Spectral changes of brain activity in rat offspring exposed to aluminium during gestation and lactation

Exposure to aluminium during gestation causes changes in mammalian brain development and behavior. Our aim was to perform spectral analysis on electrocortical activity of Sprague Dawley male pups (30±3 days of age) whose mothers were treated with aluminium during gestation and lactation. There was a higher presence of power spectra in the delta range of parietal electrocortical activity, a lower presence in the theta range and increased values of the parameter DT as the ratio of delta to theta range in pups indirectly exposed to aluminium (whose mothers were drinking a 0.5% water solution of aluminium chloride during the gestation and lactation periods), compared to controls

Secondary Outcomes of a Pilot Randomized Trial of Azithromycin Treatment for Asthma

OBJECTIVES: The respiratory pathogen Chlamydia pneumoniae (C. pneumoniae) produces acute and chronic lung infections and is associated with asthma. Evidence for effectiveness of antichlamydial antibiotics in asthma is limited. The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice settings where most asthma is encountered and managed. The secondary objectives were to investigate (1) whether azithromycin treatment would affect any asthma outcomes and (2) whether C. pneumoniae serology would be related to outcomes. This report presents the secondary results. DESIGN: Randomized, placebo-controlled, blinded (participants, physicians, study personnel, data analysts), allocation-concealed parallel group clinical trial. SETTING: Community-based health-care settings located in four states and one Canadian province. PARTICIPANTS: Adults with stable, persistent asthma. INTERVENTIONS: Azithromycin (six weekly doses) or identical matching placebo, plus usual community care. OUTCOME MEASURES: Juniper Asthma Quality of Life Questionnaire (Juniper AQLQ), symptom, and medication changes from baseline (pretreatment) to 3 mo posttreatment (follow-up); C. pneumoniae IgG and IgA antibodies at baseline and follow-up. RESULTS: Juniper AQLQ improved by 0.25 (95% confidence interval; −0.3, 0.8) units, overall asthma symptoms improved by 0.68 (0.1, 1.3) units, and rescue inhaler use decreased by 0.59 (−0.5, 1.6) daily administrations in azithromycin-treated compared to placebo-treated participants. Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up (p = 0.04), but IgG was not (p = 0.63). Overall asthma symptom improvement attributable to azithromycin was 28% in high IgA participants versus 12% in low IgA participants (p for interaction = 0.27). CONCLUSIONS: Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms. Larger community-based trials of antichlamydial antibiotics for asthma are warranted

Antimicrobial activity of apple cider vinegar against Escherichia coli, Staphylococcus aureus and Candida albicans; downregulating cytokine and microbial protein expression

The global escalation in antibiotic resistance cases means alternative antimicrobials are essential. The aim of this study was to investigate the antimicrobial capacity of apple cider vinegar (ACV) against E. coli, S. aureus and C. albicans. The minimum dilution of ACV required for growth inhibition varied for each microbial species. For C. albicans, a 1/2 ACV had the strongest effect, S. aureus, a 1/25 dilution ACV was required, whereas for E-coli cultures, a 1/50 ACV dilution was required (p < 0.05). Monocyte co-culture with microbes alongside ACV resulted in dose dependent downregulation of inflammatory cytokines (TNFα, IL-6). Results are expressed as percentage decreases in cytokine secretion comparing ACV treated with non-ACV treated monocytes cultured with E-coli (TNFα, 99.2%; IL-6, 98%), S. aureus (TNFα, 90%; IL-6, 83%) and C. albicans (TNFα, 83.3%; IL-6, 90.1%) respectively. Proteomic analyses of microbes demonstrated that ACV impaired cell integrity, organelles and protein expression. ACV treatment resulted in an absence in expression of DNA starvation protein, citrate synthase, isocitrate and malate dehydrogenases in E-coli; chaperone protein DNak and ftsz in S. aureus and pyruvate kinase, 6-phosphogluconate dehydrogenase, fructose bisphosphate were among the enzymes absent in C.albican cultures. The results demonstrate ACV has multiple antimicrobial potential with clinical therapeutic implications

The Transmembrane Domain of CEACAM1-4S Is a Determinant of Anchorage Independent Growth and Tumorigenicity

CEACAM1 is a multifunctional Ig-like cell adhesion molecule expressed by epithelial cells in many organs. CEACAM1-4L and CEACAM1-4S, two isoforms produced by differential splicing, are predominant in rat liver. Previous work has shown that downregulation of both isoforms occurs in rat hepatocellular carcinomas. Here, we have isolated an anchorage dependent clone, designated 253T-NT that does not express detectable levels of CEACAM1. Stable transfection of 253-NT cells with a wild type CEACAM1-4S expression vector induced an anchorage independent growth in vitro and a tumorigenic phenotype in vivo. These phenotypes were used as quantifiable end points to examine the functionality of the CEACAM1-4S transmembrane domain. Examination of the CEACAM1 transmembrane domain showed N-terminal GXXXG dimerization sequences and C-terminal tyrosine residues shown in related studies to stabilize transmembrane domain helix-helix interactions. To examine the effects of transmembrane domain mutations, 253-NT cells were transfected with transmembrane domain mutants carrying glycine to leucine or tyrosine to valine substitutions. Results showed that mutation of transmembrane tyrosine residues greatly enhanced growth in vitro and in vivo. Mutation of transmembrane dimerization motifs, in contrast, significantly reduced anchorage independent growth and tumorigenicity. 253-NT cells expressing CEACAM1-4S with both glycine to leucine and tyrosine to valine mutations displayed the growth-enhanced phenotype of tyrosine mutants. The dramatic effect of transmembrane domain mutations constitutes strong evidence that the transmembrane domain is an important determinant of CEACAM1-4S functionality and most likely by other proteins with transmembrane domains containing dimerization sequences and/or C-terminal tyrosine residues

Models of Traumatic Cerebellar Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Studies of human TBI demonstrate that the cerebellum is sometimes affected even when the initial mechanical insult is directed to the cerebral cortex. Some of the components of TBI, including ataxia, postural instability, tremor, impairments in balance and fine motor skills, and even cognitive deficits, may be attributed in part to cerebellar damage. Animal models of TBI have begun to explore the vulnerability of the cerebellum. In this paper, we review the clinical presentation, pathogenesis, and putative mechanisms underlying cerebellar damage with an emphasis on experimental models that have been used to further elucidate this poorly understood but important aspect of TBI. Animal models of indirect (supratentorial) trauma to the cerebellum, including fluid percussion, controlled cortical impact, weight drop impact acceleration, and rotational acceleration injuries, are considered. In addition, we describe models that produce direct trauma to the cerebellum as well as those that reproduce specific components of TBI including axotomy, stab injury, in vitro stretch injury, and excitotoxicity. Overall, these models reveal robust characteristics of cerebellar damage including regionally specific Purkinje cell injury or loss, activation of glia in a distinct spatial pattern, and traumatic axonal injury. Further research is needed to better understand the mechanisms underlying the pathogenesis of cerebellar trauma, and the experimental models discussed here offer an important first step toward achieving that objective

Haplotype and AGG Interspersion Analysis of FMR1 Alleles in a Croatian Population: No Founder Effect Detected in Patients with Fragile X Syndrome

Several studies have suggested that fragileXsyndrome (FRAXA), the most common inherited form of mental retardation, originated from a limited number of founder chromosomes. The aim of this study is to assess the genetic origin of fragile X syndrome in a Croatian population. We performed a haplotype analysis of the polymorphic loci DXS548 and FRAXAC1 in 18 unrelated fragile X and 56 control chromosomes. The AGG interspersion pattern of the FMR1 CGG repeat region was analyzed by sequencing. This is the first report on haplotype and AGG interspersion analysis of the fragile X syndrome gene in a Croatian population—the only eastern European population of Slavic origin analyzed so far. Our findings are intriguing, because they show a distinct distribution of the DXS548 and FRAXAC1 alleles in our fragile X population compared to other European fragile X populations. The DXS548/FRAXAC1 haplotype 194/154 (7-3), which is common among normal populations, was found to be the most frequent haplotype in our fragile X population as well. The AGG interspersion analysis indicated that AGG loss rather than haplotype may determine FMR1 allele instability. Our results suggest that no common ancestral X chromosome is associated with fragile X syndrome in the Croatian population studied. Further analysis of the origin of fragile X syndrome among other Slavic populations will be necessary to better define its eastern European distribution