Abrupt emergence of diverse species B adenoviruses at US military recruit training centers

BACKGROUND: Adenoviruses (Ads) cause continuous outbreaks of acute respiratory disease (ARD) in US military training facilities. In 1996, the loss of vaccines targeting the dominant recruit-associated serotypes precipitated the reemergence of Ads in these populations. Between 1999 and 2002, serotype 4 accounted for >95% of Ads isolated from recruits and for >50% of ARD cases in training facilities (15,000 cases/year). METHODS: Ads (n=1867) collected between 2002 and 2006 from recruits with ARD at 8 military training facilities in the United States were serotyped by serum neutralization and polymerase chain reaction. RESULTS: The dominance of Ad4 continued through 2005, followed by a simultaneous emergence of diverse species B serotypes at the majority of sites. This included the subspecies B1 serotypes 3, 7, and 21 and the subspecies B2 serotype 14. Ad14 was the most prevalent species B serotype, appearing in high numbers at 3 sites and becoming dominant at 1. CONCLUSIONS: Subspecies B2 Ads have rarely been associated with ARD, and only in Eurasia. This survey represents the first report of AdB2-associated ARD in the Western Hemisphere. The simultaneous emergence of several species B Ads suggests a common external source (the civilian population) and a decrease in preexisting immunity to species B Ads.     

Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate

BACKGROUND: In some settings, the response to pentavalent antimonial therapy for leishmaniasis may be lower in children than in adults. We hypothesized that there are age-dependent pharmacokinetic differences of potential clinical relevance. METHODS: We compared the pharmacokinetics of antimony (Sb) in adults and 2 groups of children 3-6 years old who had cutaneous leishmaniasis treated with intramuscular meglumine antimoniate. Adults (n=9) and the first group of children (n=9) received 20 mg Sb/kg/day for 20 days; the second group of children (n=6) received 20 mg Sb/kg for 19 days and 30 mg Sb/kg on day 20. Drug exposure was assessed by the area under the 24-h time-concentration curve (AUC(0-24)) in plasma. RESULTS: Children (vs. adults) who received 20 mg/kg had a 42% lower AUC(0-24) (mean +/- SE, 111+/-7 vs. 190+/-10 mg x h/L, compared with adults; P<.001), a 16% lower peak concentration (32.7+/-0.9 vs. 38.8+/-2.1 mg/L; P=.04), and a 75% higher weight-adjusted clearance (0.185+/-0.013 vs. 0.106+/-0.006 L/h/kg; P<.001). The 30 mg/kg dose in children increased the AUC(0-24) to 164+/-10 mg x h/L and the peak concentration to 43.8+/-2.3 mg/L. CONCLUSIONS: Drug exposure is significantly lower in children than in adults treated with the same weight-adjusted regimen of meglumine antimoniate, which primarily stems from a higher antimony clearance rate.     

Deflazacort induced stronger immunosuppression than expected

Prednisone (PDN) impairs cognitive functioning and brain structures in humans and animals. Deflazacort (DFZ) is a synthetic glucocorticoid claimed to have lesser side effects than prednisone. The objective of this study was to assess whether chronic administration (90 days) of DFZ produces less neuronal degeneration and glial reactivity than PDN. Male Swiss-Wistar rats were studied. Controls received 0.1 ml distilled water orally. The PDN group received prednisone 5 mg per kg per day orally, and the DFZ group received deflazacort 6 mg per kg per day orally. This model had to be assembled in three different occasions due to excess mortality in the DFZ group. A fourth model was assembled using only the DFZ group and slides of water and PDN-exposed rats from a previous study were used as comparators. The index of degenerated neurons and the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex, CA1, and CA3 hippocampus. The results show that the overall mortality was 49% in the DFZ group, 4.5% in the PDN group, and none of the controls died. Routine necropsy showed infection in multiple organs. The PDN group had two times higher neuronal degeneration in the prefrontal cortex, almost 11 times in CA1, and four times in CA3 hippocampus when compared with controls and DFZ group. Astrocytes reactivity was increased in the PDN- and DFZ-exposed rats compared with controls. The DFZ group showed an average of four times less microgial cells in the three studied regions when compared with controls and the PDN group. In conclusion, it seems that DFZ at the equivalent licensed dose produced a stronger immunosuppressive effect—systemic and in brain tissue—than PDN, but induced less neuronal damage. The immunesuppressant magnitude of DFZ should be further studied in clinical settings.     

Chemotactic effect of melatonin on leukocytes

Melatonin seems to be an important stimulatory factor of the immune system. This indolamine is capable of inducing activation of leukocytes. Tissue leukocyte infiltration is a key feature of inflammatory and immune responses; however, there is no information about the effect of melatonin on leukocyte chemotaxis. Therefore, the aim of this study was to examine the in vitro and in vivo effects of melatonin on leukocyte chemotaxis, on modulation of leukocyte chemotaxis to other chemoattractants and on the in vivo induction of leukocyte chemokines. Neutrophils and mononuclear leukocytes (PBMC) were isolated by a discontinuous gradient on Hystopaque. Chemotaxis was performed in blind well Boyden's chambers. In vivo chemotaxis was determined after intraperitoneal injection of melatonin into rats. Leukocyte chemotactic response and leukocyte chemokine expression were determined in human volunteers treated with 20 mg daily of melatonin. Increased neutrophils and PBMC chemotaxis in response to 1.2 nm melatonin was observed in vitro. Peritoneal leukocytes were found increased after melatonin injection. Humans treated with melatonin showed an increased neutrophil chemotactic response to a physiological chemoattractant and increased expression of intracellular chemokines; however, decreased chemotactic response and no chemokine expression were observed in PBMC. These data suggest that melatonin could have a relevant role during the tissue leukocyte infiltration in inflammatory and immune responses.     

Long-term morphological changes in a cryopreserved pulmonary valve homograft

Pulmonary homografts (PHs) are frequently used to replace the native pulmonary valve in the Ross procedure, and in the reconstruction of the right ventricular outflow tract. The case of a 25-year-old man whose PH was replaced 12 years after undergoing the Ross procedure is reported. The clinical cause of the PH failure was stenosis. Morphological studies showed cusp tissue degeneration with tears and calcification, as well as pannus growth on the flow and nonflow surfaces of the cusps and the pulmonary artery graft. The durability of this PH was likely due to a combination of low pressure on the right side of the heart and the patient's age at surgery.     

Central blockade of IL-1 does not impair taste-LPS associative learning

After saccharin intake is associated with the consequences of peripheral lipopolysaccharide (LPS) administration, rats develop a strong conditioned avoidance behavior against this gustatory stimulus. To investigate the role of central interleukin-1 (IL-1) as a key signal during taste-LPS engram formation, rats were chronically infused with IL-1 receptor antagonist into the lateral ventricle of the brain before, during and after a single association trial. The results indicate that a stable taste-LPS engram can be formed even under the chronic blockade of central IL-1 signaling during engram formation and consolidation. More importantly, our data show that animals which did not experience a fever response during association phase (due to the LPS encounter) were unable to elicit hyperthermia as part of the conditioned response. These data indicate that pairing a relevant taste stimulus with an immune challenge, such as LPS, might result in the formation of multiple engrams, specifically codifying independent information.     

Schizophrenia: From brain morphology to psychopathology

Ten years ago, Velakoulis, the author of a study cited in the present article, was appreciating that the role of functional imaging in schizophrenia research would involve collaboration of clinicians, imaging specialists, and neuropsychologists, and the past year’s literature proves his point. Our review shows that structural and functional imaging in schizophrenia is still alive and well. In the past year, it has focused on changes in “at-risk” and first-episode schizophrenia populations and has been used by researchers to characterize phenotypes of patients with schizophrenia prior to including them in genetic research. A decade ago, O’Donovan and Owen were cautiously optimistic about future advances in finding susceptibility genes for schizophrenia, and this year’s literature, including their review, proves that the massive efforts of research in the genetics of schizophrenia have started to pay off. An almost-obscure area 10 years ago, pharmacogenetics of schizophrenia is well represented in the past year and gives hope to the practicing clinicians who are eagerly waiting to understand patients’ variability in antipsychotic drug response. These and additional areas are included in our review of schizophrenia literature in the past year.     

Advanced glycation end products, oxidative stress and metalloproteinases are altered in the cerebral microvasculature during aging

Biological aging is associated with an increased incidence of cerebrovascular disease. Recent findings indicate that oxidative stress promoting age-related changes of cerebral circulation are involved in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease. The aim of this study was to evaluate the contribution of cerebral microvessels to the oxidative stress during brain aging, by: (i) assessment of precursors for advanced glycation end products (AGE) formation, (ii) activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione disulfide reductase (GR), and (iii) the activities of metalloproteinases (MMPs), MMP-2 and MMP-9, involved in synaptogenesis and memory consolidation. The experiments were performed on two groups of male Wistar rats: 15 young (3-6 months old) and 15 aged (18-24 months old) animals. The cerebral microvessels were isolated by mechanical homogenization, the concentration of protein carbonyls and the activity of antioxidant enzymes were evaluated by spectrophotometry, and gelatin SDS-PAGE zymography was employed to evaluate MMP-2 and MMP-9 activities. The results showed that, by comparison with young rats, aged brain microvessels contain: (i) approximately 106 % increase of protein carbonyls production; (ii) approximately 68% higher GPx activity, unmodified activities of SOD and GR; (iii) approximately 30% diminishment in MMP-2 activity, and the specific occurrence of MMP-9 enzyme. The data suggest that the age-related changes of microvessels could increase the propensity for cerebral diseases and might represent, at least in part, a prerequisite for the deterioration of mental and physical status in the elderly.     

Exercise training on disease control and quality of life in asthmatic children

PURPOSE: Aerobic training has been shown to be effective in improving cardiopulmonary fitness in asthmatic children. However, the actual impact of physical training on clinical indicators of disease control remains controversial. METHODS: Thirty-eight children with moderate to severe persistent asthma were randomly assigned to control (N=17) and training (N=21) groups. Spirometry, exercise challenge, and maximum incremental cardiopulmonary exercise tests were performed 16 wk apart. Daily doses of inhaled steroids and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores were also recorded. RESULTS: Physical training was associated with significant improvements in physiological variables at peak and submaximal exercise (P<0.05); in contrast, no significant changes were found in controls. Severity of exercise-induced bronchoconstriction (EIB) and postexercise breathlessness were significantly lessened in trained patients; improvement in fitness and EIB, however, were not linearly related (P>0.05). In addition, PAQLQ scores improved only in trained children (P<0.01). Daily doses of inhaled steroids were reduced in trained patients (52%), but they remained unchanged or increased in controls (70.6%) (P=0.07). CONCLUSION: Supervised exercise training might be associated with beneficial effects on disease control and quality of life in asthmatic children. These data suggest an adjunct role of physical conditioning on clinical management of patients with more advanced disease.