Clinical outcome after 36 months of treatment with injections of autologous blood for recurrent dislocation of the temporomandibular joint.

We investigated the prognosis after three years of treatment for recurrent dislocation of the temporomandibular joint with autologous blood given intravenously in 21 patients with a mean (range) age 64 (17-92) years of whom 16 had coexisting systemic disease. The mean (range) follow up from the first injection was 64 (41-99) months. Eighteen patients had no recurrence during the first 36 months after their first injection, which showed that this minimally-invasive treatment was effective, particularly for those who had conditions that made a mouthpiece or operation unsuitable.

Docosahexaenoic acid promotes neuronal differentiation by regulating basic helix-loop-helix transcription factors and cell cycle in neural stem cells.

Recent studies have suggested that docosahexaenoic acid (DHA) enhances neuronal differentiation of neural stem cells (NSCs) isolated from rat embryonic day 14.5. However the underlying mechanism remains largely unknown. One hypothesis supported by DHA controls the expression level of basic helix-loop-helix (bHLH) transcription factors, such as hairy and enhancer of split 1 (Hes1), Mash1, neurogenin1, and NeuroD; another is that previous studies in retinal progenitor cells DHA affects the cell cycle. In this study, we show that treatment with DHA under differentiation conditions without basic fibroblast growth factor, (1) increases Tuj-1 and MAP2 positive cells in NSCs, (2) that the expression level of Hes1 mRNA and protein decreased significantly from day 1 to day 4, on the other hand, the NeuroD mRNA expression level increased from day 1 to day 4 after treatment with DHA and (3) decreased the percentage of S-phase cells, which correlated with prolonged expression of cyclin-dependent kinase inhibitor p27(kip1), suggesting that DHA enhances neuronal differentiation of NSCs, in part, by controlling the bHLH transcription factors and promoting cell cycle exit. We therefore speculate that DHA is one of the essential key molecules for neuronal differentiation of NSCs.

Chronic administration of docosahexaenoic acid improves the performance of radial arm maze task in aged rats.

1. In the present study, we investigated the effect of docosahexaenoic acid (DHA) on spatial memory related learning ability in aged (100 weeks) male Wistar rats. 2. Rats were fed a fish oil-deficient diet through three generations and were then randomly divided into two groups. Over 10 weeks, one group was per orally administered 300 mg/kg per day DHA dissolved in 5% gum Arabic solution and the other group was administered the vehicle alone. Five weeks after the start of the administration, rats were tested with the partially baited eight-arm radial maze to estimate two types of spatial memory related learning ability displayed by reference memory error and working memory error. 3. Chronic administration of DHA significantly decreased the number of reference memory errors and working memory errors. 4. The level of lipid peroxide (LPO) in the hippocampus tended to decrease with chronic DHA administration and demonstrated a positive correlation with the number of reference memory errors. 5. These results suggest that the accumulation of hippocampal LPO reduces spatial memory related learning ability in aged rats. Moreover, chronic administration of DHA was effective in decreasing the level of hippocampal LPO, then improving learning ability.

Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats.

Wistar rats were fed a fish oil-deficient diet through three generations. The young (five-week-old) male rats of the third generation were randomly divided into two groups. Over 10 weeks, one group was perorally administered docosahexaenoic acid dissolved in 5% gum Arabic solution at 300 mg/kg/day; the other group received a similar volume of vehicle alone. Five weeks after starting the administration, the rats were tested for learning ability related to two types of memory, reference memory and working memory, with the partially (four of eight) baited eight-arm radial maze. Reference memory is information that should be retained until the next trial. Working memory is information that disappears in a short time. Entries into unbaited arms and repeated entries into visited arms were defined as reference memory errors and working memory errors, respectively. Docosahexaenoic acid administration over 10 weeks significantly reduced the number of reference memory errors, without affecting the number of working memory errors, and significantly increased the docosahexaenoic acid content and the docosahexaenoic acid/arachidonic acid ratio in both the hippocampus and the cerebral cortex. In addition, the ratio demonstrated a significantly negative correlation with the number of reference memory errors. These results suggest that chronic administration of docosahexaenoic acid is conducive to the improvement of reference memory-related learning ability, and that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus or the cerebral cortex, or both, may be an indicator of learning ability.

Hypotension induced by exercise is associated with enhanced release of adenyl purines from aged rat artery.

To determine whether the antihypertensive effects of exercise are associated with release of ATP and its metabolites from arteries, we assayed blood pressure and the release of adenine nucleotides and nucleosides from the caudal arteries of exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill for 12 wk significantly decreased the rise in systolic and diastolic blood pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of oleic, linoleic, and linolenic acids in the caudal artery decreased significantly with exercise, demonstrating an association between exercise and the unsaturation index of caudal arterial fatty acids. The amounts of total adenyl purines released by the arterial segments from exercised rats, both spontaneously and in response to norepinephrine, were significantly greater by 80.0 and 60.7%, respectively, than those released by tissues from sedentary rats. These results suggest that exercise alters the membrane fatty acid composition in aged rats as well as the release of ATP from vascular endothelial cells and that these factors are associated with the regression of the rise in blood pressure normally observed with advanced age.

Association of age-related decrease in platelet membrane fluidity with platelet lipid peroxide.

The influence of age on platelet lipid peroxide (LPO), platelet membrane fluidity and the composition of fatty acid was investigated in female Wistar rats widely ranging in age from 14 to 720 days old. LPO levels were significantly higher (p<0.05) in the platelets of upper age groups than in those of lower age groups, showing a significantly positive correlation with age (r=0.84, p<0.0001). Membrane fluidity, assessed by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization, was significantly reduced with age. The composition of fatty acid demonstrated an age-related elevation (p<0.05) in the unsaturation index. The rises in the LPO levels revealed a significantly positive correlation with DPH-polarization (r=0.73, p<0.0001). Thus our results suggested that the age-related deterioration of platelet membrane fluidity, despite a significant elevation in the unsaturation index, was due to the age-related higher basal levels of LPO in platelets.

Antioxidative effects of docosahexaenoic acid in the cerebrum versus cerebellum and brainstem of aged hypercholesterolemic rats.

Female Wistar rats (100 weeks old) were divided into two groups; one group was fed a high-cholesterol diet (HC) and the other a high-cholesterol diet plus docosahexaenoic acid (HC-fed DHA rats). Fatty acid concentrations in brain tissues were analyzed by gas chromatography. In the HC-fed DHA rats, brain catalase (CAT), GSH, and glutathione peroxidase (GPx) increased in the cerebrum but not in the brainstem or cerebellum. The rate of increase was 23.0% for CAT, 24.5% for GSH, and 26.3% for GPx compared with that in the HC animals (p < 0.05). In the cerebrum of the HC-fed DHA rats, CAT and GPx increased, with an increase in the ratio of DHA to arachidonic acid. The cerebrum, unlike the other areas of the brain, seems to be more sensitive to DHA in stimulating CAT and GPx. We suggest that DHA plays an important role in inducing an antioxidative defense against active oxygen by enhancing the cerebral activities of CAT, GPx, and GSH.

The hypotensive effect of docosahexaenoic acid is associated with the enhanced release of ATP from the caudal artery of aged rats.

Fish oils have been shown to lower blood pressure in hypertensive subjects. To determine the mechanism of this hypotensive effect, we examined the effects of docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP, AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats (100 wk) were fed a high cholesterol diet and were administered intragastrically ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA group) or vehicle alone (control group). Compared with the controls, rats supplemented with DHA had significantly greater (10.1%) DHA concentrations in the caudal arteries. This was associated with more total (n-3) arterial fatty acids, a greater unsaturation index of arterial fatty acids, 43.9% lower plasma noradrenaline levels and the repression of the elevation in blood pressure observed with advancing age. The amount of purines released, both spontaneously and in response to noradrenaline, from arterial segments of DHA-supplemented rats was significantly higher than that released from tissues of control rats. Regression analysis revealed significant negative relationships between the total amount of purines released from the artery and the systolic (SBP) and diastolic (DBP) blood pressures. These results suggest that in aged rats, supplementation with DHA alters the membrane fatty acid composition as well as the amount of ATP released from vascular endothelial cells and decreases plasma noradrenaline, and that these factors may ameliorate the rise in blood pressure normally associated with advancing age.

Long-term supplementation with a high cholesterol diet decreases the release of ATP from the caudal artery in aged rats.

We examined the effects of high cholesterol (HC) diet on the spontaneous and noradrenaline-induced release of ATP, ADP, AMP and adenosine from caudal arteries and on the plasma levels of these adenyl purines in aged (100-week-old) Wistar rats. Administration of this diet for 12 weeks significantly reduced spontaneous and noradrenaline (1 micromol/L)-evoked release of adenyl purines from the caudal arteries relative to rats given the control diet The unsaturation index of fatty acids (UI), which gives the average number of double bonds, of both the plasma and the caudal artery was significantly less in the HC diet-fed rats than in those fed the control diet. The HC diet for 12 weeks produced a slight but significant increase in systolic and diastolic blood pressure with advancing age. Regression analysis revealed a significant inverse relationship between the total amount of purines released from the artery and diastolic blood pressure, and also a positive relationship between the total amount of purines released and the UI of the caudal artery. These results suggest that the high cholesterol diet decreased the release of adenyl purines from the caudal arteries of aged rats, leading to an increase in blood pressure.

Age-related changes in aortic sensitivity to noradrenaline and acetylcholine in rats.

1. The purpose of the present study was to determine the relationship between plasma and tissue lipid levels and the effects of age on vascular responses to noradrenaline (NA) and acetylcholine (ACh). 2. Studies were performed in young and aged rats and the response of endothelium-intact and -denuded aortic rings to NA and to ACh was measured. The plasma concentration of cholesterol (total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)) and 17 beta-oestradiol was determined, as was the aortic tissue content of phospholipids, cGMP and cholesterol (total, free and esterified). 3. Levels of all types of cholesterol in plasma and aorta increased with age; cholesterol levels in plasma correlated with those in the aorta; levels of phospholipid in the aorta did not increase with age but correlated with those of LDL cholesterol in plasma; levels of 17 beta-oestradiol did not change, but those of cGMP increased with age. 4. In endothelium-intact rings, the maximum tension developed by exposure to NA did not change, but the EC50 of NA increased with age and correlated with total cholesterol in the plasma and with the levels of all types of cholesterol in the aorta. In rings precontracted with NA, age decreased the maximum relaxation induced by ACh. The EC50 of ACh decreased with age and was inversely correlated with levels of cholesterol in the plasma and aorta. Treatment with NA increased cGMP levels in aged rats. Removal of the endothelium abolished the response to ACh and heightened the sensitivity to NA in young and aged rats. 5. Aortic endothelial cells seem to inhibit amine-induced contraction, while age-related changes in the levels of cholesterol in aortic tissue affect the sensitivity of the tissue to NA and ACh.