Coxsackievirus-induced acute neonatal central nervous system disease model

Coxsackievirus B (CVB) is a significant pathogen that causes pediatric central nervous system disease with acute syndromes commonly. The onset of its infection was abrupt, and after recovery there usually will be severe mental sequelae. The disease model for research was not established by the way of natural infection, although there are various investigations about the CVB-induced central nervous system (CNS) diseases. Thus, we have established an acute neonatal CNS disease mice model by CVB orally infecting. This model imitated the natural infection route and focuses the onset of CNS disease, inducing severe infection and lesion in the hippocampus and cortex regions, and the stability of the model was demonstrated. A pathology score system was developed for quantitative pathology analysis, which standardizes the CNS pathology analysis by statistics analysis. By this model, the track of CVB penetrating the blood brain barrier in vivo has been captured. One of the experimental strains CVB3/Macocy, as a new variant, was isolated, and its genomic RNA was cloned. According to its nucleotide sequence, we have characterized its genomic structure and defined its genotype. Based on the sequence, some mutations which do not change the CVB-induced CNS damage have been found. The model is an effective tool for studies on CVB-induced CNS diseases.     

Acute myeloid leukaemia genomics

Acute myeloid leukaemia (AML) is a biologically complex, molecularly and clinically heterogeneous disease. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, standard treatment options have not significantly changed during the past three decades. AML is characterized by multiple somatically acquired mutations that affect genes of different functional categories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone. By contrast, mutations involving NPM1 or signalling molecules (e.g., FLT3, RAS gene family) are typically secondary events that occur later during leukaemogenesis. This review aims to provide an overview of advances in new prognostic markers, including targetable mutations that will probably guide the development and use of novel molecularly targeted therapies.     

Eleutheroside B or E enhances learning and memory in experimentally aged rats

Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer’s disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.     

Adult Hemolytic-Uremic Syndrome Associated with Urosepsis Due to Shigatoxin-Producing Escherichia Coli O138:H-

We report the case of a 62-year-old man without prodromal symptoms who developed a hemolytic-uremic syndrome (HUS) one week after the diagnosis of an acute bacteremic urinary infection (UTI). In this patient, the E. coli isolated in blood cultures was a non-O157:H7 Shigatoxin-producing strain that could subsequently be identified as O138:H-. This is a strain that is normally found in pigs and that has never been isolated in humans previously. UTI-related HUS is a rare event, as until now, only 14 pediatric and 3 adult cases have been reported. Indeed, this new case, besides its interesting microbiological aspects, should heighten our awareness of UTI-related HUS as a rare but real condition, not only in young children but also in adult patients. This should emphasize the necessity to search actively for other sources of Shigatoxin-producing E. coli in patients presenting with HUS without gastrointestinal symptoms.     

Postconditioning Protects Skeletal Muscle Against a Long-Lasting Vascular Occlusion

ABSTRACT

Purpose/Aim of the Study: Long-lasting lower limb arterial occlusion is a condition with high incidence and complication rates. With the absence of appropriate treatment to cure advanced complications, mortality rates are high. Postconditioning (PC) might be capable of limiting the degree of ischemic-reperfusion (IR) injuries, thus reducing complications and mortality rates. The aim of this study was to evaluate the impact of postconditioning during the first postoperative day on skeletal muscle after a long-lasting arterial occlusion. Materials and Methods: Male Wistar rats (n = 72) underwent 8 hr of infrarenal aortic occlusion followed by 2, 6, 12, or 24 hr of reperfusion. In one group of each reperfusion period, postconditioning was applied. Muscle samples were collected for histological examinations. Furthermore, muscle fiber viability and muscle wet-to-dry ratio were assessed. Blood samples were taken for creatine-kinase measurements. Results: Postconditioning strongly reduced morphological injury compared to the corresponding ischemic-reperfusion group (p < .001). Serum creatine-kinase levels showed a peak at 6 hr post-ischemia (IR: 6702.2 ± 797.5; PC: 5523.3 ± 769.3 IU/l) and decreased to normal level by the end of the experiment (Sham: 171.5 ± 71.6; IR: 186.2 ± 82.7; PC: 174.2 ± 72.4 IU/l). Creatine-kinase levels were significantly reduced by postconditioning (p_2hr = .028; p_6hr = .06; p_12hr = .042). A marked decrease in viability was observed in the ischemic-reperfusion groups (2 hr: 11.0 ± 4.1; 6 hr: 10.3 ± 3.6; 12 hr: 9.4 ± 3.3; 24 hr: 8.6 ± 2.8%), whereas with postconditioning, viability was preserved (2 hr: 26.4 ± 5.5; 6 hr: 24.6 ± 4.5; 12 hr: 24.5 ± 6.8; 24 hr: 26.2 ± 6.1%; p < .001); moreover, a significant decrease in the wet-to-dry ratio was achieved (p < .001). Conclusion: Postconditioning was able to reduce local complications after a long-lasting lower limb vascular occlusion.     

Health and Safety Issues Relating to Maine's Fishing Industry

SUMMARY

The Maine Agricultural Safety and Health Program performed a needs assessment to determine the health and safety concerns of Maine's fishing community. Information for the assessment was obtained from clinicians, focus groups of wives of fishers, and government agencies. Reports from the United States Coast Guard showed that during 1993-1994, sixty-five people were injured on commercial fishing vessels and eight people died. Decompression illness was the most frequently reported non-fatal injury (n = 15). Chronic injuries reported by clinicians included back pain, tendinitis, carpal tunnel syndrome, dysbaric osteonecrosis. Clinicians and family members were also concerned about hand and arm infections from the bait and sun exposure. Family health issues and access to care are addressed in the report. Recommendations include, in part, increasing surveillance, reducing barriers to access, increasing clini-cians' knowledge about the fishing industry, and fostering collabora-tion between agencies providing health and safety information to fishers.     

Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent

Context: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse.

Objective: To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure.

Materials and Methods: Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 µg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. Results: DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP.

Conclusions: Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies.