Very virulent infectious bursal disease virus (vvIBDV) causes high mortality in chickens but measures to reduce the mortality have not been explored. Chickens (8-9 weeks) were treated with 3 agents ...before and during vvIBDV inoculation. Dexamethasone treatment reduced the mortality of infected chickens (40.7% vs. 3.7%;
< 0.001), but treatment with aspirin or vitamin E plus selenium did not affect the mortality. The bursa of Fabricius appeared to have shrunk in both dead and surviving chickens (
< 0.01). The results indicate that dexamethasone can reduce mortality in vvIBDV-infected chickens and may provide therapeutic clues for saving individual birds infected by the virus.
To determine the safety of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG) in patients with clinical stage I gastric cancer in Korea.
There is still a lack ...of large-scale, multicenter randomized trials regarding the safety of LADG.
A large-scale, phase 3, multicenter, prospective randomized controlled trial was conducted. The primary end point was 5-year overall survival. Morbidity within 30 postoperative days and surgical mortality were compared to evaluate the safety of LADG as a secondary end point
: A total of 1416 patients were randomly assigned to the LADG group (n = 705) or the ODG group (n = 711) between February 1, 2006, and August 31, 2010, and 1384 patients were analyzed for modified intention-to-treat analysis (ITT) and 1256 were eligible for per protocol (PP) analysis (644 and 612, respectively). In the PP analysis, 6 patients (0.9%) needed open conversion in the LADG group. The overall complication rate was significantly lower in the LADG group (LADG vs ODG; 13.0% vs 19.9%, P = 0.001). In detail, the wound complication rate of the LADG group was significantly lower than that of the ODG group (3.1% vs 7.7%, P < 0.001). The major intra-abdominal complication (7.6% vs 10.3%, P = 0.095) and mortality rates (0.6% vs 0.3%, P = 0.687) were similar between the 2 groups. Modified ITT analysis showed similar results with PP analysis.
LADG for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complication compared with conventional ODG.
Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the ...interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by alpha2A- and alpha(1A/1L)-adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 microM), a alpha2A-adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the alpha2A-adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.
GABA is a major neurotransmitter in the hypothalamus. In particular, neurons in the paraventricular nucleus (PVN) of the hypothalamus receive dense GABAergic inputs from peri-PVN regions. The ...noradrenergic system has been reported as a modulator of GABAergic transmission to the PVN. Previous electrophysiological and morphological studies support the presence of adrenoceptors on GABAergic neurons innervating the PVN. In this study, we identified three adrenoceptors on GABAergic neurons in the peri-PVN region, focusing on the anterior hypothalamic area (AHA) and rostral zona incerta (ZIr). GABAergic neurons were identified using enhanced green fluorescent protein (eGFP), followed by single cell RT-PCR analysis of the GABA synthetic enzymes, glutamic acid decarboxylase (GAD)65 and/or GAD67. Single cell RT-PCR data revealed the expression of α
1A-, α
1B- and α
2A-adrenoceptor mRNA on GABAergic neurons in AHA and ZIr. Additionally, immunohistochemical studies showed that the immunoreactivities of α
1A-, α
1B- and α
2A-adrenoceptor were colocalized with eGFP-expressing neurons in AHA and ZIr. The present findings suggest the contribution of adrenoceptors to the modulation of GABAergic neurons in AHA and ZIr.
Very virulent infectious bursal disease virus (vvIBDV) causes high mortality in chickens but measures to reduce the mortality have not been explored. Chickens (8-9 weeks) were treated with 3 agents ...before and during vvIBDV inoculation. Dexamethasone treatment reduced the mortality of infected chickens (40.7% vs. 3.7%; p < 0.001), but treatment with aspirin or vitamin E plus selenium did not affect the mortality. The bursa of Fabricius appeared to have shrunk in both dead and surviving chickens (p < 0.01). The results indicate that dexamethasone can reduce mortality in vvIBDV-infected chickens and may provide therapeutic clues for saving individual birds infected by the virus.
Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior ...hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p< 0.01 by χ
2
-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.
Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior ...hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by $x^2$-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.
The hypothalamic paraventricular nucleus (PVN), an integrating site in regulating the neuroendocrine and autonomic nervous systems, is composed of heterogeneous neurons, type I and type II, based on ...their electrophysiological properties. In the present study, the molecular identification of voltage‐gated potassium (Kv) channels was investigated that are relative with a delay in the onset of the first action potential present distinctively in type I neurons. The recorded cells were harvested and followed by single cell RT‐PCR and real‐time PCR analysis. As a result, Kv1.2, Kv1.3, Kv1.4, Kv4.1, Kv4.2 and Kv4.3 were expressed in both type I and type II neurons and the expression density of Kv4.2 and Kv4.3 were significantly higher in type I neurons than in type II. Additionally, co‐expression of Kv1.3, Kv4.2 and Kv4.3 prolonged delay significantly and Kv channel blockers diminished the delaying time in the onset of the first action potential in type I PVN neurons. In conclusion, Kv1.3, Kv4.2 and Kv4.3 are the potential Kv channels responsible for determining the distinct electrophysiological properties of PVN neurons. Support from the National Research Foundation of Korea (2010‐0015531).
The hypothalamic paraventricular nucleus (PVN), an important integrating site in regulating the neuroendocrine and autonomic nervous systems, is composed of heterogeneous neurons. These neurons are ...classified into two groups, type I and type II neurons, based on their electrophysiological properties. In the present study, we investigated the molecular identification of voltage‐gated K (Kv) channels. These are known to be associated with a delay in the onset of the first action potential, which is a distinctive characteristic of type I neurons.
In order to identify the mRNA expression profiles, the PVN neurons were divided into type I and type II neurons according to their electrophysiological properties. The recorded cells were harvested and single‐cell RT‐PCR analysis was performed. The single‐cell RT‐PCR analysis revealed that Kv1.2, Kv1.3, Kv1.4, Kv4.1, Kv4.2, and Kv4.3 were expressed in both type I and type II neurons. The relative quantitative analysis revealed that the expression density of Kv1.2, Kv4.2, and Kv4.3 were significantly higher in type I neurons than in type II neurons. These results suggest that several Kv channels are present in both type I and type II neurons and Kv1.2, Kv4.2 and Kv4.3 are the potential Kv channels responsible for determining the distinct electrophysiological properties. This work is supported by National Research Foundation of Korea (2009‐0067186)
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