Transmission of the highly pathogenic avian influenza virus H5N1 within flocks during the 2004 epidemic in Thailand

This present study is the first to quantify the transmission of avian influenza virus H5N1 within flocks during the 2004 epidemic in Thailand. It uses the flock-level mortality data to estimate the transmission-rate parameter ( beta ) and the basic reproduction number (R(0)). The point estimates of beta varied from 2.26/day (95% confidence interval [CI], 2.01-2.55) for a 1-day infectious period to 0.66/day (95% CI, 0.50-0.87) for a 4-day infectious period, whereas the accompanying R(0) varied from 2.26 (95% CI, 2.01-2.55) to 2.64 (95% CI, 2.02-3.47). Although the point estimates of beta of backyard chickens and fighting cocks raised together were lower than those of laying hens and broiler chickens, this difference was not statistically significant. These results will enable us to assess the control measures in simulation studies. They also indicate that, for the elimination of the virus, a critical proportion of the susceptible poultry population in a flock (i.e., 80% of the population) needs to be vaccinated.     

Effects of estrogen via estrogen receptors on parvalbumin levels in cardiac myocytes of ovariectomized rats

The study investigated the effects of estrogen on parvalbumin (PV) levels in cardiac myocytes of ovariectomized rats, which is a model system for postmenopausal woman. Parvalbumin acts as a relaxing factor in cardiac myocytes. Adult female Wistar rats, 12 weeks old, were randomly divided into 5 groups of 10: sham-operated (SHAM), ovariectomized (OVX), and OVX receiving estrogen replacement of 10 μg/kg (Es10), 20 μg/kg (Es20) and 40 μg/kg (Es40). After 10 weeks, serum estrogen levels were measured and the α and β estrogen receptors in cardiac myocytes were investigated by immunohistochemistry. PV levels were examined by immunohistochemistry and Western blot analysis. Cardiac myocytes of all animals showed strong staining intensities for α immunoreactive (Es α-ir), but weak staining for β immunoreactive (Es β-ir) estrogen receptors. The Es α-ir was reduced in the cardiac myocytes of the OVX groups, but increased in the Es10, Es20 and Es40 groups. We therefore suggest that estrogen effects are mediated via Es α receptors rather than Es β receptors in female rat hearts. Estrogen and PV immunoreactive (PV-ir) levels and the intensity of the PV band observed in the OVX group were less than those of the SHAM group. In the Es10, Es20 and Es40 groups, the increased intensity of the PV-ir and PV bands correlated with the increased estrogen levels. The low PV levels in cardiac myocytes induced by low estrogen were restored by estrogen replacement therapy. Therefore a reduction of PV may lead to diastolic dysfunction in menopause.     

Negative regulation of T cell activation and autoimmunity by the transmembrane adaptor protein LAB

LAB (linker for activation of B cells), also known as NTAL (non-T cell activation linker), is a LAT (linker for activation of T cells)-like adaptor protein that is expressed in B, NK, and mast cells. Its role in lymphocytes has not been clearly demonstrated. Here, we showed that aged LAB-deficient (Lat2(-/-)) mice developed an autoimmune syndrome. Lat2(-/-) T cells were hyperactivated and produced more cytokines than Lat2(+/+) T cells. Even though LAB was absent in naive T cells, LAB could be detected in activated Lat2(+/+) T cells. LAT-mediated signaling events were enhanced in Lat2(-/-) T cells; however, they were suppressed in T cells that overexpressed LAB. Mice with the Lat2 gene conditionally deleted from T cells also developed the autoimmune syndrome like Lat2(-/-) mice. Together, these data demonstrated an important role of LAB in limiting autoimmune response and exposed a mechanism regulating T cell activation.     

Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL

Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcepsilonRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcepsilonRI-mediated signaling than LAT(-/-) mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcepsilonRI-mediated signaling.     

Angiotensin II may mediate apoptosis via AT1-receptors in the rat cardiac conduction system.

INTRODUCTION: Apoptosis and angiotensin II (Ang II) have been suggested as possible causes of arrhythmias. In addition, Ang II via Ang II type I (AT(1)-) receptors, has been demonstrated to induce cardiomyocyte apoptosis. The transgenic m(Ren-2)27 (TG) rat carries the additional Ren-2 gene, the expression of which results in an increase in cardiac Ang II, thus potentially affecting the cell growth/death equilibrium. In this study we have investigated the effect of Ang II, via AT(1)-receptors, on mediating apoptosis in a cardiac conduction system (SA node and AV nodes). MATERIALS AND METHODS: Heart sections from male two-day, one-week and two-week TG and Sprague-Dawley (SD) rats were stained with Masson Trichrome to localise the SA and AV nodes. The sections containing SA or AV nodes were processed for quantitation of apoptotic nuclei and AT(1)-receptors. RESULTS: The number of apoptotic nuclei/mm(2) in the SA and AV nodes were found to decrease from two days to two weeks in both the TG and the SD rats, and the number of apoptotic nuclei/mm(2) in the TG groups was significantly higher than that of the SD groups for all ages (p<0.05). The number of AT(1)-receptors/mm(2) in the SA node were found to decrease with increasing age, whereas the number of AT(1)-receptors/mm(2) in the AV node was increased in both TG and SD rats and the number of AT(1)-receptors/mm(2) in the three TG groups was significantly more than that of the three SD groups (p<0.05). DISCUSSION AND CONCLUSION: As a consequence of the additional renin gene in the TG rats, which results in the alteration of the local renin-angiotensin system, the numbers of AT(1)-receptors/mm(2) and apoptotic nuclei/mm(2) are increased. The number of apoptotic nuclei/mm(2) and AT(1)-receptors/mm(2) in the SA node decrease with maturation, whereas, the number of AT(1)-receptors in the AV node increase. Thus, there may be a correlation between Ang II and apoptosis in the SA node, which does not appear to be present in the AV node.     

The primacy of platelet-rich fibrin on bone regeneration of various grafts in rabbit's calvarial defects

AimsThis study investigated the effect of platelet-rich fibrin (PRF) on bone regeneration of various grafting materials in rabbit calvarial defects.Material and methodsTwo bicortical skull defects were prepared in 20 New Zealand white rabbits; 10 rabbits were treated with PRF and the other 10 were non-PRF. In both groups, autogenous bone was compare to empty defects in 5 rabbits and the composite of autogenous bone and deproteinized bovine bone versus deproteinized bovine bone (DBB) in the other five. The animals were sacrificed at 8 weeks. Bone formation was assessed by radiographic densitometry and histomorphometric analysis.ResultsThe mean optical density (OD) and histomorphometric analysis (HA) of the percentage of new bone showed that the PRF groups were significantly higher than the non-PRF groups in the autogenous bone graft (OD: 0.60 ± 0.19 vs 0.36 ± 0.03; HA: 38.03 ± 4.23 vs 26.21 ± 10.58) and the empty defect (OD: 0.29 ± 0.06 vs 0.11 ± 0.06; HA: 18.81 ± 9.27 vs 6.24 ± 5.01), but not in the DBB group (OD: 1.18 ± 0.17 vs 1.07 ± 0.05; HA: 13.067 ± 3.64 vs 9.63 ± 5.47) and the composite group (OD: 0.81 ± 0.15 vs 0.91 ± 0.05; HA: 22.63 ± 3.61 vs 21.29 ± 3.52).ConclusionsPRF had a positive effect on bone formation when used alone or combined with autogenous bone, but not with deproteinized bovine bone.     

Improving cardiac function with new-generation plasma volume expanders

Background

Plasma expander (PE) based on polyethylene glycol (PEG) conjugated to albumin has shown positive results maintaining blood volume during hemodilution and restoring blood volume during resuscitation from hemorrhagic shock. Polyethylene glycol conjugation to human serum albumin (HSA), PEG-HSA, increases size, weight, and colloidal osmotic pressure, with minor effects on solution viscosity.

Methods

This study was designed to test the hypothesis that PEG-HSA (2 g/dL) produced by direct PEGylation chemistry improves cardiac function during 2 experimental models, (i) moderate hemodilution and (ii) resuscitation from hemorrhagic shock, compared with a conventional colloidal PE (Dextran 70 kd [Dx70], 6 g/dL). Cardiac function was studied using a miniaturized pressure volume conductance catheter implanted in the left ventricle and evaluated in terms of cardiac indices derived from the pressure volume measurements.

Results

Polyethylene glycol–HSA increased cardiac output, stroke volume, and stroke work and decreased systemic vascular resistance compared with Dx70 in both experimental models. The improvements induced by PEG-HSA in cardiac function were sustained over the observation time. Polyethylene glycol–HSA cardiac mechanoenergetics changes are the result of increased energy transferred per stroke and decreased resistance of the vasculature connecting the heart. In summary, PEG-HSA decreased left ventricle ejection impedance.

Conclusion

Ejection of blood diluted with PEG-HSA presented a reduced load to the heart, increased contractile function, and lowered the energy consumed per unit volume compared with Dx70. Our results emphasize the importance of heart function as a parameter to be included in the evaluation changes induced by new PEs.