Antisocial personality disorder in primary care patients with somatization disorder

Antisocial personality disorder and somatization disorder (SD) have been associated in previous research conducted primarily in patients from the mental health setting. We tested the hypothesis that patients with SD from the primary care setting had less likelihood of having comorbid antisocial personality disorder in a sample of 118 patients with SD. Two methods for diagnosing antisocial personality disorder were used: the Diagnostic Interview Schedule (DIS) and the Structured Clinical Interview for DSM-III-R, axis II (SCID-II). Eight percent of the women and between 18% and 25% (depending on the method used) of the men had antisocial personality, a prevalence rate that clearly exceeds the rate found in the general population. However, in clinical work, only one in 10 women and one in six men with SD will have antisocial personality disorder. These findings are consistent with the shared biological substrate hypothesized for the two disorders.     

Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin.

Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYP1A2) activity in vivo, the 13C-[N-3-methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S-mephenytoin. Breath tests were performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7-day washout period. The mean percentage exhalation of the 13C test dose, as determined by 13CO2 in breath during 8 hours, was 23.0% +/- 8.0% (n = 18) before treatment. The largest increases in exhalation rate of 13CO2 were observed in the poor metabolizers and the intermediate metabolizers (range, 12.8% to 62.9%; median, 38.9%); median area under the plasma concentration-time curves (AUC) of omeprazole was four times higher than in the extensive metabolizers. The change after omeprazole treatment in extensive metabolizers ranged from -9.8% to +47.7% (median, 12.3%; n = 12) of pretreatment values. In both groups exhalation rates of 13CO2 returned to near pretreatment values within the 7-day washout period (24.2% +/- 7.8%; n = 17). Changes in the 13C-caffeine breath test correlated well with both the pretreatment value (R = -0.67, p = 0.003; n = 18) and the plasma AUC of omeprazole (R = 0.61, p = 0.007; n = 18). Therapeutic doses of omeprazole seem to induce CYP1A2 activity in poor metabolizers, whereas they exert minor inducing effects in extensive metabolizers of S-mephenytoin.     

Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression

A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica) is the expression of the virulence (V)-antigen (LcrV). LcrV is a released protein which is involved in contact-induced secretion of yersinia antihost proteins and in evasion of the host's innate immune response. Here we report that recombinant LcrV signals in a CD14- and toll-like receptor 2 (TLR2)-dependent fashion leading to immunosuppression by interleukin 10 induction. The impact of this immunosuppressive effect for yersinia pathogenesis is underlined by the observation that TLR2-deficient mice are less susceptible to oral Y. enterocolitica infection than isogenic wild-type animals. In summary, these data demonstrate a new ligand specificity of TLR2, as LcrV is the first known secreted and nonlipidated virulence-associated protein of a Gram-negative bacterium using TLR2 for cell activation. We conclude that yersiniae might exploit host innate pattern recognition molecules and defense mechanisms to evade the host immune response.     

Unapparent microsporidial infection among immunocompetent humans in the Czech Republic

In the present population-based study, we determined the prevalences of the most common human-pathogenic microsporidia, Encephalitozoon spp. and Enterocytozoon bieneusi, in asymptomatic healthy people living in the Czech Republic. A total of 382 males and females (ages, 1 to 84 years) living in the Czech Republic, of whom 265 were Czech nationals and 117 were foreign students, were included in a study testing for the presence of microsporidia by use of coprology and molecular methods. Single-species infections with Enterocytozoon bieneusi or an Encephalitozoon sp. were detected for 9 and 136 individuals, respectively. Moreover, coinfections were detected for 14 individuals. Four genotypes of 3 human-pathogenic Encephalitozoon spp. and 7 E. bieneusi genotypes, including 3 novel genotypes, were detected. Some of these were reported in humans for the first time. The highest prevalence was recorded for individuals older than 50 years and for loose, unformed stool samples. These findings clearly show that exposure to microsporidia is common among immunocompetent people and that microsporidiosis is not linked to any clinical manifestation in healthy populations.     

Treatment of primary sclerosing cholangitis

Opinion statement Aims of treatment for primary sclerosing cholangitis are as follows: prevention of progression of hepatobiliary disease, reduction of symptoms and consequences of cholestasis (pruritus, osteoporosis), and prevention of complications (colorectal cancer, hepatobiliary cancer). Ursodeoxycholic acid (UDCA) improves biliary secretion and laboratory parameters of cholestasis, but its effects on liver histology and survival are not clear. It reduces the incidence of dysplasias and carcinomas of the colon in patients with colitis and possibly has a beneficial effect on the incidence of bile duct carcinomas. At present, UDCA represents the most promising therapeutic option. Immunosuppressive treatment has not been proven to be effective; it appears to be indicated in the overlap syndrome with autoimmune hepatitis but may be harmful in bacterial cholangitis. Bacterial cholangitis is common in patients with dominant stenoses and requires antibiotic treatment. Endoscopic treatment of dominant stenoses improves cholestasis and prolongs survival in comparison to predicted survival. Pruritus represents a problem in some patients, and cholestyramine represents the first-line treatment. If ineffective, opioid antagonists, rifampin, or ondansetron may be tried. For treatment of osteoporosis and osteopenia, calcium and vitamin D supplementation are recommended, and in selected cases, bisphosphonates may be indicated. In patients with severe cholestasis and coagulation defects, parenteral supplementation of vitamin K may be indicated. During treatment, all patients should be regularly screened for colonic and bile duct carcinomas. Patients with cirrhosis of the liver and its complications are treated accordingly, and in end-stage disease, liver transplantation is indicated.     

Liver-homing of purified glucose oxidase: a novel in vivo model of physiological hepatic oxidative stress (H2O2)

BACKGROUND/AIMS: Reactive oxygen species (ROS), such as H2O2, are implicated in normal and pathological liver function. However, due to the lack of suitable in vivo models of ROS generation the (patho) physiological relevance of H2O2 remains controversial. METHODS: We established a novel model of sustained hepatic H2O2 release using intravenous administration of purified Aspergillus niger glucose oxidase (GOX) in rats. RESULTS: GOX is rapidly cleared from the blood stream and almost exclusively localizes to Kupffer cells. GOX maintained its ability to generate H2O2 over 24h. While sublethal GOX doses induced hepatocellular necrosis, our morphological and functional studies show that lower levels of GOX which generate H2O2 comparable to release by inflammatory cells are non-toxic and do not induce histological inflammation. However, these non-toxic H2O2 levels increased oxidized glutathione and induced heme oxygenase 1 in the liver. In addition, several hepatocyte transporters were downregulated, while no decrease of bile formation, a sensitive marker of liver function, was observed. CONCLUSIONS: Our in vivo model allows to study the effects of extracellular H2O2 in the liver as is released by inflammatory cells. Thus analysis of the role of this major ROS in the absence of confounding inflammatory cofactors will be possible.     

Chemokines and chemokine receptors in the brain: implication in neuroendocrine regulation

Chemokines are small secreted proteins that chemoattract and activate immune and non-immune cells both in vivo and in vitro. In addition to their well-established role in the immune system, several recent reports have suggested that chemokines and their receptors may also play a role in the central nervous system (CNS). The best known central action is their ability to act as immunoinflammatory mediators. Indeed, these proteins regulate leukocyte infiltration in the brain during inflammatory and infectious diseases. However, we and others recently demonstrated that they are expressed not only in neuroinflammatory conditions, but also constitutively by different cell types including neurons in the normal brain, suggesting that they may act as modulators of neuronal functions. The goal of this review is to highlight the role of chemokines in the control of neuroendocrine functions. First, we will focus on the expression of chemokines and their receptors in the CNS, with the main spotlight on the neuronal expression in the hypothalamo-pituitary system. Secondly, we will discuss the role--we can now suspect--of chemokines and their receptors in the regulation of neuroendocrine functions. In conclusion, we propose that chemokines can be added to the well-described neuroendocrine regulatory mechanisms, providing an additional fine modulatory tuning system in physiological conditions.