The activation of supraspinal GPR40/FFA1 receptor signalling regulates the descending pain control system.

BACKGROUND AND PURPOSE: The ω-3 polyunsaturated fatty acids exert antinociceptive effects in inflammatory and neuropathic pain; however, the underlying mechanisms remain unclear. Docosahexaenoic acid-induced antinociception may be mediated by the orphan GPR40, now identified as the free fatty acid receptor 1 (FFA1 receptor). Here, we examined the involvement of supraspinal FFA1 receptor signalling in the regulation of inhibitory pain control systems consisting of serotonergic and noradrenergic neurons. EXPERIMENTAL APPROACH: Formalin-induced pain behaviours were measured in mice. Antinociception induced by FFA1 receptor agonists was examined by intrathecal injections of a catecholaminergic toxin, 5-HT lowering drug or these antagonists. The expression of FFA1 receptor protein and c-Fos was estimated by immunohistochemistry, and the levels of noradrenaline and 5-HT in the spinal cord were measured by LC-MS/MS. KEY RESULTS: FFA1 receptors colocalized with NeuN (a neuron marker) in the medulla oblongata and with tryptophan hydroxylase (TPH; a serotonergic neuron marker) and dopamine ß-hydroxylase (DBH; a noradrenergic neuron marker). A single i.c.v. injection of GW9508, a FFA1 receptor agonist, increased the number of c-Fos-positive cells and the number of neurons double-labelled for c-Fos and TPH and/or DBH. It decreased formalin-induced pain behaviour. This effect was inhibited by pretreatment with 6-hydroxydopamine, DL-p-chlorophenylalanine, yohimbine or WAY100635. Furthermore, GW9508 facilitated the release of noradrenaline and 5-HT in the spinal cord. In addition, GW1100, a FFA1 receptor antagonist, significantly increased formalin-induced pain-related behaviour. CONCLUSION AND IMPLICATIONS: Activation of the FFA1 receptor signalling pathway may play an important role in the regulation of the descending pain control system.

The analysis of characteristics of elderly people with high VSC level.

OBJECTIVE: The purpose of this study was to examine the characteristics of elderly subjects who had objectionable levels of volatile sulfur compound (VSC). SUBJECTS AND METHOD: In 2002, a total of 115 85-year-old persons in Japan were subjected to oral examinations, tongue coat collections, measurements of VSCs levels inside the mouth using a portable gas chromatography (Oral Chroma, Abilit, Japan), and assessments of quality of life (QOL) using an SF-36 questionnaire. RESULTS: Sixty-six of the subjects were edentulous and 49 were dentulous. They were divided into two groups by VSC levels, those with oral malodor (both H2S > 112 ppb and CH3SH > 26 ppb; subjects with oral malodor, OM group; n = 7) and those without (n = 108). Our results showed that tongue coat deposit amounts and proportion of dentulous subjects were significantly higher in the OM group. Further, in an analysis of QOL, the SF-36 scores for vitality, social functioning and mental health were significantly higher in OM. CONCLUSION: We found that elderly subjects with oral malodor tended to be dentulous and had large deposits of tongue coating. However, oral malodor in the OM group subjects did not appear to cause a disadvantage in their social lives.

A survey of potential risk factors for HIV transmission through dental practice in Japan.

A survey was conducted to find potential risk factors for HIV transmission through dental practice. Self-administered questionnaires were distributed to the members of the dental associations of various prefectures and small cities in Japan. A total of 747 questionnaires was returned by dentists. The findings revealed several problems. Gloves, masks, and other protective garments were generally worn, but most dentists did not always use them during the full course of treatment limiting usage to surgical treatment, and when treating patients in "high-risk groups" and in dental practice the exact percentage of the dentists who reused a used anesthetic liquid cartridge is 12.7%. The effectiveness of the education for dentists regarding AIDS was statistically clarified. It is obviously necessary to provide important information regarding AIDS and HIV transmission to the dentists. Potential risk for HIV transmission through dental practice will be prevented by AIDS education for the dentists.

[A survey on infection control practices, knowledge and attitudes toward AIDS/HIV among dental practitioners].

A survey was conducted in December 1993 by sending questionnaires to all 566 dentists of the Iwate Dental Association. The questionnaires consisted of 68 items including infection control practices, knowledge, and attitudes towards AIDS/HIV. The response rate was 51.1 percent (N = 289). The average age of dentists in the sample was 43.7 +/- 9.5 (S.D.) (range: 28 to 85). Data was evaluated statistically by Kruskal-Wallis test, Mann-Whitney's U test and Chi-square test, and significant differences were observed. Gloves, masks, and other protective garments were generally worn, but most dentists did not always use them during the full course of treatment limiting usage to surgical treatment, and when treating patients in "high-risk groups". Other infection control procedures, such as instrument sterilization, did not comply with the guidelines of the Ministry of Health and Welfare. Two dentists responded that they had treated AIDS patients and three dentists treated possible AIDS/HIV patients in their dental offices. Despite 71.3% expressing a belief that they have a moral responsibility as a dentist to treat AIDS/HIV patients only 15.6% were willing to treat AIDS/HIV patients. Over 40% of the respondents were not certain as to whether they had treated AIDS/HIV patients or not, and over 60% believed AIDS/HIV patients would come to their dental offices in the near future. Therefore, to practice dentistry on AIDS/HIV patients safely, dentists must provide effective infection control in their dental offices on the assumption that all patients are AIDS/HIV positive, and additional information about AIDS/HIV and adequate training on procedures in the care of AIDS/HIV patients are needed.

[A case of pure alexia whose writing ability with eyes closed was superior to that with eyes open].

We compared the writing ability between eyes open (looking at one's writing) and eyes closed (without looking) in a case of pure alexia. The patient is a 84-year-old right handed man who developed pure alexia following an infarction in the distribution of the left posterior cerebral artery. He showed right homonymous hemianopsia, slight memory disorder and slight anomia. He could not read any kinds of letters and words at all though he could categorize letters: Kana (phonograms), Kanji (morphograms) and Arabic numbers, and he could distinguish the real letters from false ones. He could achieve almost 60-70% of Kana and Kanji dictation, though it was not perfect. He was often confused and could not continue writing correct letters once interrupted. He wrote poorly when looking at what he was writing. So we compared the ability of dictation with his eyes closed, and that with his eyes open. We found the former way never caused confusion and got better results, which was statistically significant (Fisher's exact test (p < 0.05)). It seemed that his visual feedback of his own writing rather caused trouble in his writing. Thus we concluded that input (reading) process and output (writing) process work simultaneously and bi-directionally. Slight impairment of writing in pure alexia patients might be caused by the effect of impairment of input (reading) process, which is simultaneously connected with the output (writing) process.

Effect of saline infusion on urinary calcium excretion in essential hypertension.

Urinary excretion of sodium and calcium was examined in hypertensive (n = 8) and normotensive (n = 7) subjects following infusion of 2% saline at a rate of 11 mL/min for 90 min. The urinary sodium excretion was 204 +/- 38 (mean +/- SEM) muEq/min in normotensives and 233 +/- 28 muEq/min in hypertensives before infusion of saline and increased maximally to 499 +/- 114 muEq/min (P less than .05) and to 928 +/- 68 muEq/min (P less than .01), respectively, after saline infusion. In normotensives, urinary calcium excretion did not change significantly; however, in hypertensives excretion increased markedly (P less than .01) from 6.1 +/- 0.7 muEq/min to 12.3 +/- 1.6 muEq/min. Plasma atrial natriuretic peptide (ANP) levels increased significantly (P less than .05) in both groups. Serum ionized calcium and plasma parathyroid hormone (PTH) levels did not change significantly. The increments of urinary sodium and calcium and of plasma ANP, as well as the preinfusion plasma PTH level, were significantly (P less than .05) higher in hypertensives than in normotensives. The present study showed that exaggerated natriuresis was accompanied by hypercalcinuria and an enhanced rise in plasma ANP in hypertensives. Basal levels of plasma PTH were elevated in hypertensives. The calcium deficiency may be attributable to a close relationship between urinary sodium and calcium, and causally related to the disturbance of sodium and volume homeostasis in hypertension, which results in exaggerated natriuresis.

Effects of insulin on plasma renin activity, plasma atrial natriuretic peptide and body fluid volume in diabetes mellitus.

The effects of insulin treatment on plasma renin activity (PRA), plasma atrial natriuretic peptide (ANP) and body fluid volume were studied in 16 hospitalized patients with insulin-independent diabetes mellitus. Parameters were recorded for 2 days during treatment by diet alone and for 3 weeks after starting insulin. Blood samples were obtained weekly from 9 patients for the measurement of fasting plasma glucose, hematocrit, PRA and plasma ANP. A 24-hr urine sample was collected to determine the urinary excretion of glucose and sodium. In a separate group of 7 patients, plasma volume and extracellular fluid volume were determined by the Evans blue and sodium thiocyanate dilution tests, respectively. In the group of 9 diabetic patients, significant (p less than 0.05) reductions in fasting plasma glucose, hematocrit and the urinary excretion of sodium and glucose were seen with insulin treatment. PRA fell significantly (p less than 0.05) from 5.2 +/- 1.2 ng/ml/hr (mean +/- SEM) on the control days to 2.3 +/- 0.5 on the 21st day after starting treatment. Plasma levels of ANP averaged 35 +/- 5 pg/ml on the control days and these did not change significantly. In the other group of 7 patients, both plasma volume and extracellular fluid volume increased significantly (p less than 0.05) with insulin treatment. A sodium-retaining effect of insulin and a decrease in osmotic diuresis may have increased the body fluid volume and caused the fall in PRA. Thus, a vasodilatory action of insulin may assist in compensation for the increase in body fluid volume, preventing a rise in plasma ANP levels.

Body fluid distribution in the maintenance of DOCA-salt hypertension in rats.

Body fluid volumes and their relation to mean arterial pressure and plasma renin activity (PRA) were examined in heminephrectomized rats after 4 wk of treatment with deoxy-corticosterone acetate (DOCA) and placed on one of three levels of salt intake, either high (D-HS), normal (D-NS), or low (D-LS); sham-operated rats, which received heminephrectomy and no DOCA treatment, also received high (S-HS), normal (S-NS), or low (S-LS) intakes of salt. Body fluid volumes were measured as the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water for plasma volume (PV), extracellular fluid volume (EFV), and total body water (TBW), respectively. Approximately the same degrees of hypertension occurred in the D-HS and D-NS rats, but the D-LS rats were normotensive. PV and EFV were increased only in the D-HS rats, with no prominent changes occurring in the D-NS rats. Intracellular fluid volume (ICF) was not changed in the D-NS rats when compared with the S-NS rats. The ratios of PV/EFV and EFV/TBW in the DOCA-treated groups on high or normal salt were not different from their controls. PRA was greatly suppressed in the D-HS and D-NS rats when compared with all other groups. In another group of D-HS rats, sodium was restricted for 2 wk; in this group the mean arterial pressure fell to control levels without significant changes in PV, but interstitial fluid volume was reduced to normal levels. These results demonstrated that 1) in DOCA-salt hypertensive rats there is expansion of body fluid volumes that are proportionally distributed among the PV, EFV, and ICF; 2) increases in body fluid volumes are not necessary for DOCA to maintain hypertension; 3) a certain minimal amount of dietary sodium is necessary for the development and maintenance of hypertension; and 4) following DOCA treatment the suppression of PRA is not due solely to expansion of body fluid volumes.