Induction and metal speciation of metallothionein in wood mice (Apodemus sylvaticus) along a metal pollution gradient

We investigated the binding of Cd, Cu, and Zn to metallothionein (MT) and other metal-binding proteins in free-living wood mice (Apodemus sylvaticus L.) captured in four areas along a metal pollution gradient. We measured total and cytosolic Cd, Cu, and Zn concentrations in mouse liver and kidney by means of inductively coupled plasma-mass spectrometry (ICP-MS). Total (Cu, Cd, Zn)-MT levels were determined in the same tissues by means of the cadmium thiomolybdate saturation assay. Metal speciation of metalloproteins was studied by means of size-exclusion high-performance liquid chromatography-ICP-MS. Liver and kidney of wood mice from the site adjacent to the pollution source showed the highest Cd and Zn concentrations (total and cytosolic) and (Cu, Cd, Zn)-MT levels compared to the other sites farther away from the pollution source. No or only small site differences in tissue Cu concentrations were observed. Almost all the variation (85-95%) in hepatic and renal (Cu, Cd, Zn)-MT levels was explained by the total or cytosolic hepatic Zn and Cd concentration or the renal Cd concentration, respectively. An analysis of the cytosolic metal speciation showed that the Cd-MT, Cu-MT, and Zn-MT fractions in liver and kidney increased significantly with increasing cytosolic metal concentrations. Metals associated with the other cytosolic protein fractions did not increase with increasing exposure. These results illustrate the important role of MT in metal homeostasis and detoxification processes. We conclude that MT is a useful biomarker for environmental metal contamination in free-living wood mice.     

Painful conditions in the Achilles tendon region: a common problem in middle-aged competitive badminton players

Overuse injuries are the most frequent type in badminton, generally localized in the legs. An earlier study found 32% of young Swedish elite badminton players to have experienced disabling pain in the Achilles tendon region during the previous 5 years. The present investigation examined the prevalence and characteristics of painful conditions in the Achilles tendon region in 32 middle-aged competitive badminton players by means of questionnaire and physiotherapist's examination. Pain in the Achilles tendon region was reported by 44%, either presently or during the past 5 years, generally localized in the middle portion of the tendon. Symptoms had lasted 2 weeks-1 year (96 days). On the competition days 22% of the reported pain currently in the region. Age was found to be correlated to Achilles tendon pain, but there was no relationship between symptoms of pain and body mass index, gender, training quantity, or years of playing badminton. In conclusion, Achilles tendon pain seems to be relatively common among Swedish middle-aged competitive badminton players, particularly in the older ones.     

Fatal acute intestinal pseudoobstruction in mice.

Here we describe the epizootiology and pathology of spontaneous, fatal acute intestinal pseudoobstruction that occurred in a mouse colony of 1000 breeding pairs, mainly of the C57Bl/6 strain and free from known pathogenic agents. Most of the mice affected were dams in the second week of lactation. At necropsy, segments of the small intestines were distended with fluid contents. Widespread apoptosis of the villus epithelium of the small intestine and superficial epithelial cells of the large intestine, associated with strong expression of active caspase 3, was a distinctive feature. Necrotic enterocytes, mucosal erosions, and acute mucosal inflammation were prominent in some mice, and morphologic signs of toxemia were generally present. No light microscopic neuronal changes were apparent in the gut, and no etiologic agents were identified. These results indicate that sudden activation of apoptosis in the trophically stimulated gut epithelium during peak lactation was instrumental for the fatal outcome of the condition, but the primary cause of the motility dysfunction of the bowel was not established.     

Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study

Objective Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients.Design A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries.Interventions None.Patients Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period.Methods Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia.Results We enrolled 97 patients, mean age 64±15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5±4.0. Mean IAP was 9.8±4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance.Conclusion Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.     

Cross-competition of CD8+ T cells shapes the immunodominance hierarchy during boost vaccination

CD8+ T cell responses directed against multiple pathogen-derived epitopes are characterized by defined immunodominance hierarchy patterns. A possible explanation for this phenomenon is that CD8+ T cells of different specificities compete for access to epitopes on antigen-presenting cells, and that the outcome of this so-called cross-competition reflects the number of induced T cells. In our study using a vaccinia virus infection model, we found that T cell cross-competition is highly relevant during boost vaccination, thereby shaping the immunodominance hierarchy in the recall. We demonstrate that competition was of no importance during priming and was unaffected by the applied route of immunization. It strongly depended on the timing of viral antigen expression in infected APCs, and it was characterized by poor proliferation of T cells recognizing epitopes derived from late viral proteins. To our knowledge, this is the first demonstration of the functional importance of T cell cross-competition during a viral infection. Our findings provide a basis for novel strategies for how boost vaccination to defined antigens can be selectively improved. They give important new insights into the design of more efficient poxviral vectors for immunotherapy.     

Neuroglucopenia and Metabolic Distress in Two Patients with Viral Meningoencephalitis: A Microdialysis Study

Background

Cerebral edema is a major cause of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Arginine vasopressin (AVP) and water channel aquaporin-4 (AQP4) have been implicated in the pathogenesis of CA-evoked cerebral edema. In this study, we examined if conivaptan, a V_1a and V₂ antagonist, attenuates cerebral edema following CA/CPR in wild type (WT) mice as well as mice with targeted disruption of the gene encoding α-syntrophin (α-syn^?/?) that demonstrate diminished perivascular AQP4 pool.

Methods

Isoflurane-anesthetized adult male WT C57Bl/6 and α-syn^?/? mice were subjected to 8 min CA/CPR and treated with either bolus IV injection (0.15 or 0.3 mg/kg) followed by continuous infusion of conivaptan (0.15 mg/kg/day or 0.3 mg/kg/day), or vehicle infusion for 48 h. Serum osmolality, regional brain water content, and blood–brain barrier (BBB) disruption were determined at the end of the experiment. Sham-operated mice in both strains served as controls.

Results

Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. In WT mice, conivaptan at 0.3 mg dose significantly attenuated regional water content in the caudoputamen (81.0 ± 0.5 vs 82.5 ± 0.4 % in controls; mean ± SEM) and cortex (78.8 ± 0.2 vs 79.4 ± 0.2 % in controls), while conivaptan at 0.15 mg was not effective. In α-syn^?/? mice, conivaptan at 0.3 mg dose did not attenuate water content compared with controls. Conivaptan (0.3 mg/kg/day) attenuated post-CA BBB disruption at 48 h in WT mice but not in α-syn^?/? mice.

Conclusions

Continuous IV infusion of conivaptan attenuates cerebral edema and BBB disruption following CA. These effects of conivaptan that are dependent on the presence of perivascular pool of AQP4 appear be mediated via its dual effect on V₁ and V₂ receptors.

     

Ethnic disparities: control of glycemia, blood pressure, and LDL cholesterol among US adults with type 2 diabetes

OBJECTIVE: To examine ethnic disparities in the quality of diabetes care among adults with diabetes in the US through a systematic qualitative review. DATA SOURCES: Material published in the English language was searched from 1993 through June 2003 using PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, the Cochrane Library, Combined Health Information Database, and Education Resources Information Center. STUDY SELECTION AND DATA EXTRACTION: Studies of patients with diabetes in which at least 50% of study participants were ethnic minorities and studies that made ethnic group comparisons were eligible. Research on individuals having prediabetes, those <18 years of age, or women with gestational diabetes were excluded. Reviewers used a reproducible search strategy. A standardized abstraction and grading of articles for publication source and content were used. Data on glycemia, blood pressure, and low-density lipoprotein cholesterol (LDL-C) were extracted in patients with diabetes. A total of 390 studies were reviewed, with 78 meeting inclusion criteria. DATA SYNTHESIS: Ethnic minorities had poorer outcomes of care than non-Hispanic whites. These disparities were most pronounced for glycemic control and least evident for LDL-C control. Most studies showed blood pressure to be poorly controlled among ethnic minorities. CONCLUSIONS: Control of risk factors for diabetes (glycemia, blood pressure, LDL-C) is challenging and requires routine assessment. These findings indicate that additional efforts are needed to promote diabetes quality of care among minority populations.