The adhesion molecule ICAM-1 is overexpressed in patients with Hymenoptera venom allergy and decreases after ultrarush venom immunotherapy

Adhesion molecules, including ICAM-1, are an important factor in allergic inflammation caused by inhalant allergens, but there are no studies investigating their possible role in Hymenoptera venom allergy (HVA). We measured the level of ICAM-1 in 13 venom-allergic patients before and after ultra-rush venom immunotherapy (VIT). Eight patients were treated by yellow jacket venom and 5 were treated by honeybee venom. Serum ICAM-1 levels were assayed by an immunoenzymatic method, with a detection limit of 0.35 ng/ml. The mean level of ICAM-1 changed from 316.4±78.2 ng/ml before VIT to 294.7±77.9 after VIT. This difference was statistically significant (p = 0.019). These findings show that in patients with HVA there is an over-expression of ICAM-1, and that ultra-rush VIT significantly decreases ICAM-1 levels. It is likely that the known ability of VIT to correct the imbalance in T lymphocytes subpopulations and in the associated production of cytokines may account for this observation. In fact, such cytokines include IL-4 and TNF-alpha, that up-regulate adhesion molecules.     

Mitral leaflet modeling: Importance of in vivo shape and material properties

The anterior mitral leaflet (AML) is a thin membrane that withstands high left ventricular (LV) pressure pulses 100,000 times per day. The presence of contractile cells determines AML in vivo stiffness and complex geometry. Until recently, mitral valve finite element (FE) models have neglected both of these aspects. In this study we assess their effect on AML strains and stresses, hypothesizing that these will differ significantly from those reported in literature. Radiopaque markers were sewn on the LV, the mitral annulus, and AML in sheep hearts, and their four-dimensional coordinates obtained with biplane video fluoroscopy. Employing in vivo data from three representative hearts, AML FE models were created from the marker coordinates at the end of isovolumic relaxation assumed as the unloaded reference state. AML function was simulated backward through systole, applying the measured trans-mitral pressure on AML LV surface and marker displacements on AML boundaries. Simulated AML displacements and curvatures were consistent with in vivo measurements, confirming model accuracy. AML circumferential strains were mostly tensile (1-3%), despite being compressive (-1%) near the commissures. Radial strains were compressive in the belly (-1 to -0.2%), and tensile (2-8%) near the free edge. These results differ significantly from those of previous FE models. They reflect the synergy of high tissue stiffness, which limits tensile circumferential strains, and initial compound curvature, which forces LV pressure to compress AML radially. The obtained AML shape may play a role not only in preventing mitral regurgitation, but also in optimizing LV outflow fluid dynamics.     

A common cortical substrate activated by horizontal and vertical sound movement in the human brain

Perception of movement in acoustic space depends on comparison of the sound waveforms reaching the two ears (binaural cues) as well as spectrotemporal analysis of the waveform at each ear (monaural cues). The relative importance of these two cues is different for perception of vertical or horizontal motion, with spectrotemporal analysis likely to be more important for perceiving vertical shifts. In humans, functional imaging studies have shown that sound movement in the horizontal plane activates brain areas distinct from the primary auditory cortex, in parietal and frontal lobes and in the planum temporale. However, no previous work has examined activations for vertical sound movement. It is therefore difficult to generalize previous imaging studies, based on horizontal movement only, to multidimensional auditory space perception. Using externalized virtual-space sounds in a functional magnetic resonance imaging (fMRI) paradigm to investigate this, we compared vertical and horizontal shifts in sound location. A common bilateral network of brain areas was activated in response to both horizontal and vertical sound movement. This included the planum temporale, superior parietal cortex, and premotor cortex. Sounds perceived laterally in virtual space were associated with contralateral activation of the auditory cortex. These results demonstrate that sound movement in vertical and horizontal dimensions engages a common processing network in the human cerebral cortex and show that multidimensional spatial properties of sounds are processed at this level.     

Characterisation of a Colombian granulovirus (Baculoviridae: Betabaculovirus) isolated from Spodoptera frugiperda (Lepidoptera: Noctuidae) larvae

A strategy for biological control of the fall armyworm, Spodoptera frugiperda, has included the use of baculoviruses principally the nucleopolyhedrovirus SfMNPV, which have been extensively characterised. In contrast, the granulovirus of S. frugiperda (SfGV) has been poorly studied even though it is able to enhance the infectivity and virulence of NPVs. In this work, a Colombian SfGV isolate (VG008) was characterised in comparison with a reference isolate from Brazil (VG014). The viral morphology was characterised by ovoidal-shaped occlusion bodies (OB) that contained one single internal virion. Median lethal concentrations (LC₅₀) and mean times to death (MTD) were 4.5 × 10⁵ OBs/mL and 29 days for VG008 and 1.6 × 10⁵ OBs/mL and 33 days for VG014. Both isolates reduced their insecticidal activity by 94%, after one hour of direct irradiation with ultraviolet light type B. The most prominent protein had an apparent molecular mass of 27 kDa and corresponded with the Granulin. Genomic comparison among isolates from Colombia and Brazil generated by restriction profiles showed differences in the number and size of fragments. Partial sequences of lef-8 and lef-9 genes and complete sequence of gran gene of Colombian SfGV isolate (VG008) showed high similarity values with VG014 and SfGV A12-4 homologous sequences, showing genetic distance lower than 0.015 (Kimura 2-parameter model), which confirmed that the three isolates belong to the same viral species. The characterisation of VG008 isolate demonstrated its high genomic and biological similarity with the Brazilian isolate.     

Weight Loss and Premature Death: The 1946 British Birth Cohort Study

Objective

The relationship between weight loss and mortality has important clinical and public health significance but has proved to be complex. Evidence is mixed and particularly limited on the association between weight loss in mid-life and premature death (i.e. before 65 years of age), a small albeit important segment of total mortality. We aimed to study the association between midlife weight change and mortality accounting for health and lifestyle characteristics, and also considering potential bias due to preexisting chronic diseases and smoking status.

Design

Longitudinal, population-based, ‘the 1946 British’ birth cohort study.

Subjects and Measures

In 2750 men and women, mortality from age 53 through 65 years was analyzed according to categories of measured 10 year weight change between 43 and 53 years. Cox''s hazard ratios (HR) were progressively adjusted for socio-demographic, lifestyle and health characteristics.

Results

Nearly 20% of participants lost weight and over 50% gained 5 kg or more in midlife. There were 164 deaths. Compared to those who gained between 2 and 5 kg, those who lost 5 kg or more had an increased risk of premature death independently of midlife physical activity, socio-economic circumstances and educational attainment. This association was unaltered when highest weight loss (lost more than 15 Kg) (p = 0.04) and early deaths were excluded (p<0.001), but was no longer significant after adjustment for cardiovascular risk factors and health status (HR = 1.8; 95% CI: 0.9 to 3.5).

Conclusion

The inverse association between weight loss in midlife and higher risk of premature death may be explained by vascular risk factors and ill health. In consideration of the burden of premature death, closer monitoring of weight loss in mid-life is warranted.     

Effects of Dipeptidyl-Peptidase 4 Inhibitor about Vascular Inflammation in a Metabolic Syndrome Model

Background

In this study, we used vidagliptin(V) to examine the role of the DDP-IV, incretin system component, in the activation of different molecular inflammatory cytokines, NF-kB and VCAM-1 to generate a microenvironment that supports cardiovascular remodeling.

Methods

Male WKY and SHR were separated into five groups: Control, FFR: WKY rats receiving a 10% (w/v) fructose solution during all 12 weeks, SHR, FFHR: SHR receiving a 10% (w/v) fructose solution during all 12 weeks and FFHR+V: (5 mg/kg per day for 6 weeks) (n = 8 each group). Metabolic variables and systolic blood pressure were measured. The TBRAS, eNOS activity, and NAD(P)H oxidase activity were estimated to evaluate oxidative stress. Cardiac and vascular remodeling were evaluated. To assess the cytokine, NF-kB and VCAM-1 immunostaining techniques were used.

Results

The FFHR experimental model presents metabolic syndrome criteria, vascular and cardiac remodeling, vascular inflammation due to increased expression of NF-kB, VCAM-1, and pro-atherogenic cytokines. Chronic treatment with V was able to reverse total or partiality of variables studied.

Conclusions

Data demonstrated an important effect of DDP-IV in reducing vascular inflammation, accompanied by a favorable reduction in metabolic and structural parameters.