Propofol suppresses macrophage functions and modulates mitochondrial membrane potential and cellular adenosine triphosphate synthesis

BACKGROUND: Propofol is an intravenous anesthetic agent that may impair host defense system. The aim of this study was to evaluate the effects of propofol on macrophage functions and its possible mechanism. METHODS: Mouse macrophage-like Raw 264.7 cells were exposed to propofol, at 3, 30 (a clinically relevant concentration), and 300 microm. Cell viability, lactate dehydrogenase, and cell cycle were analyzed to determine the cellular toxicity of propofol to macrophages. After administration of propofol, chemotactic, phagocytic, and oxidative ability and interferon-gamma mRNA production were carried out to validate the potential effects of propofol on macrophage functions. Mitochondrial membrane potential and cellular adenosine triphosphate levels were also analyzed to evaluate the role of mitochondria in propofol-induced macrophage dysfunction. RESULTS: Exposure of macrophages to 3 and 30 microm propofol did not affect cell viability. When the administered concentration reached 300 microm, propofol would increase lactate dehydrogenase release, cause arrest of cell cycle in G1/S phase, and lead to cell death. In the 1-h-treated macrophages, propofol significantly reduced macrophage functions of chemotactic and oxidative ability in a concentration-dependent manner. However, the suppressive effects were partially or completely reversed after 6 and 24 h. Propofol could reduce phagocytic activities of macrophages in concentration- and time-dependent manners. Exposure of macrophages to lipopolysaccharide induced the mRNA of interferon-gamma, but the induction was significantly blocked by propofol. Propofol concentration-dependently decreased the membrane potential of macrophage mitochondria, but the effects were descended with time. The levels of cellular adenosine triphosphate in macrophages were also reduced by propofol. CONCLUSIONS: A clinically relevant concentration of propofol can suppress macrophage functions, possibly through inhibiting their mitochondrial membrane potential and adenosine triphosphate synthesis instead of direct cellular toxicity.     

Acute changes in plasma non-esterified fatty acid concentration do not change hepatic glucose production in people with type 2 diabetes

The effect of changes in plasma non-esterified fatty acid concentration (NEFA) on plasma glucose concentration, hepatic glucose production (Ra), and glucose disposal (Rd) rates was determined in 14 patients with Type 2 diabetes. Seven patients had relatively mild fasting hyperglycaemia (less than 10.0 mmol l-1), whereas the remaining seven had relatively severe fasting hyperglycaemia (greater than 14.0 mmol l-1). Each patient was infused from 2000 to 0800 h with 3-3H-glucose on two occasions, with or without neutral fat emulsion and heparin (mild hyperglycaemia group), or with or without nicotinic acid (severe hyperglycaemia group). Plasma NEFA concentration increased from 0.33 +/- 0.06 (+/- SE) to 4.78 +/- 0.42 mmol l-1 in response to the lipid and heparin infusion, but plasma glucose concentration (7.8 +/- 0.7 vs 7.4 +/- 0.8 mmol l-1), Ra (0.44 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1), and Rd (0.42 +/- 0.02 vs 0.46 +/- 0.02 mmol m-2 min-1) were unchanged. Nicotinic acid decreased plasma NEFA concentration from 0.54 +/- 0.15 to 0.23 +/- 0.08 mmol l-1, but plasma glucose (15.0 +/- 1.0 vs 15.5 +/- 1.4 mmol l-1), Ra (0.74 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1), and Rd (0.73 +/- 0.07 vs 0.68 +/- 0.07 mmol m-2 min-1) were unchanged. The results indicate that acute changes in plasma NEFA concentration did not lead to any change in overnight glucose production or disposal rates.     

Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction

Serum hepatitis B virus (HBV) DNA was assayed using polymerase chain reaction, in 107 HBsAg-negative normal Chinese subjects. The results showed that eight subjects (7.5%) had HBV DNA. In the subgroup with antibody to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), 7.3% (5/68) were positive for HBV DNA; HBV DNA was not detected in six individuals with anti-HBs only and in nine with anti-HBc only. In four persons with anti-HBc and anti-HBe, one had HBV DNA. In 20 subjects negative for all hepatitis B serological markers, two (10%) were found to have HBV DNA. This study indicates that serological markers are not adequate to rule out HBV infection, and it further implies that present blood donor screening methods may need improving.     

Detection of hepatitis B viral DNA by polymerase chain reaction in patients with hepatitis B surface antigen

Hepatitis B virus (HBV) DNA was assayed using the polymerase chain reaction in serum samples of 116 hepatitis B surface antigen (HBsAg) carriers, including 30 positive for hepatitis B e antigen (HBeAg) and 86 negative for HBeAg. In the HBeAg-positive group, all were positive for HBV DNA. In the HBeAg-negative group, 80.2% were positive for HBV DNA (80.0% in the healthy carrier group, 90.0% in the chronic active liver disease group, and 69.2% in patients with cirrhosis). This study indicated that every HBeAg-positive carrier as well as the majority of HBeAg-negative carriers were infectious and, in the latter group, that viral replication is most active in patients with chronic active liver disease.     

Detection ofHelicobacter pylori in gastric biopsy tissue by polymerase chain reaction

To evaluate the sensitivity of a polymerase chain reaction (PCR) assay using nested primers in detectingHelicobacter pylori, gastric tissue biopsy specimens were collected on endoscopy from 17 patients with a duodenal ulcer. DNA was extracted by phenol/chloroform treatment or boiling in water, and then subjected to a nested PCR using two primer pairs from the urease gene ofHelicobacter pylori. Fourteen of the 17 patients were positive forHelicobacter pylori using DNA samples extracted by either method. The PCR results correlated well with the results of an enzyme immunoassay to detect IgG antibody. However, there were two culture negative patients. The three PCR negative patients were both culture negative and serologically negative. DNA from 9 of the 14 patients was randomly selected and subjected to semiquantification by serial dilutions, and then PCR. The results showed that phenol/chloroform extraction yielded 10–1000 times more DNA than the boiling method. It is concluded that the PCR assay is a rapid and sensitive method for detectingHelicobacter pylori, and that phenol/chloroform extraction is superior to simple boiling in obtaining DNA samples for PCR.     

Immunohistological analysis of stress-induced phosphoprotein 1 in ovarian cancer patients with low serum cancer antigen 125 levels

ObjectiveStress-induced phosphoprotein 1 (STIP1) was recently identified as a potential tumor marker for human ovarian cancer. This study further evaluates the usefulness of STIP1 in ovarian tumor patients with normal CA125 serum levels.Materials and MethodsSTIP1 and CA125 were immunohistochemically analyzed in 84 primary ovarian cancer and 30 benign ovarian tumors in patients with serum CA125 levels < 35 U/mL before surgery. Histoscores (0–300) were calculated as staining intensities (0–3) multiplied by percentage of tumor tissue (0–100%).ResultsThe cell types of the 84 cancers included 11 serous, 10 clear-cell, 51 mucinous, and 12 endometrioid carcinomas. There were 55 patients with invasive cancer and 29 with borderline ovarian tumors. The histoscores of STIP1, but not of CA125, in invasive cancer (mean ± SD, 186.3 ± 82.5) were significantly (p < 0.0001) higher than those seen in borderline ovarian tumors (86.2 ± 85.5). When the STIP1 histoscore was set at 183.8, invasive cancers (n = 55) were identified from benign tumors (n = 30) with a sensitivity of 56.4%, a specificity of 93.3%, a positive predictive value of 93.9%, and a negative predictive value of 53.8%. Results of receiver operating characteristics analysis showed that the area under curve of the STIP1 histoscore was 0.755, which was superior to that of CA125 (0.599).ConclusionSTIP1 histoscores may be useful in detecting invasive human ovarian cancer in patients with low serum CA125 levels.     

Supplementation of Los Angeles classification with esophageal mucosa index of hemoglobin can predict the treatment response of erosive reflux esophagitis

Background  

We assessed whether the esophageal mucosa index of hemoglobin (IHb) could assist the Los Angeles (LA) classification in defining the severity of erosive reflux esophagitis (RE) and predicting the treatment response by esomeprazole.     

46,XY gonadal dysgenesis associated with congenital nephrotic syndrome and sepsis

The occurrence of nephrosis in the first 3 months of life is rare and is termed ’congenital nephrotic syndrome.’ The congenital nephrotic syndrome is a group of heterogeneous diseases with a clinical course that differs markedly from the childhood nephrotic syndrome. The coexistence of a congenital nephrotic syndrome and gonadal dysgenesis in a 46,XY karyotype with normal female external genitalia is extremely rare. Frequent severe infections are often seen in the Finnish type, but sepsis leading to death is rare in the neonatal onset of gonadal dysgenesis. This report describes an unusual case of complete XY gonadal dysgenesis in a 46,XY female neonate with the congenital nephrotic syndrome and overwhelming sepsis. Received: 4 January 1999 / Revised: 24 May 1999 / Accepted: 25 May 1999     

Interleukin‐18 gene 105A/C genetic polymorphism is associated with the susceptibility of Kawasaki disease

Interleukin‐18 (IL‐18)‐656T/G, ‐607A/C, and ‐137C/G promoter polymorphisms had been reported associated with Kawasaki disease (KD). An IL‐18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma, rheumatoid, and systemic lupus erythematosus. We tested a hypothesis that the IL‐18 105A/C genetic polymorphism confers KD susceptibility. Study participants were Taiwanese KD patients and a healthy control group. Our data indicated that the frequency of C allele was significantly higher in the patient group (13.9%) than in the control group (2.7%; P<0.0001, odds ratio [OR]=5.93; 95% confidence interval [CI]=2.57–13.73). Therefore, persons with the C allele may have higher risk of deve loping KD. In addition, compared with the haplotype frequencies between case and control groups, the KD patients with TACC haplotype appeared to be a significant “at‐risk” haplotype compared with other haplotypes (OR: 4.62, 95% CI: 1.71–12.43; P=0.001). KD patient with the TAGA haplotype appeared to be a significant “protective” haplotype compared with other haplotypes (OR: 0.51, 95% CI:0.29–0.89; P=0.017). Our results suggest that 105A/C polymorphism and the haplotypes in IL‐18 gene are associated with the risk of KD in Taiwanese population. Clin. Lab. Anal. 23:71–76, 2009. © 2009 Wiley‐Liss, Inc.