by the addition of γ-PGA.     

Ultrastructural Pathology of the Heart in Patients with ß-Thalassaemia Major

Renal AL-amyloidosis is usually lambda-light-chain-related, particularly lambda type 6. Kappa-light-chain-related renal amyloidosis is a rare entity. Relatively few cases have been reported in the literature. The pathologic findings in some of these cases may mimic other disease processes. It is important to recognize the different morphologic expressions of this entity in order to render the right diagnosis. The authors discuss one such case in which the initial pathologic impression was erroneous and, upon further studies, including ultrastructural immunogold labeling, the diagnosis of kappa-light-chain-related renal amyloidosis was established.