Age-related alteration of expression and function of TLRs and NK activity in oral candidiasis.

OBJECTIVE: Roles of aging or immune responses mediated by Toll-like receptors and natural killer cell in the onset or progression of human candidiasis remain unclear. This study was designed to elucidate the roles using peripheral blood mononuclear cells from healthy donors and patients with oral candidiasis. SUBJECTS AND METHODS: Subjects tested were healthy volunteers and patients who visited Dental Clinical Division of Hokkaido University Hospital. The patients with oral candidiasis included 39 individuals (25-89 years of age) with major complaints on pain in oral mucosa and/or dysgeusia. Healthy volunteers include students (25-35 years of age) and teaching staffs (50-65 years of age) of Hokkaido University Graduate School of Dental Medicine. RESULTS: Functions of Toll-like receptors 2 and 4 were downregulated significantly and the natural killer activity was slightly, but not significantly downregulated in aged healthy volunteers compared with healthy young volunteers. Functions of Toll-like receptors 2 and 4 and the natural killer activity were significantly downregulated in patients with oral candidiasis compared with healthy volunteers. CONCLUSION: Downregulation of functions of Toll-like receptors 2 and 4 as well as natural killer activity is suggested to be associated with the onset or progression of oral candidiasis in human.

Relation between changes in serum hypoxanthine levels by exercise and daily physical activity in the elderly.

Effect of exercise at mild intensity on the serum levels of hypoxanthine was studied in eleven healthy elderly subjects. They were divided into the active and sedentary groups according to their daily physical activity. They performed exercise testing to walk for 5 minutes keeping heart rate at approximately 70% of the maximum heart rate. Mean intensity of exercise estimated according to Karvonen's formula in the active or sedentary group was 41.8 +/- 9.6% or 34.1 +/- 6.1%, respectively. In the sedentary group, the serum hypoxanthine levels at 10 minutes after completion of walk load was significantly higher than that before exercise. Changes in the serum hypoxanthine levels in the active and sedentary groups were -0.97 +/- 1.36 and 0.80 +/- 0.57 micromol/liter, respectively (p < 0.05). This result suggests that mild intensity exercise increases the serum hypoxanthine concentration in the elderly leading inactive daily life, and physical activity suppresses an increase in the serum hypoxanthine levels by mild exercise.

Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia.

Hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) is a common intermediate metabolite of cholesterol synthesis and ketone formation in the liver. In order to study the effect of HMG-CoA reductase inhibitor (pravastatin) on ketone formation, changes in the plasma levels of ketone bodies by treatment with pravastatin were studied in 18 non-insulin dependent diabetics with hypercholesterolemia. Body mass index, diabetic control, and plasma free fatty acid levels were not changed during the study, and the plasma levels of cholesterol decreased significantly from 250 +/- 25 to 211 +/- 34 mg/100 ml after 6 months of pravastatin treatment. The plasma levels of acetoacetic acid also significantly decreased from 37.7 +/- 22.6 to 28.4 +/- 13.4 mumol/l, and those of 3-hydroxybutyric acid and total ketone bodies also tended to decrease after pravastatin treatment. These results suggest that pravastatin decreases ketone formation in hepatic mitochondria besides cholesterol synthesis in hepatic microsome.

Upregulation of Bcl-2 protein in the myasthenic thymus.

We examined the expression of Fas antigen and Bcl-2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic tissue, immunoreactivity for Fas antigen was observed mainly in the network of medullary epithelial cells. In contrast, expression of Fas antigen was rare in the cortex. Fas antigen was also detected to some degree in thymoma tissue from 3 patients. Bcl-2 protein was highly expressed in the medullary thymocytes in the hyperplastic thymic tissue, whereas its staining was quite low in myasthenia gravis thymomas. The number of Bcl-2-positive thymocytes in the medulla was significantly greater in the hyperplastic myasthenia gravis thymic tissue than in the control thymic tissue. These findings suggest that Bcl-2 protein may be upregulated in the myasthenia gravis thymus and that this phenomenon may be related to impaired apoptotic cell death of autoreactive thymocytes in myasthenia gravis.

Reversible MRI and CT findings in uremic encephalopathy.

In this 35-year-old woman with chronic glomerulonephritis and uremic encephalopathy, the basal ganglia bilaterally, internal capsules and periventricular white matter showed hypodensity on CT, low signal intensity on T1-weighted MRI and high signal intensity on T2-weighted MRI. Following a series of dialyses, her clinical symptoms and blood chemistry improved. The CT and MRI returned to normal. These reversible abnormalities may be caused by reversible ischemic change, but disorders of cerebral metabolism and uremic toxins may contribute.

The effects of high-frequency inflation and high-frequency deflation on respiration in rabbits.

High-frequency inflating and deflating triangular pulses of pressure were applied to air in the trachea of urethane-chloralose-anesthetized rabbits. Expiratory time was increased by high-frequency inflation (HFI) and decreased by high-frequency deflation (HFD). Both had little effect on inspiratory time or tidal phrenic nerve activity. HFD provoked more tonic type phrenic activity, with discharges being evident during the expiratory phase. It was demonstrated that HFI, which probably stimulates pulmonary stretch receptors, inhibits the initiation of inspiration and HFD, which probably stimulates irritant receptors, facilitates inspiration.

Thyrotropin-releasing hormone effects on guinea pig antrum.

Thyrotropin-releasing hormone transiently increased resting tension and spontaneous contraction amplitude more potently in longitudinal muscle than in circular muscle. The frequency of the contraction did not change. Excitation was enhanced by eserine, and blocked by atropine and tetrodotoxin; this excitation was, therefore, probably mediated by acetylcholine release from cholinergic neurons in the myenteric plexus. In the presence of atropine, thyrotropin-releasing hormone (10(-10) M) inhibited spontaneous contraction, particularly in longitudinal muscle. This was accompanied by decreased resting tension at and above 10(-8) M. Because contraction was not blocked by adrenergic blockade, indomethacin, methysergide, or hexamethonium, but was abolished by tetrodotoxin, it was postulated that thyrotropin-releasing hormone might stimulate nonadrenergic, noncholinergic inhibitory neurons. There was no cross-tachyphylaxis between 5-hydroxytryptamine and thyrotropin-releasing hormone. Results show that 5-hydroxytryptamine does not interact with thyrotropin-releasing hormone.

Effects of histamine inhalation and airway vibration on phrenic nerve activity in rabbits.

Experiments were performed on 8 rabbits under urethane-chloralose anesthesia. Histamine aerosol (5%) administered into the trachea by a cannula produced tonic activity of the phrenic nerve, with discharges also being evident during the expiratory phase. Airway vibration (100 Hz) inhibited this tonic activity and caused silence during the expiratory phase.

Facilitation of inspiration by intracerebroventricular injection of thyrotropin-releasing hormone in rabbits.

Effects of fourth cerebroventricular injection of thyrotropin-releasing hormone (TRH) on respiration were studied in vagotomized rabbits. Phrenic neural activity was recorded and integrated. TRH (1.0 microgram) injection facilitated phrenic neural activity and increased respiratory rate. Peak phrenic nerve activity increased slightly or showed no apparent changes when tonic activity appeared. Tidal phrenic neural activity either increased or decreased, depending on relations between peak phrenic activity and tonic activity. Results suggest that TRH facilitates central respiratory activity to induce tonic activity and increase respiratory rate.

Endogenous opioid peptide effects on the guinea-pig biliary tract.

The effects of the endogenous opioid peptides, dynorphin (1-13), Met-enkephalin and beta-endorphin, on contraction induced by transmural stimulation of terminal bile duct preparations (terminal cavity and ampulla) and gallbladder were investigated in vitro. These peptides inhibited ampulla contraction, dose dependently. The potency order, indicated by ID50, was the same as in the guinea-pig ileum, but the absolute ID50 values in the ampulla were lower than in the ileum. In the terminal cavity, the dynorphin (1-13) ID50 was still less than in the ampulla, and beta-endorphin and Met-enkephalin did not reduce contraction by as much as 50%. In the gallbladder, the effects of these opioid peptides on contraction induced by transmural stimulation were not significant. The results suggest differences in the receptor populations of the ampulla and terminal cavity, and lack of opiate receptors (at least micro and k receptors) in the gallbladder.

ATPase activity and calcium uptake of microsomes isolated from stomach smooth muscle after exposure to phospholipase C.

ATPase activity and Ca2+ uptake were examined in microsomal membrane fractions isolated from guinea pig stomach smooth muscle which had been exposed to phospholipase C (PLC). Basal Mg2+-ATPase, Na+, K+-ATPase and Ca2+, Mg2+-ATP activities were inhibited in a time dependent manner by PLC treatment. There was positive correlations between each of these ATPase activities and total phospholipid content of the microsomal fraction. Phosphotidylcholine restored Ca2+, Mg2+-ATPase activity of the microsomal fraction isolated from the tissue which had been treated with PLC for 30 min but not after 60 min. Ca2+ uptake in the presence of ATP by microsomal fraction from tissue treated with PLC for 60 min was significantly decreased. The results provide a cellular basis for the inhibitory effect of PLC on contractility of stomach smooth muscle.

Effects of morphine on the guinea-pig biliary tract.

The effects of morphine on the terminal bile duct (terminal cavity and ampulla) and gallbladder were investigated in vitro. Morphine, above 10(-7) M, inhibited spontaneous contraction of the terminal cavity and ampulla. The contraction evoked by transmural stimulation, which was inhibited by atropine and tetrodotoxin, was dose dependently suppressed by morphine above 10(-10) M in the amp]ulla, and above 10(-8) M in the terminal cavity. Morphine did not affect the acetylcholine (ACh)-induced contraction, but reduced the contraction evoked by 5-hydroxytryptamine (5-HT) which was suppressed by atropine. In the gallbladder, morphine did not affect the spontaneous contraction, or the contraction evoked by transmural stimulation, ACh, or 5-HT. The 5-HT-induced contraction was not affected by atropine. The results show that morphine reduces acetylcholine release from cholinergic neurons in the terminal bile duct, but not in the gallbladder. The contraction induced in gallbladder by 5-HT was not mediated by cholinergic neurons.