Involvement of dopamine D2 receptors in the induction of long-term potentiation in the basolateral amygdala-dentate gyrus pathway of anesthetized rats

We have previously found that synaptic pathway from the basolateral amygdala (BLA) to the dentate gyrus (DG) displays N-methyl-D-aspartate (NMDA) receptor-independent form of long-term potentiation (LTP), which should be a valuable model for elucidating neural mechanisms linking emotion and memory. To explore its cellular mechanisms, we investigated possible involvement of the beta-adrenergic, muscarinic cholinergic and dopaminergic systems on LTP in this pathway of anesthetized rats. The induction of BLA-DG LTP was not affected by administration of the beta-adrenoceptor antagonist propranolol (50-150nmol, i.c.v.), the muscarinic receptor antagonist scopolamine (2-6mg/kg, i.p.), the cholinesterase inhibitor physostigmine (50 nmol, i.c.v.) or the dopamine D(1) receptor antagonist SCH23390 (100nmol, i.c.v.), but significantly inhibited by the dopamine D2 receptor antagonists, chlorpromazine (15nmol, i.c.v.) and haloperidol (0.15-0.5mg/kg, i.p.), and significantly promoted by the dopamine D2 receptor agonist quinpirole (78nmol, i.c.v.). Furthermore, lesioning with 6-hydroxydopamine of the ventral tegmental area (VTA), the origin of mesolimbic dopaminergic neurons, resulted in attenuated BLA-DG LTP. These results suggest that the D2-dopaminergic system, but not the beta-adrenergic, muscarinic or D1-dopaminergic system, is involved in the induction of BLA-DG LTP. In addition, inhibition of BLA-DG LTP by haloperidol or VTA lesion was abolished by blockade of GABAergic inhibition with picrotoxin. It is probable that the D2-dopaminergic system promotes the induction of BLA-DG LTP by suppressing GABAergic inhibition.     

Efficacy of a high FFP:PRBC transfusion ratio on the survival of severely injured patients: a retrospective study in a single tertiary emergency center in Japan

Purpose

Recent studies have shown increased survival benefits when a high fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratio is used during trauma resuscitation. However, some reports have raised questions about the effect of higher FFP:PRBC transfusion ratios. The aim of this study was to examine the efficacy of high FFP:PRBC ratios in injured patients with regard to survival and morbidity in a single tertiary emergency center in Japan.

Methods

This study examined severe trauma patients who received 10 or more PRBC units during the first 24 h of admission. We examined the relationship between the FFP:PRBC ratios during the first 6 h and the patient outcome.

Results

The severity was similar among all groups. The mortality rate was 44.4 % in the high (>1:1.5), 16.7 % in the middle (1:1.5–1:2) and 33.3 % in the low (<1:2) F:P ratio groups. Only one patient in the high group developed sepsis, and none of the patients developed ARDS.

Conclusions

The current results indicate that the FFP:PRBC ratios during the first 6 h after admission might not affect the mortality or morbidity. However, differences between trauma care systems in Japan and other countries, along with other study limitations, necessitate that a subsequent prospective multicenter study be undertaken before any definitive conclusions can be made.     

Nerve growth factor-mediated sexual differentiation of the rat hypothalamus

Injection of antibody to nerve growth factor into the cerebral lateral ventricle blocked testosterone-induced behavioral defeminization of neonatal female rats. When tested as adults following ovariectomy and combined estrogen-progesterone treatment, the injected animals showed a significantly higher lordosis quotient than the testosterone-treated, normal rabbit serum-infused controls. Failure of vaginal opening and clitoral enlargement manifested the well-documented masculinizing effect of testosterone on the genitalia in the experimental as well as the control animals. Estrogen sensitivity of hypothalamic neurons which are responsible for the induction of lordosis was retained in the experimental animals. Recordings of the antidromic action potentials from neurons in the ventromedial nucleus of the hypothalamus following stimulation of the midbrain central gray revealed that estrogen decreased the antidromic activation threshold and shortened the absolute refractory period of the hypothalamic efferents along with the estrogen-induced behavioral activation in the experimental animals. In the control group, the estrogen-induced neuronal activation was lost altogether with the behavioral activation.     

Post-keloidectomy irradiation using high-dose-rate superficial brachytherapy

A study was conducted to evaluate the early results of high-dose-rate superficial brachytherapy (HDR-SB) after keloidectomy. Between April 2008 and April 2009, 21 patients with 36 histologically confirmed keloids were treated with postoperative HDR-SB. The tube applicator was placed on the skin to match the area of the surgical wound, and a spacer 5 mm thick was placed between the skin and the applicator. A dose evaluation point was established below 2 mm from skin surface, and 20 Gy was delivered in 4 daily fractions to keloidectomy scars on the anterior chest wall, scapular region, lower jaw and suprapubic region. A dose of 15 Gy was delivered in 3 daily fractions to lesions in other areas. The median follow-up period was 18 months (range, 9 to 29 months). Therapeutic outcome was judged in terms of recurrence, control, or acute side effects. Three keloids (9.7%) in two patients showed local recurrence, with a median time to failure after HDR-SB of 12 months. All recurrences affected the anterior chest wall. Dysraphia occurred in only one patient with an anterior chest wall lesion. Excluding the cases of recurrence, acceptable cosmetic results were achieved. Our results indicate that HDR-SB is effective and safe for preventing recurrence of keloids.     

Biphasic tracheal relaxation induced by higenamine and nantenine from Nandina domestica Thunberg

We compared the effects of the extract from fruits of Nandina domestica Thunberg (NDE) and its constituents, higenamine and nantenine, on contractile responses in isolated guinea-pig trachea. NDE (1 mg/ml) caused biphasic relaxation of the trachea precontracted with high-K(+) stimulation: the fast component was blocked by propranolol and mimicked by higenamine; and the slow was resistant to propranolol and mimicked by nantenine. Ca(2+)-induced contraction under high-K(+) stimulation was antagonized by nantenine or NDE + propranolol. These results suggest that NDE relaxes the trachea quickly through β-adrenoceptor stimulation by higenamine and slowly through Ca(2+) antagonism by nantenine.     

Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory

Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders.