Ischemic but not reperfusion arrhythmias depend upon serum potassium concentration.

The effects of variations in serum concentrations of potassium on the occurrence and severity of ischemia- and reperfusion-induced arrhythmias have been studied in conscious rats. Serum potassium concentrations were modified by maintaining rats on diets which varied in potassium concentration, by treatment with hydrochlorothiazide, amiloride, spironolactone or infusions of potassium chloride. An inverse linear relationship was demonstrated between ischemia-induced arrhythmias and log(e) serum potassium concentration such that a 50% reduction in arrhythmias occur with a 3.8-fold increase in serum potassium concentration. On the other hand, the incidence of reperfusion-induced arrhythmias after 7 min of regional ischemia prior to reperfusion in previously untreated rats were not influenced by elevation of serum potassium concentrations prior to and after reperfusion. Effects on ischemia-induced arrhythmias could not be explained by changes in blood pressure or heart rate. It is speculated that modification of potassium concentration in non-ischemic or border zone ventricular tissue may directly modify arrhythmogenesis due to ischemia but not that due to reperfusion.     

替比夫定对慢性乙型肝炎患者血清和外周血单个核细胞HBV DNA含量及IL-18水平的影响

目的:探讨替比夫定对慢性乙型肝炎(CHB)患者血清和外周血单个核细胞(PBMC)培养上清液中HBV DNA含量及白细胞介素-18(IL-18)水平的影响。方法:检测替比夫定治疗前后CHB轻、中、重度三组患者血清和PBMC HBV DNA含量及IL-18的水平,并同健康对照组做比较。结果:CHB各组患者血清及PBMC培养上清液中IL-18水平同健康对照组相比差异有显著性意义(P0.05),由高到低依次为:重度组、中度组、轻度组;患者血清IL-18水平与血清ALT/AST水平呈显著正相关;替比夫定治疗可以迅速降低病毒负荷,但PBMC内病毒负荷的下降要晚于血清HBV DNA水平的下降;PBMC中IL-18的下降要明显早于血清中IL-18的下降。结论:血清IL-18水平可以作为监测肝细胞炎性损伤程度的一个可靠指标;PBMC上清液中IL-18的水平可以作为一个灵敏的指标早期预测替比夫定抗病毒治疗的效果;PBMC内病毒池的持续存在可能是HBV抗病毒治疗失败的原因之一。     

Substance P-induced increase in vascular permeability in the rat trachea does not depend on neutrophils or other components of circulating blood

An intravascular injection of substance P is known to increase vascular permeability in the rat trachea. Electrical stimulation of the cervical vagus nerve produces a similar response, presumably by releasing substance P or other tachykinins from sensory nerve endings. In the present study, we sought to determine whether the increase in vascular permeability induced by intravascular substance P or by vagal stimulation requires the presence of neutrophils or other components of circulating blood. To eliminate circulating blood, we perfused into the aorta of anesthetized rats an oxygenated Krebs-Henseleit solution containing albumin and monastral blue, a colloidal pigment that does not cross normal tracheal blood vessels. We then injected substance P intravascularly or electrically stimulated the right cervical vagus nerve. Increases in vascular permeability were quantified by using a microspectophotometer to measure the amount of extravasated monastral blue in tracheal whole-mounts. We found that the elimination of neutrophils and other components of circulating blood did not prevent the increase in tracheal vascular permeability induced by intravascular substance P or by vagal stimulation.     

Fenofibrate administration does not affect muscle triglyceride concentration or insulin sensitivity in humans

Animal data suggest that males, in particular, rely on peroxisome proliferator activated receptor-α activity to maintain normal muscle triglyceride metabolism. We sought to examine whether this was also true in men vs women and its relationship to insulin sensitivity (Si). Normolipidemic obese men (n = 9) and women (n = 9) underwent an assessment of Si (intravenous glucose tolerance test) and intramuscular triglyceride (IMTG) metabolism (gas chromatography/mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry from plasma and muscle biopsies taken after infusion of [U-¹³C]palmitate) before and after 12 weeks of fenofibrate treatment. Women were more insulin sensitive (Si: 5.2 ± 0.7 vs 2.4 ± 0.4 ×10⁻⁴/ μU/mL, W vs M, P < .01) at baseline despite similar IMTG concentration (41.9 ± 15.5 vs 30.8 ± 5.1 μg/mg dry weight, W vs M, P = .43) and IMTG fractional synthesis rate (FSR) (0.27%/h ± 0.07%/h vs 0.35%/h ± 0.06%/h, W vs M, P = .41) as men. Fenofibrate enhanced FSR in men (0.35 ± 0.06 to 0.54 ± 0.06, P = .05), with no such change seen in women (0.27 ± 0.07 to 0.32 ± 0.13, P = .73) and no change in IMTG concentration in either group (23.0 ± 3.9 in M, P = .26 vs baseline; 36.3 ± 12.0 in W, P = .79 vs baseline). Insulin sensitivity was unaffected by fenofibrate (P ≥ .68). Lower percentage saturation of IMTG in women vs men before (29.1% ± 2.3% vs 35.2% ± 1.7%, P = .06) and after (27.3% ± 2.8% vs 35.1% ± 1.9%, P = .04) fenofibrate most closely related to their greater Si (R² = 0.34, P = .10) and was largely unchanged by the drug. Peroxisome proliferator activated receptor-α agonist therapy had little effect on IMTG metabolism in men or women. Intramuscular triglyceride saturation, rather than IMTG concentration or FSR, most closely (but not significantly) related to Si and was unchanged by fenofibrate administration.     

Endogenous erythroid colony formation in myeloproliferative diseases does not depend on T cells

We investigated the influence of T-cell depletion on BFU-E and CFU-GM colony growth in vitro from normal individuals and patients with chronic granulocytic leukemia (CGL), idiopathic myelofibrosis (MF), and polycythemia vera (PV). Preincubation of mononuclear cells with the complement-fixing monoclonal antibody OKT11A, which is cytotoxic to T-lymphocytes, significantly reduced the number of erythropoietin (epo)-dependent BFU-E colonies cultured from normal bone marrow and normal peripheral blood, as well as from the blood of patients with CGL, PV, and MF. In contrast, the numbers of epo-independent ("endogenous") BFU-E colonies cultured from the blood of PV and MF patients were the same before and after T-cell depletion. The blood and marrow of CGL patients and normal individuals produced no epo-independent BFU-E proliferation. The growth of day-7 and day-14 CFU-GM was not significantly influenced by T-cell depletion in the majority of experiments. We conclude that T cells promote the growth of epo-dependent BFU-E colonies in vitro, but they do not influence the growth of "endogenous" BFU-E colonies from patients with myeloproliferative disorders.     

Liver cell apoptosis in chronic hepatitis C correlates with histological but not biochemical activity or serum HCV-RNA levels

In hepatitis C virus (HCV) infection, mechanisms responsible for liver cell damage are still poorly understood and both necrosis and apoptosis may be operative. By using terminal deoxynucleotydil transferase-mediated d-UTP-biotin nick-end labeling (TUNEL) we have evaluated and quantified apoptosis in liver biopsy specimens from 61 patients with chronic hepatitis C. All patients had detectable apoptotic cells in the liver. Presence of increased apoptotic activity was confirmed in selected cases by electron microscopy and by DNA gel electrophoresis. The amount of liver cell apoptosis expressed as apoptotic index, ranged between 0.01% to 0.54% and showed a positive correlation with histological activity grading (P <.0005) and with the amount of infiltrating CD8-positive cells (P =. 01). Apoptosis did not correlate with transaminase levels or with HCV load and genotype. These results support the concept that immune-mediated apoptosis may play a role in the pathogenesis of chronic hepatitis C and indicate that this type of reaction may occur in the absence of significant alanine transaminase (ALT) elevation, thus explaining the lack of correlation between biochemical activity and liver histological damage.     

Deficiency of haematopoietic-cell-derived IL-10 does not exacerbate high-fat-diet-induced inflammation or insulin resistance in mice

Aims/hypothesis  

Recent work has identified the important roles of M1 pro-inflammatory and M2 anti-inflammatory macrophages in the regulation of insulin sensitivity. Specifically, increased numbers of M2 macrophages and a decrease in M1 macrophages within the adipose tissue are associated with a state of enhanced insulin sensitivity. IL-10 is an anti-inflammatory cytokine and is a critical effector molecule of M2 macrophages.     

Interleukin-18 does not modulate the acute-phase response

IL-18 is a pro-inflammatory cytokine of the IL-1 family and it induces IL-1, TNF, and IL-6, all of which are endogenous pyrogens. The pyrogenic properties of recombinant IL-18 were studied in a rabbit model of fever. rIL-18 did not cause fever when injected intravenously into rabbits. Furthermore, the ability of rIL-18 to modulate other components of the acute-phase response was assessed. rIL-18 did not induce leukocytosis, or changes of circulating concentrations of lipoproteins and corticosterone in mice. In conclusion, rIL-18 is not able to induce a febrile response in rabbits and does not modulate the acute-phase response in mice.     

慢性乙型肝炎患者血清和外周血单个核细胞IL-18水平与HBV感染的关系

目的 初步探讨慢性乙型肝炎(CHB)患者血清和外周血单个核细胞(PBMC)白细胞介素-18(IL-18)水平与乙型肝炎病毒(HBV)感染的关系.方法 ELISA法检测HBV感染者(轻、中、重度三组)和正常组的血清与PBMC IL-18水平,同时检测血清AJJT/AST水平;荧光定量PCR检测各组患者血清和PBMC HBV DNA量,并分成HBV DNA病毒载量低、中、高三组.结果 CHB各组患者间血清和PBMC培养上清IL-18水平有显著差异(P＜0.05),由高到低依次为:重度组、中度组、轻度组;血清IL-18水平较对照组明显升高(P＜0.05),PBMC培养上清IL-18水平明显低于对照组(P＜0.05);不同血清病毒载量组,血清IL-18水平有显著差异(P＜0.05):由高到低依次为:低病毒载量组、中病毒载量组、高病毒载量组;PBMC内HBV DNA阴性组IL-18水平明显高于HBV DNA阳性组(P＜0.05);CHB患者血清IL-18水平与血清ALT/AST呈显著正相关.结论 IL-18可能参与了CHB的免疫应答,在清除HBV感染同时也造成了肝细胞炎性损伤,其与肝细胞损伤严重程度有一定的相关性.     

Prevention of AIDS dementia by HAART does not depend on cerebrospinal fluid drug penetrance

The impact of the cerebrospinal fluid (CSF) penetrance properties of different highly active antiretroviral therapy (HAART) regimes on cognitive processing in AIDS dementia is still undetermined. We therefore designed a retrospective cross-sectional and prospective longitudinal analysis of event-related potentials in HIV-infected patients with different combinations of HAART or without antiretroviral treatment. A total of 353 consecutive patients without secondary CNS manifestation of HIV infection were enrolled in the cross-sectional study and 135 consecutive patients without secondary CNS manifestations of HIV infection were enrolled in the longitudinal study. HAART in different combinations (n = 306) or no antiretroviral treatment (n = 47) was given for at least 6 months in the retrospective cross-sectional study. HAART in different combinations (n = 110) or no antiretroviral treatment (n = 25) was given for 1 year in the prospective longitudinal study. We evaluated the latency and amplitude of the P3 component of visually evoked event-related potentials and mean choice reaction time as measures of cognitive processing. Patients receiving HAART had decreased P3 latencies as compared to those patients not receiving HAART but P3 latency and P3 amplitude were not correlated with the amount of CSF penetrance of the different HAART combinations in either statistical analysis. However, mean choice reaction time was significantly correlated with the amount of CSF penetrance. In HIV-infected patients, the CSF penetrance properties of HAART do not have any significant influence on cognitive processing as measured by event-related potentials.     

Cardiac catheterization dye does not affect serum thyroid hormone concentrations or tsh secretion

The iodinated contrast agents used in oral cholecystography impair peripheral iodo-thyronine-5′-deiodinase activity, resulting in a transient decrease in serum 3,5,3′-triio-dothyronine (triiodothyronine, T₃) and in increases in serum 3,3′,5′-triiodothyronine (reverse T₃ rT₃) and thyroxine (T₄) concentrations. A related iodinated contrast agent, diatrizoate, is employed in coronary angiography. The effect of diatrizoate (Renografin-76®) on serum T₄, rT₃, and thyroid stimulating hormone (thyrotropin, TSH) concentrations and the TSH and T₃, responses to thyrotropin releasing hormone (TRH) were evaluated in seven euthyroid patients before and on the fifth day following coronary angiography. No significant changes were observed. Thus, diatrizoate, in contrast to the oral cholecystographic agents, appears to have little or no clinically important effect on thyroid hormone metabolism in man.     

IL-18 serum level and IL-18 promoter gene polymorphism in Iranian patients with gastrointestinal cancers

Background and Aim:  Interleukin (IL)-18 level and association of its two promoter gene polymorphisms at −607C/A and −137G/C positions were investigated in Iranian patients with gastrointestinal (GI) cancers.
Methods:  232 cases of GI cancers and 312 healthy controls were enrolled. Serum level of IL-18 was measured by enzyme linked immunosorbent assay (ELISA) and genotyping of IL-18 gene polymorphisms were assessed by allele-specific polymerase chain reaction (PCR).
Results:  There was a significant difference in the frequency of −137 G/C genotype between patients with stomach or colorectal cancers and control group. In patients with colorectal cancer, the frequency of the −607AA/−137GC genotype combination in unwell-differentiated cases was more than those with well-differentiated cancer. Haplotype analysis showed that in patients with stomach cancer −607C/−137C and −607A/−137G and in patients with colorectal cancer −607C/−137C were decreased compared with control group, and this difference reached statistical significance. Serum analysis revealed that the mean IL-18 serum level in stomach and colorectal cancer before and after surgical operation was significantly higher than healthy volunteers. Postoperative IL-18 level for all patients with colorectal cancer was significantly decreased compared with the levels before surgery.
Conclusion:  Results of this investigation suggests that Single Nucleotide Polymorphism (SNP) at position −137 G/C and haplotype frequency may play a role in predisposition of Iranian patients to stomach and colorectal cancers. In addition, increasing serum IL-18 level may have clinical importance as a diagnostic marker in patients with stomach and colorectal cancer.