Allyl isothiocyanates and cinnamaldehyde potentiate miniature excitatory postsynaptic inputs in the supraoptic nucleus in rats

Allyl isothiocyanates (AITC) and cinnamaldehyde are pungent compounds present in mustard oil and cinnamon oil, respectively. These compounds are well known as transient receptor potential ankyrin 1 (TRPA1) agonists. TRPA1 is activated by low temperature stimuli, mechanosensation and pungent irritants such as AITC and cinnamaldehyde. TRPA1 is often co-expressed in TRPV1. Recent study showed that hypertonic solution activated TRPA1 as well as TRPV1. TRPV1 is involved in excitatory synaptic inputs to the magnocellular neurosecretory cells (MNCs) that produce vasopressin in the supraoptic nucleus (SON). However, it remains unclear whether TRPA1 may be involved in this activation. In the present study, we examined the role of TRPA1 on the synaptic inputs to the MNCs in in vitro rat brain slice preparations, using whole-cell patch-clamp recordings. In the presence of tetrodotoxin, AITC (50μM) and cinnamaldehyde (30μM) increased the frequency of miniature excitatory postsynaptic currents without affecting the amplitude. This effect was significantly attenuated by previous exposure to ruthenium red (10μM), non-specific TRP channels blocker, high concentration of menthol (300μM) and HC-030031 (10μM), which are known to antagonize the effects of TRPA1 agonists. These results suggest that TRPA1 may exist at presynaptic terminals to the MNCs and enhance glutamate release in the SON.     

Food residues identified in the pharynx of a patient with a cleft palate

Solid food residues were identified in the pharynx of a 17-month-old infant with a cleft palate at the time of anesthesia induction, although nothing-by-mouth directions for more than four hours had been strictly followed. Preoperative airway management, e.g. gargling and nose blowing, is necessary in patients with a cleft palate even after an appropriate period of fasting because food residues may remain in the nose due to the anatomical abnormality.     

Up-regulation of CD40 with juxtacrine activity in human nonsmall lung cancer cells correlates with poor prognosis

BACKGROUND: CD40 and its ligand, CD154, play a regulatory role in several signaling pathways among lymphocytes. Recently, it was reported that CD40 is expressed in several malignant tumors. However, the clinical impact of CD40 expression in nonsmall cell lung cancer has not been studied widely. METHODS: One hundred twenty-nine surgical specimens of nonsmall cell lung cancer were assessed immunohistochemically for CD40 and CD154 expression, and that expression was correlated with patients' clinicopathologic parameters and outcome. Subsequently, in vitro analysis of CD40-CD154 signaling was performed. RESULTS: Immunohistochemical staining of tumor cells confirmed that 67 patients (51.9%) were positive for CD40, and 76 patients (58.9%) were positive for CD154. The survival of patients who had tumors that were negative for CD40 was significantly better than the survival of patients who had tumors that were positive for CD40 (P = .0004). Multivariate analysis using a Cox regression model indicated that CD40 expression in cancer cells is an independent, unfavorable prognostic factor (risk ratio, 1.855; P = .0403). By using an in vitro juxtacrine growth factor assay, the growth of LK2 cells (CD40-positive/CD154-negative) was accelerated by CD154-positive cancer cells, such as PC10 cells (CD40-negative/CD154-positive), by a juxtacrine mechanism. CONCLUSIONS: The current results suggested that CD40 expression in tumors is associated with a poor prognosis and that the juxtacrine interaction of CD40-CD154 among cancer cells facilitates the development of malignant potential in nonsmall cell lung cancer.     

A lower serum level of middle-molecular-weight adiponectin is a risk factor for endometrial cancer

Background

The present study was undertaken to examine the correlation between serum levels of adiponectin isoforms and the risk for endometrial cancer.

Methods

This retrospective case–control study included 43 Japanese women with endometrial cancer and 62 Japanese women with no history of cancer. Serum levels of total adiponectin and the respective isoforms were determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was performed on the serum levels of total adiponectin and its isoforms, high molecular weight, middle molecular weight, and low molecular weight adiponectins, after adjustment for confounders (age, body mass index, hypertension, and diabetes mellitus).

Results

The distribution of body mass index revealed a statistically significant difference between patients and controls (P = 0.001). A statistically significant difference (P < 0.01) was also found in the incidence of diabetes mellitus between the two groups, although there was no significant difference in the incidence of hypertension. In controls, an inverse correlation was observed between body mass index and serum adiponectin levels. However, in patients, an inverse correlation was found only between body mass index and serum middle molecular weight adiponectin level. After adjustment for confounding variables, the factor found to be most closely associated with endometrial cancer was a lower serum level of middle molecular weight adiponectin (adjusted odds ratio 4.89, 95 % confidence interval value 1.25–19.11, P = 0.022).

Conclusion

Low serum level of middle molecular weight adiponectin was the only independent risk factor for endometrial cancer suggesting that the application of adiponectin might prevent or decrease the risk for endometrial cancer.     

Centrally administered ghrelin potently inhibits water intake induced by angiotensin II and hypovolemia in rats

Ghrelin is a potent, centrally acting orexigenic hormone. Recently, we showed that centrally administered ghrelin is a potent antidipsogenic hormone in 24-h water deprived rats. In this study, we examined the effect of intracerebroventricular (icv) injection of ghrelin on angiotensin II (AII)-induced water intake in rats. We also examined the effects of icv injection of ghrelin on drinking induced by intraperitoneal injection of an isotonic polyethylene glycol (PEG) solution that causes isotonic hypovolemia. Water intake induced by the icv injection of AII or ip injection of PEG was significantly reduced after icv injection of ghrelin, although food intake was stimulated by the hormone. The drinking induced by AII was also inhibited by the icv administration of 4α-phorbol 12, 13-didecanoate, an agonist of the osmosensitive TRPV4 channel. This study showed that ghrelin is a potent antidipsogenic peptide by antagonizing general dipsogenic mechanisms including those activated by AII and hypovolemia in rats.     

Mapping of the HLA-linked genes controlling the susceptibility to Takayasu's arteritis

To further define the HLA-linked genes controlling the susceptibility to Takayasu's arteritis, polymorphisms in five microsatellites around the HLA-B and MICA genes, C1-2-A, MIB, C1-4-1, C1-2-5, and C1-3-1, were investigated in 91 Japanese patients with Takayasu's arteritis and 248 healthy Japanese controls. It was found that allele 238 of C1-2-A [60.4% in patients vs. 29.8% in controls, odds ratio (OR)=3.59, P(c)<0.000004], allele 332 of MIB (22.0% vs. 6. 1%, OR=4.32, P(c)<0.0003), allele 208 of C1-2-5 (47.3% vs. 24.6%, OR=2.75, P(c)=0.001), and allele 291 of C1-3-1 (62.6% vs. 44.8%, OR=2.07, P(c)<0.02) were significantly associated with the disease. Combined analyses of polymorphisms in the HLA-B and MICA genes with those in the microsatellites suggest that there are two different disease-susceptible loci for Takayasu's arteritis; one is mapped near the C1-2-A locus and the other is more closely linked to the HLA-B gene than to the MICA gene, because there are at least two different disease-associated HLA-B haplotypes, HLA-B*52 and -B*39.2 haplotypes, in which the disease-associated C1-2-A allele is shared in common.     

Electrophysiological Identification of the Functional Presynaptic Nerve Terminals on an Isolated Single Vasopressin Neurone of the Rat Supraoptic Nucleus

Release of arginine vasopressin (AVP) and oxytocin from magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) is under the control of glutamate‐dependent excitation and GABA‐dependent inhibition. The possible role of the synaptic terminals attached to SON neurones has been investigated using whole‐cell patch‐clamp recording in in vitro rat brain slice preparations. Recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of MNCs at the synaptic level in the SON. In the present study, excitatory glutamatergic and inhibitory GABAergic synaptic inputs were recorded from an isolated single SON neurone cultured for 12 h, using the whole‐cell patch clamp technique. Neurones expressed an AVP‐enhanced green fluorescent protein (eGFP) fusion gene in MNCs. In addition, native synaptic terminals attached to a dissociated AVP‐eGFP neurone were visualised with synaptic vesicle markers. These results suggest that the function of presynaptic nerve terminals may be evaluated directly in a single AVP‐eGFP neurone. These preparations would be helpful in future studies aiming to electrophysiologically distinguish between the functions of synaptic terminals and glial modifications in the SON neurones.