Adaptation of diverse lyme disease spirochetes in a natural rodent reservoir host

We compared the relative reservoir competence of European wood mice for two genospecies of Lyme disease spirochetes by analyzing susceptibility, intrinsic incubation period, and degree and duration of infectivity. Borrelia afzelii, specializing in particular reservoir hosts, is better adapted to those hosts than is the more generalist genospecies B. burgdorferi sensu stricto.     

Psychosocial group prevention and intervention programs for children and adolescents

Psychosocial group interventions provide a potent venue for promoting children's social competencies, self-regulation, and problem solving in a natural peer group context. Three exemplary prevention and intervention group programs were described that are empirically supported, theoretically rich, and flexible for application in residential care settings. Special considerations are offered for designing and implementing groups with this population.     

Community competence in cardiopulmonary resuscitation

The aim of this study was to determine community application of cardiopulmonary resuscitation (CPR) skills in an emergency, and, thus, assess the value of training programmes in raising community competence. A cross-sectional telephone survey of the Western Australian population was chosen randomly (n = 803). An urban sub-sample (n = 100) performed a practical demonstration of CPR skills using a simulated collapse scenario using a recording manikin as the victim. Performance was assessed by two observers using pre-determined criteria. Of all respondents, 64% had been trained in CPR. Practical and theoretical assessment scores were significantly better in trained versus untrained participants. The number of times a person was trained in CPR was more effective for retention and competence than time since last trained. Degree of training and theoretical competence were less in those aged over 65 years or with heart disease in the household. Theoretical competence poorly reflected practical performance in many tasks. This study provides a comprehensive database of CPR training and performance, and highlights future directions to ensure appropriate and cost-effective training. Specific factors to be addressed include increasing frequency of training, targeting of high-risk groups, simplification in teaching, and emphasising early activation of the emergency medical system.     

Fruit extract of the medicinal plant Crataegus oxyacantha exerts genotoxic and mutagenic effects in cultured cells

Crataegus oxyacantha, a plant of the Rosaceae family also known “English hawthorn, haw, maybush, or whitethorn,” has long been used for medicinal purposes such as digestive disorders, hyperlipidemia, dyspnea, inducing diuresis, and preventing kidney stones. However, the predominant use of this plant has been to treat cardiovascular disorders. Due to a lack of studies on the genotoxicity of C. oxyacantha, this investigation was undertaken to determine whether its fruit extract exerts cytotoxic, genotoxic, or clastogenic/aneugenic effects in leukocytes and HepG2 (liver hepatocellular carcinoma) cultured human cells, or mutagenic effects in TA100 and TA98 strains of Salmonella typhimurium bacterium. Genotoxicity analysis showed that the extract produced no marked genotoxic effects at concentrations of 2.5 or 5 µg/ml in either cell type; however, at concentrations of 10 µg/ml or higher significant DNA damage was detected. The micronucleus test also demonstrated that concentrations of 10 µg/ml or higher produced clastogenic/aneugenic responses. In the Ames test, the extract induced mutagenic effects in TA98 strain of S. typhimurium with metabolic activation at all tested concentrations (2.5 to 500 µg/ml). Data indicate that, under certain experimental conditions, the fruit extract of C. oxyacantha exerts genotoxic and clastogenic/aneugenic effects in cultured human cells, and with metabolism mutagenicity occurs in bacteria cells.     

Increased sphingosine 1‐phosphate mediates inflammation and fibrosis in tubular injury in diabetic nephropathy

Hyperglycemia induces all isoforms of transforming growth factor β (TGFβ), which in turn play key roles in inflammation and fibrosis that characterize diabetic nephropathy. Sphingosine 1‐phosphate (S1P) is a signaling sphingolipid, derived from sphingosine by the action of sphingosine kinase (SK). S1P mediates many biological processes, which mimic TGFβ signaling. To determine the role of SK1 and S1P in inducing fibrosis and inflammation, and the interaction with TGFβ‐1, 2 and 3 signalling in diabetic nephropathy, human proximal tubular cells (HK2 cells) were exposed to normal (5 mmol/L) or high (30 mmol/L) glucose or TGFβ‐1, ‐2, ‐3 ± an SK inhibitor (SKI‐II) or SK1 siRNA. Control and diabetic wild type (WT) and SK1^?/? mice were studied. Fibrotic and inflammatory markers, and relevant downstream signalling pathways were assessed. SK1 mRNA and protein expression was increased in HK2 cells exposed to high glucose or TGFβ1,‐2,‐3. All TGFβ isoforms induced fibronectin, collagen IV and macrophage chemoattractant protein 1 (MCP1), which were reversed by both SKI‐II and SK1 siRNA. Exposure to S1P increased phospho‐p44/42 expression, AP‐1 binding and NFkB phosphorylation. WT diabetic mice exhibited increased renal cortical S1P, fibronectin, collagen IV and MCP1 mRNA and protein expression compared to SK1^?/? diabetic mice. In summary, this study demonstrates that inhibiting the formation of S1P reduces tubulointerstitial renal inflammation and fibrosis in diabetic nephropathy.     

Soy protein with or without isoflavones failed to preserve bone density in gonadal hormone–deficient male rat model of osteoporosis

Soy with its isoflavones has been shown to positively influence bone mineral density in female ovariectomized rats; hence, we hypothesized a similar effect in orchidectomized (ORX) male rats. Forty male Sprague-Dawley rats, aged 95 days, were divided into 4 groups and were either sham operated (Sham) or ORX. The ORX groups were fed a soy protein–based diet (SOY), an isoflavone-depleted soy protein diet (SOY?), or a casein based diet for 65 days after surgery. Orchidectomy increased the rate of bone turnover, resulting in reduced bone mineral density and bone mineral content by 3.5% and 14%, respectively, and compromised biomechanical properties. The mean femoral length of ORX animals was also significantly shorter than Sham animals, but ORX rats that were fed SOY diet did not experience this reduction in bone length, implicating a role for soy protein in bone growth (4.02 ± 0.02, 3.93 ± 0.01, 3.99 ± 0.02, 3.91 ± 0.01 for Sham, ORX, SOY, SOY?, respectively). The SOY and SOY? positively influenced the biomechanical properties of bone such as yield and ultimate force, the measures of bone elasticity, and plasticity. In terms of bone histomorphometry, the data indicate that SOY? tends to reduce ORX-induced increase in bone turnover as evidenced by suppressed bone formation rate/mineralized surface by about 9%. Overall, our results indicated that soy protein, regardless of its isoflavone content, was unable to prevent the ORX-induced femoral decrease in bone density and mineral content. However, soy may enhance the quality of bone as indicated by increased yield force.     

Developing plant-based vaccines against neglected tropical diseases: Where are we?

Neglected tropical diseases (NTDs) impair the lives of 1 billion people worldwide, and threaten the health of millions more. Although vaccine candidates have been proposed to prevent some NTDs, no vaccine is available at the market yet. Vaccines against NTDs should be low-cost and needle-free to reduce the logistic cost of their administration. Plant-based vaccines meet both requirements: plant systems allow antigen production at low cost, and also yield an optimal delivery vehicle that prevents or delays digestive hydrolysis of vaccine antigens. This review covers recent reports on the development of plant-based vaccines against NTDs. Efforts conducted by a number of research groups to develop vaccines as a mean to fight rabies, cysticercosis, dengue, and helminthiasis are emphasized. Future perspectives are identified, such as the need to develop vaccination models for more than ten pathologies through a plant-based biotechnological approach. Current limitations on the method are also noted, and molecular approaches that might allow us to address such limitations are discussed.     

Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction

In this study venlafaxine was administered to rats at a low, moderate or high dose; for comparison, the selective serotonin reuptake inhibitor (SSRI) sertraline and the tricyclic antidepressant (TCA) amitriptyline were also included. We evaluated, using quantitative autoradiography, the effect of these antidepressant treatments on [35S]GTPgammaS binding stimulated by the 5-HT1A receptor agonist 8-OH-DPAT, a measure of the capacity of 5-HT1A receptors to activate G proteins. Chronic administration of amitriptyline resulted in a marked increase in 5-HT1A receptor-stimulated [35S]GTPgammaS binding in the hippocampus which was accompanied by an increase in 5-HT1A receptor number. 5-HT1A receptor-stimulated [35S]GTPgammaS binding in the hippocampus was also increased by chronic treatment with the highest dose of venlafaxine; 5-HT1A receptor number, however, was not significantly altered. In serotonergic cell body areas (i.e. dorsal and median raphe nuclei), 5-HT1A receptor-stimulated [35S]GTPgammaS binding was not altered by chronic administration of amitriptyline, sertraline or venlafaxine. Chronic TCA treatment does not desensitize somatodendritic 5-HT1A autoreceptor function. However, the lack of effect of chronic sertraline treatment on 5-HT1A receptor-stimulated [35S]GTPgammaS binding is in contrast to what has been observed previously following chronic administration of the SSRI fluoxetine, and suggests that different SSRIs may regulate somatodendritic 5-HT1A autoreceptor function differently depending on their pharmacology. Our data also suggest that the desensitization of somatodendritic 5-HT1A autoreceptors observed in electrophysiological studies following chronic venlafaxine administration is not at the level of receptor-G protein interaction. The hypothermic response in vivo to acute injection of 8-OH-DPAT was significantly attenuated following chronic treatment with venlafaxine or sertraline, but not amitriptyline.     

Cardiac expression of adenine nucleotide translocase-1 in transgenic mice overexpressing bovine GH

Heart hypertrophy is a common finding of acromegaly, a syndrome due to GH excess. Impairment of adenine nucleotide translocase-1 (ANT-1) gene, the main mitochondrial ADP/ATP exchanger, leads to cardiac hypertrophy. The aim of the study was to evaluate cardiac expression and the functional role of ANT-1 in 1- to 12-month-old transgenic mice overexpressing bovine GH (acromegalic mice, Acro) and littermate controls (wild-type mice, Wt). GH specificity of protein degree variation was assessed treating Acro with pegvisomant, a GH receptor competitor. Tissue levels of ANT-1, NF-kappaB, ATP, and lactic acid were evaluated by western blot, bioluminescence, and Fourier transform infrared spectroscopy respectively. The degree of ANT-1 expression was higher in 1-month-old Acro than in Wt (47+/-5% OD vs 33+/-4% OD, P<0 01). On the contrary, ANT-1 expression was lower in 3- to 12-month-old Acro than in Wt (P<0 03). Changes in ANT-1 expression were associated with consistent changes of cellular ATP content, increasing at 1 month (P<0 05) and reducing thereafter in Acro when compared with Wt (P<0 04). Treatment with pegvisomant abolished ANT-1 and ATP changes observed in 1- and 3-month-old Acro, thus supporting a GH-dependent mechanism. Reduced ATP generation in hypertrophied hearts of older Acro was associated with increased lactic acid levels suggesting that part of energy was due to glycolysis. Variations in ANT-1 expression were linked to GH through changes in NF-kappaB, the levels of which changed accordingly. In conclusion, 1-month-old acromegalic mice had increased ANT-1 expression and higher degree of ATP production. Long-standing disease was associated with a consistent reduction of ANT-1 and ATP tissue levels, which became GH-independent in older animals. This study demonstrated a direct effect of GH on key proteins involved in energy metabolism of acromegalic hearts.