Metabolic Studies,Aldosterone Secretion Rate,and Plasma Renin after Carbenoxolone Sodium

A formal metabolic study of carbenoxolone sodium (Biogastrone) 300 mg./day has been performed for 17 days on a woman with gastric ulcer who in a previous 21-day trial, on a 52-mEq sodium diet, showed weight gain, retention, and rise in plasma sodium and chloride concentrations, as well as hypokalaemia without change in potassium balance. In the present trial sodium intake was restricted to 26 mEq/day; while plasma electrolyte changes of lesser degree still occurred, there was no retention of water, sodium, or chloride. Aldosterone secretion in the control period was 202 μg./24 hours, and fell to 74 μg./24 hours after carbenoxolone, but plasma renin was unchanged.These results suggest that the mineralocorticoid effects of carbenoxolone (and presumably of liquorice and its other derivatives) are due to an intrinsic aldosterone-like action, and that, with sodium deprivation, aldosterone secretion is suppressed by a mechanism which is not renin-mediated—possibly hypokalaemia.     

Plasma 11-Hydroxycorticosteroid and Growth Hormone Levels in Acute Medical Illnesses

Adrenal cortical response in acute medical illness has been studied by measuring the plasma 11-hydroxycorticosteroid (11-OHCS) concentration in 178 patients. Those with unbalanced diabetes, acute infections, and severe myocardial infarction had high levels. The results obtained suggest that in a patient with a severe infection and hypotension a plasma 11-OHCS level of less than 15 μg./100 ml. indicates an inadequate adrenal cortical response, and one patient with septicaemia and temporary adrenal cortical insufficiency is described. Growth hormone levels were increased in patients with severe diabetic ketosis but not in those with hyperosmolar non-ketotic diabetic coma.     

Pectin-Based Bioadhesive Delivery of Carbenoxolone Sodium for Aphthous Ulcers in Oral Cavity

The objective of this study was to prepare and evaluate the pectin-based dosage form for buccal adhesion. Carbenoxolone sodium, which is used for the treatment of aphthous ulcers in oral cavity, was used as a model drug. The pectin buccal discs were prepared by direct compression. The water uptake and erosion of pectin disc increased progressively with the swelling time. The bioadhesion of dried pectin discs decreased when either the discs were hydrated or the buccal tissue was wet with a small volume of medium. The influencing factors such as pectin type, pectin to lactose ratio, and sweetener type on the formulations were investigated. The results demonstrated that buccal discs prepared from pectin with a high degree of esterification (DE) showed a weaker and more friable characteristic than that with low DE. Decreasing pectin to lactose ratio resulted in the high dissolution rate with low bioadhesive properties. Addition of sweetener in the formulations also affected the hardness, friability, and bioadhesive properties of the discs. The pectin discs containing sweetening agent showed a higher drug release than those without sweetener. The results suggested that pectin-based bioadhesive discs could be used to deliver carbenoxolone sodium in oral cavity.     

Elevated Plasma Angiopoietin-2 Levels and Primary Graft Dysfunction after Lung Transplantation

Introduction

Primary graft dysfunction (PGD) is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.

Methods

We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE).

Results

There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40%) and 47 non-PGD subjects (59%) received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF). Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03). The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02); there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD) (p = 0.9).

Conclusions

Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.     

Relation of Plasma Homocysteine to Plasma Amyloid Beta Levels

Background Elevated plasma homocysteine and amyloid β (Aβ) have been associated with Alzheimer’s disease (AD). We investigated the cross-sectional association between these biomarkers. Methods We used linear regression to relate plasma homocysteine and Aβ adjusting for age, gender, creatinine, APOE-ε4, and ethnic group in 327 persons aged 78 ± 6.6 years. Results Plasma homocysteine correlated with age, serum creatinine, plasma Aβ40 and Aβ42, and was inversely correlated with serum vitamin B12, and folate. Aβ42, but not Aβ40, was related to later development of dementia. Homocysteine was related to higher Aβ40 levels (coefficient = 2.0; P < 0.0001) and this association was attenuated after adjustment for creatinine (coefficient = 1.0; P < 0.0001). The crude association between homocysteine and Aβ42 was weaker (coefficient = 0.5; P = 0.01) and became non-significant after adjustment for creatinine (coefficient = 0.4; P = 0.06). These associations were unrelated to ethnicity, the presence of APOE-ε4 or dementia. Analyses by quartiles of homocysteine showed that these association were driven primarily by the fourth quartile. Conclusions Plasma homocysteine is directly related to Aβ40. The association with Aβ42 is not significant. These results seem to indicate that homocysteine is related to aging but not specifically to AD. Special issue dedicated to John P. Blass.     

Double-blind Trial of Carbenoxolone Sodium Capsules in Duodenal Ulcer Therapy,Based on Endoscopic Diagnosis and Follow-up

A high-dose double-blind trial of carbenoxolone sodium capsules (Duogastrone) in the treatment of duodenal ulceration was combined with endoscopic diagnosis and follow-up. Thirty-one ambulant patients with an endoscopically visible duodenal ulcer were allocated at random to a 12-week course of treatment with either carbenoxolone sodium 300 mg daily or a placebo. Symptomatic and endoscopic follow-up was performed at 2-4 weeks, 6-8 weeks, and 12-16 weeks. Carbenoxolone was shown to increase the rate of healing of duodenal ulcers in the early stages of treatment, but by 12 weeks there was no difference between the two groups. There was no significant difference in symptomatic improvement between the two groups at any stage of treatment. Side effects, especially hypokalaemia, were prominent in the patients treated with carbenoxolone. There was a poor relation between endoscopic and symptomatic improvement in patients on either form of treatment.     

Plasma Corticosteroid Levels in Laying Hens

Corticosteroids were measured in blood samples collected from 10 hens in two series with a time interval of nine days. In the first series blood was collected by venipuncture (wing vein), in the second by cardiac puncture. In each series, sampling took place immediately before (control), and 5 min as well as 18 h after intentional rough handling. Only samples obtained by cardiac puncture 5 min after rough handling showed markedly elevated hormone levels. Corticosteroids were also measured in blood collected from two other groups of hens, each including 10 birds. Samples were taken at 0 (control), 1, 5 and 40 min, one group being sampled by venipuncture, the other by cardiac puncture, None of the groups were subjected to rough handling. The hormone levels in samples obtained were significantly higher (P < 0.005) than the levels in the corresponding samples obtained by venipuncture.     

Benzodiazepines and Tricyclic Antidepressant Plasma Levels

Twelve patients acted successfully as subjects to study what effect if any the benzodiazepines nitrazepam, diazepam, oxazepam, and chlordiazepoxide might have on steady-state plasma levels of nortriptyline and amitriptyline. No significant detectable effect was discovered. In view of the known interaction effects of other alternative tranquillizing drugs and hypnotics it seems reasonable to choose benzodiazepines wherever possible when anxiolytics or hypnotics need to be added during treatment of depression with tricyclic antidepressants.     

Changes of Body Weight and Plasma Ghrelin Levels after Gastric Banding and Gastric Bypass

Objective: Ghrelin is an enteric peptide with strong orexigenic and adipogenic effects. Plasma ghrelin levels are decreased in obese subjects but increase after weight loss; this increase is not observed after Roux‐en‐Y gastric bypass (RYGB). Prospective and comparative data after adjustable silicone gastric banding (ASGB) have not been reported previously. Research Methods and Procedures: Overnight fasting plasma ghrelin concentration was measured in morbidly obese subjects at baseline and 3, 6, 12, and 24 months after ASGB (n = 8) or RYGB (n = 5) and in nonoperated controls (n = 7). Results: After RYGB, body weight (BW) decreased by 29.5 ± 5.5 kg (mean ± SE, p < 0.001), whereas plasma ghrelin failed to increase significantly (+167 ± 119 pg/mL, not significant). In contrast, after ASGB, BW decreased less (by 22.8 ± 5.9 kg; p < 0.001), and plasma ghrelin significantly increased by 377 ± 201 pg/mL (p = 0.025). Neither BW nor plasma ghrelin changed in nonoperated controls. Plasma leptin decreased in both operated groups (similarly p < 0.05) but not in nonoperated controls. Plasma growth hormone and insulin‐like growth factor 1 were not correlated with changes in plasma ghrelin concentrations. Discussion: Plasma ghrelin levels failed to increase during substantial weight loss after RYGB, but did increase in response to lesser weight loss after ASGB. These findings suggest that the plasma ghrelin response after weight loss is impaired after exclusion of major parts of the stomach and the duodenum (RYGB), and the smaller long‐term weight loss after ASGB compared with RYGB may be due, at least in part, to an absent increase in plasma ghrelin after RYGB.     

Changes of Plasma B-Type Natriuretic Peptide Levels after High-Pressure Post-Dilation following Coronary Stent Deployment

Objective

To evaluate the changes of plasma B-type natriuretic peptide(BNP) levels after high-pressure post-dilation following coronary stent deployment.

Methods

A total of 173 patients undergoing percutaneous coronary intervention for the left anterior descending artery were enrolled into the study. All patients were divided into two groups: the conventional group and the post-dilation group. The plasma BNP, troponin I(TnI), myocardial band isoenzyme of creatine kinase(CK-MB) levels and the serum high sensitive C-reactive protein(hs-CRP) levels immediately before and 24 hours after the interventional procedures were compared between the two groups.

Results

There were no significant differences between the two groups in terms of clinical features, clinical and biochemical parameters, stent parameters, pre-procedural plasma BNP and TnI levels, pre-procedural serum hs-CRP levels, as well as pre- and post-procedural CK-MB levels (all P>0.05). In the conventional group, post-procedural plasma BNP levels were significantly reduced when compared with the pre-procedural levels, median(25th,75th) were 32.5 ng/L(15.0,52.4) vs. 37.7 ng/L(18.2,67.3), P = 0.001. In the post-dilation group, post-procedural plasma BNP levels were significantly increased when compared with the pre-procedural levels, median(25th,75th) were 53.5 ng/L(29.6,82.8) vs. 44.2 ng/L(17.15,70.7), P<0.0001. Post-procedural plasma TnI levels were also significantly increased when compared with the pre-procedural levels in both groups, median(25th,75th) were 0.02 ng/L(0.01,0.08) vs. 0.01 ng/L(0.01,0.01), 0.05 ng/L(0.01,0.35) vs. 0.01 ng/L(0.01,0.01), respectively, P<0.0001, so were the serum hs-CRP levels, median(25th,75th) were 3.3 mg/L(2.4,4.7) vs. 2.2 mg/L(1.4,3.3), 4.2 mg/L(3.175,5.825) vs. 2.3 mg/L(1.45,3.6), respectively, P<0.0001. Post-procedural plasma BNP, TnI and serum hs-CRP levels in the post-dilation group were significantly higher than those in the conventional group(all P<0.0001).

Conclusion

High-pressure post-dilation following coronary stent deployment resulted in a significant increase of plasma BNP levels, as well as plasma TnI levels and serum hs-CRP levels, which may be related to myocardial perfusion, more myocardial injury and more inflammation.     

甘珀酸对大鼠大脑中动脉缺血再灌注后星形胶质细胞增殖及活化的影响

目的探讨缝隙连接阻断剂甘珀酸对大鼠大脑中动脉(Middle Cerebral Artery,MCA)缺血再灌注模型半暗带区星形胶质细胞增殖及活化的影响。方法成年雄性SD大鼠80只,随机分为生理盐水组(n=35)、CBX干预组(n=35)和假手术组(n=10)。CBX干预组术前1h右侧侧脑室注射CBX,生理盐水组右侧侧脑室注射生理盐水,建立标准大脑中动脉梗死模型,缺血1h后再灌注6h、1d、3d、7d,免疫荧光及免疫印迹的方法观察GFAP,Ki67,PCNA的表达情况。结果与对照组比较,CBX干预组大鼠术后半暗带区GFAP的表达量减少,Ki67与GFAP双阳性细胞减少(P0.05),PCNA的表达量没有明显的变化。结论甘珀酸可以抑制缺血引起的星形胶质细胞的活化增殖。     

Altered Levels of Acetylcholinesterase in Alzheimer Plasma

Background

Many studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE) in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem.

Principal Findings

Here we have estimated the levels of AChE activity in human plasma by first immunoprecipitating BuChE and measuring AChE activity in the immunodepleted plasma. Human plasma AChE activity levels were ∼20 nmol/min/mL, about 160 times lower than BuChE. The majority of AChE species are the light G₁+G₂ forms and not G₄ tetramers. The levels and pattern of the molecular forms are similar to that observed in individuals with silent BuChE. We have also compared plasma AChE with the enzyme pattern obtained from human liver, red blood cells, cerebrospinal fluid (CSF) and brain, by sedimentation analysis, Western blotting and lectin-binding analysis. Finally, a selective increase of AChE activity was detected in plasma from Alzheimer''s disease (AD) patients compared to age and gender-matched controls. This increase correlates with an increase in the G₁+G₂ forms, the subset of AChE species which are increased in Alzheimer''s brain. Western blot analysis demonstrated that a 78 kDa immunoreactive AChE protein band was also increased in Alzheimer''s plasma, attributed in part to AChE-T subunits common in brain and CSF.

Conclusion

Plasma AChE might have potential as an indicator of disease progress and prognosis in AD and warrants further investigation.     

Inheritance of Plasma Cholesterol Levels in Mice

Mean plasma cholesterol levels were determined at two ages in mice from eight unrelated inbred strains (BALB/cJ, BDP/J, CBA/J, C57BL/6J, LP/J, RF/J, SJL/J, and 129/J). Significant strain, sex, and age differences were observed. Estimates of the degree of genetic determination of the trait obtained from an analysis of the strain data averaged 58 +/- 4% for the males and 54 +/- 8% for the females.-Selection for high and low plasma cholesterol levels produced two significantly different and distinct lines. Selection was initiated in a genetically heterogeneous population derived from an eight-way cross of the inbred strains listed above. After five generations of selection the divergence of the high and low lines amounted to 4 phenotypic standard deviations of the foundation population. Realized heritability estimated from the regression of divergence on the combined cumulative selection differential was 51 +/- 5% for the males and 50 +/- 3% for the females. The results indicate that genetic factors are important in controlling plasma cholesterol levels in the mouse and that the majority of these factors act additively.     

Association between Reduction of Plasma Adiponectin Levels and Risk of Bacterial Infection after Gastric Cancer Surgery

Background and Purpose

Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities.

Methods

We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ² test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility.

Results

Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively.

Conclusion

T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection.