Effects of early life adversity on immune function and cognitive performance: results from the ALSPAC cohort

Social Psychiatry and Psychiatric Epidemiology - Early life adversity (ELA) is a significant risk factor for mental health disorders. One hypothesised mechanism by which this occurs is via an...     

Dosimetrie an HDR-Afterloading-Geräten mit Ir-192- und Co-60-Strahler: Vergleich verschiedener internationaler Dosimetrieprotokolle

The air kerma rate in air at a reference distance of 1 meter from the source is the recommended quantity for the specification of gamma ray source in brachytherapy. The absorbed dose for the patients is directly proportional to the air kerma rate. Therefore the air kerma rate should be determined before the first use of the source on patients by a medical physicist who is independent from the source manufacturer. The air kerma rate will then be applied in the calculation of the dose delivered to patients.In practice, high dose rate (HDR) Ir-192 afterloading machines are mostly used in brachytherapy treatment. Currently HDR-Co-60 increasingly come into operation, too. The essential advantage of the use of Co-60 sources is its longer half-life compared to Ir-192. In addition, the purchasing and disposal costs are lower. The use of HDR-Co-60- afterloading machines is also quite interesting for developing countries.This work describes the dosimetry at HDR afterloading machines according to the protocols DIN 6809-2 (1993) in relation to the DGMP-Report 13 (2006), IAEA-TECDOC-1274 (2002) and AAPM Report 41 (1993) with the nuclides Ir-192 and Co-60. We have used 3 different measurement methods (with a cylindrical chamber in solid phantom and in free air and with a well chamber) in dependence of each of the protocols.We have shown that the standard deviations of the measured air kerma rate for the Co-60 source are generally larger than those of the Ir-192 source. The measurements with the well chamber had the lowest deviation from the certificate value. In all protocols and methods the deviations stood for both nuclides by a maximum of about 1.2% for Ir-192 and 2.5% for Co-60-sources respectively.     

Different blood acetaldehyde concentration following ethanol administration in a newly developed high alcohol preference and low alcohol preference rat model system

A significant difference in blood-acetaldehyde concentration was observed between high alcohol-preference (HAP) rats and low alcohol-preference (LAP) rats, newly developed different alcohol preference lines. This difference of acetaldehyde accumulation may be due to cytosolic aldehyde dehydrogenase (ALDH1) polymorphism, which has been reported previously. As the doses of ethanol we employed are higher than that of voluntary drinking, there may be little direct relationship between acetaldehyde accumulation and alcohol preference. We suggest therefore that the ALDH1 polymorphism is associated with alcohol preference in HAP/LAP lines through some other unidentified mechanism.     

In vivo electrical activity of brainstem neurons in fetal rats during asphyxia

To see changes in the activity and the sensitivity to glutamate of fetal brain neurons during asphyxia, the electrical activity of brainstem neurons was recorded extracellularly in fetal rats which were still connected with the dams by the intact umbilical cord. In urethan-anesthetized pregnant rats, fetal asphyxia (2–10 min) was induced by occluding the umbilical cord with a surgical clip, while reperfusion of the umbilical blood flow was performed by local application of a relaxant of blood vessels to the occlusion site. The spontaneous discharge of fetal brainstem neurons was suppressed for a long period of time by umbilical cord occlusion. The suppression of the firing occurred 48–150 (78±7) s after the start of umbilical cord occlusion, and lasted even after fetal cortical PO₂ recovered to control level after reperfusion. The changes occurred with a marked reduction in spike amplitude. A similar suppression was observed for the spikes induced by iontophoretic application of glutamate, although fetal brainstem neurons were extremely sensitive to glutamate before asphyxia. The suppression of the spontaneous spikes became more notable and longer when asphyxia was repeated. These findings suggest that the long-lasting suppression of fetal neurons during asphyxia may contribute to a reduction of cellular energy requirements in the fetal brain, thereby playing a role in the resistance of fetal neurons to brain damage caused by asphyxia. Furthermore, the reduced sensitivity of fetal neurons to glutamate during asphyxia may also contribute to prevent brain damage due to excitotoxity of glutamate.     

Gender-specific protective effect of hemoglobin on arsenic-induced skin lesions.

Chronic arsenic poisoning remains a public health crisis in Bangladesh. As arsenic has been shown to bind to human hemoglobin (Hb), hematologic mechanisms may play a role in the pathway through which arsenic exerts its toxicity. Two separate studies, a case-control and a cohort, were conducted to investigate the role of Hb in the development of arsenic-induced skin lesions. In the first, conditional logistic regression was used to investigate the effect of Hb on skin lesions among 900 case-control pairs from Pabna, Bangladesh, in which individuals were matched on gender, age, and location. In the second, mixed linear regression models were used to examine the association between toenail arsenic, urinary arsenic, and Hb within a cohort of 184 individuals from 50 families in the same region who did not have arsenic-induced skin lesions. Hb was significantly associated with skin lesions but this association was gender specific. In males, a 40% reduction in the odds of skin lesions occurred for every 1 g/dL increase in Hb (odds ratio, 0.60; 95% confidence interval, 0.49-0.73). No effect was observed for females (odds ratio, 1.16; 95% confidence interval, 0.92-1.46). In the cohort of 184 individuals, no associations between toenail arsenic or urinary arsenic species and Hb levels were observed. Low Hb levels may exacerbate the detrimental health effects of chronic arsenic poisoning. Whereas providing clean water remains the optimal solution to Bangladesh's problem of arsenic poisoning, improving nutrition and reducing iron-deficiency anemia may ameliorate negative health effects, such as skin lesions in individuals who have been exposed.     

Early-outgrowth bone marrow cells attenuate renal injury and dysfunction via an antioxidant effect in a mouse model of type 2 diabetes

Cell therapy has been extensively investigated in heart disease but less so in the kidney. We considered whether cell therapy also might be useful in diabetic kidney disease. Cognizant of the likely need for autologous cell therapy in humans, we sought to assess the efficacy of donor cells derived from both healthy and diabetic animals. Eight-week-old db/db mice were randomized to receive a single intravenous injection of PBS or 0.5 × 10(6) early-outgrowth cells (EOCs) from db/m or db/db mice. Effects were assessed 4 weeks after cell infusion. Untreated db/db mice developed mesangial matrix expansion and tubular epithelial cell apoptosis in association with increased reactive oxygen species (ROS) and overexpression of thioredoxin interacting protein (TxnIP). Without affecting blood glucose or blood pressure, EOCs not only attenuated mesangial and peritubular matrix expansion, as well as tubular apoptosis, but also diminished ROS and TxnIP overexpression in the kidney of db/db mice. EOCs derived from both diabetic db/db and nondiabetic db/m mice were equally effective in ameliorating kidney injury and oxidative stress. The similarly beneficial effects of cells from healthy and diabetic donors highlight the potential of autologous cell therapy in the related clinical setting.     

A Role for Intestinal Alkaline Phosphatase in the Maintenance of Local Gut Immunity

Background and Aims

Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor known to dephosphorylate lipopolysaccharide (LPS); however, the role of IAP in the gut response to luminal bacteria remains poorly defined. We investigated immune responses of wild-type (WT) and IAP-knockout (IAP-KO) mice to LPS and Salmonella typhimurium challenges.

Methods

Cryostat sectioning and standard indirect immunohistochemical staining for major histocompatibility complex (MHC) class II molecules were performed on liver tissue from WT and IAP-KO mice. WT and IAP-KO mice were orally gavaged with S. typhimurium; bacterial translocation to mesenteric nodes, liver, and spleen was determined by tissue homogenization and plating. In other experiments, WT and IAP-KO mice received intraperitoneal injections of LPS, with subsequent quantification of complete blood counts and serum interleukin (IL)-6 by enzyme-linked immunosorbent assay (ELISA). WT and IAP-KO whole blood were plated and stimulated with LPS and Pam-3-Cys, followed by cytokine assays.

Results

Immunohistologic liver examinations showed increased expression of MHC class II molecules in IAP-KO mice. Following S. typhimurium challenge, WT mice appeared moribund compared with IAP-KO mice, with increased bacterial translocation. WT mice had >50% decrease (P < .005) in platelets and 1.8-fold (P < .05) increased serum IL-6 compared with IAP-KO mice in response to LPS injections. IAP-KO whole-blood stimulation with LPS and Pam-3-Cys resulted in increased IL-6 and tumor necrosis factor (TNF)-alpha secretion compared with WT.

Conclusions

IAP-KO mice exhibit characteristics consistent with local LPS tolerance. Whole-blood response of IAP-KO mice did not reflect systemic tolerance. These data suggest that IAP is a local immunomodulating factor, perhaps regulating LPS?Ctoll-like receptor 4 (TLR4) interaction between commensal microflora and intestinal epithelium.     

Presentation and endoscopic management of biliary ascariasis

Ascaris lumbricoides is a common parasite and the most serious and dramatic presentation is hepatobiliary and pancreatic ascariasis (HPA). Therefore, this study was planned prospectively to elucidate the clinical presentation of HPA and evaluate the efficacy and safety of endoscopic intervention. In this study we documented 77 consecutive patients with HPA from January 2000 to November 2005. All the patients had endoscopically proven HPA. A total of 77 patients were included in the study. The age ranged from 6 to 80 years, with the third decade most commonly (28.6%) affected. Females were 6 times more likely to be affected than males. The commonest presentation was biliary colic (97.4%); other presentations were acute cholangitis (15.6%), obstructive jaundice (9.1%), acute pancreatitis (6.5%), choledocholithiasis (6.5%), acute cholecystitis (6.5%) and liver abscess (2.6%). In this report 51 (66.2%) had living, 10 (13%) had dead and 16 (20.8%) had both living and dead worms. Choledocholithiasis was associated only with dead worms. From one to 23 worms were found in the biliary tree. In 94.8% of cases we had to remove the worm by wide papillotomy followed by basket extraction. We did not experience any major complications during or following the procedures. Three patients had recurrent HPA during the course of follow-up (1 to 12 months). The majority of patients with HPA presented with biliary colic. This should be kept in mind in the management of an acute abdomen, especially in tropical countries. Endoscopic extraction is a safe and effective procedure for the treatment of HPA.     

Lipoprotein status among urban populations in Bangladesh

ObjectiveSerum lipoprotein is the most important predictor for microvascular diseases, and may be influenced by rapid urbanization. Currently available data are limited, particularly regarding age-specific lipoprotein status in urban Bangladeshi populations.MethodsBlood lipoprotein levels of 51,353 male and female individuals primarily residing in urban Bangladesh were analyzed. De-identified data (collected between January 2005 and December 2011) were extracted from the Clinical Biochemistry Laboratory Data Archive of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). For analyses, six age categories were created: (i) <20 years, n = 481; (ii) 20–29 years, n = 1602; (iii) 30–39 years, n = 7272; (iv) 40–49 years, n = 13,582; (v) 50–59 years, n = 15,890; and (vi) 60 years and more, n = 12,526.ResultsMean serum levels of TC, LDL, TG, LDL:HDL and TC:HDL were significantly higher among adults 30–39 years old compared to other age groups, regardless of sex. The proportion of high TC and LDL from 2005 to 2011 among individuals aged 30–39 years old varied widely (p < 0.01 for trend and all pairwise tests).Conclusion30–39 years old individuals had higher concentration of lipoprotein, which increases microvascular disease risk. Further population-based studies are needed to validate our observations in rural areas of Bangladesh.