Yuko Okazaki

Age-related changes of mineral contents in the human aorta and internal thoracic artery

To elucidate accumulations of minerals in the human aorta and internal thoracic artery, their relative contents (RCs) of minerals were analyzed by inductively coupled plasma atomic emission spectrometry.Aortas from 47 men and 24 women subjects were examined. The ages of these subjects ranged from newborn to 99 yr. After the age of 40 yr, RCs of calcium and phosphorus began to increase, and thereafter increased stepwise in the 50s and 70s. In the 70s, their accumulations were markedly increased.Internal thoracic arteries from 16 men and 7 women subjects were examined. These subjects ranged in age from 65–93 yr. It was found that all the RCs of calcium were low, <5.0 mg/g dry wt, and there was no age-dependent increase of calcium contents in internal thoracic arteries.

DIFFERENCE OF MINERAL CONTENTS IN HUMAN INTERVERTEBRAL DISKS AND ITS AGE-RELATED CHANGE

To establish a difference of the relative contents (RCs) of elements among the cervical, thoracic, and lumbar intervertebral disks and its age-related change, the intervertebral disks between the axis and the sacrum, which were resected from the nine cadavers who died at 53 to 99 yr old, were analyzed by inductively coupled atomic plasma emission spectrometry. It was found that both the RCs of calcium and phosphorus were high in the cervical disks, especially the highest in the disk between the 6th and 7th cervical vertebrae, and lower in the order of the cervical, thoracic, and lumbar intervertebral disks. In regard to the RCs of sulfur and magnesium, there were no significant differences among the cervical, thoracic, and lumbar intervertebral disks. In addition, it was found that both the RCs of calcium and phosphorus in the cervical intervertebral disks started to increase in the sixth decade of life, became the highest in the eighth decade of life, and then decreased.

Age-related changes of elements in the human articular disk of the temporomandibular joint

To elucidate compositional changes of the articular disk (AD) of the temporomandibular joint (TMJ) by aging, elements of the ADs resected from 18 cadavers were determined by inductively coupled plasma atomic-emission spectrometry. It was found that calcium contents of ADs in TMJs increased progressively with aging, whereas the sulfur contents of the ADs decreased slightly with aging. Regarding the content of phosphorus, the contents increased progressively with aging. The study revealed that age-related changes of calcium contents in the ADs of TMJs were similar to those in women’s pubic symphyses, but not those in intervertebral disks and menisci.

Age-related changes of elements in human anterior cruciate ligaments and ligamenta capitum femorum

To elucidate compositional changes of human ligaments by aging, the content of elements in anterior cruciate ligaments (ACLs) and ligamenta capitum femorum (LCFs) was analyzed by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 11 men and 7 women, ranging from 59 to 91 yr of age. With regard to the content of elements, the content of sulfur and iron was significantly higher in the LCFs than in the ACLs. It was found in the ACLs that the content of sulfur decreased gradually with aging, whereas the content of calcium, phosphorus, and magnesium increased progressively with aging. On the other hand, it was found in the LCFs that the content of magnesium decreased gradually with aging, whereas the content of phosphorus increased progressively with aging. The common finding that the content of phosphorus increased with aging, but the content of iron decreased, was obtained in the ACL and LCF. Regarding sexual difference, it was found in both the ACLs and LCFs that the content of phosphorus was higher in women’s ligaments than in men’s.

HIGH ACCUMULATION OF CALCIUM AND PHOSPHORUS IN HUMAN ILIAC ARTERIES

To elucidate accumulation of minerals in human iliac arteries with aging, the content of minerals was analyzed by inductively coupled plasma atomic emission spectrometry. Bilateral common, internal, and external iliac arteries of 16 men and 8 women, ranging ages from 65 to 93 yr, were examined. It was found that an extremely high accumulation of calcium and phosphorus occurred in the common iliac artery at old age, being higher than that of the internal and external iliac arteries. It should be noted that the accumulation of calcium and phosphorus is the highest in the common iliac artery among the human arteries examined to date.Regarding sexual differences, the content of calcium and phosphorus in the common and internal iliac arteries was higher in women than in men, whereas their content in the external iliac artery was lower in women than in men.

HIGH ACCUMULATION OF ELEMENTS IN THE HUMAN FEMORAL ARTERY

The relative contents (RCs) of elements in the femoral arteries as well as the thoracic aorta, coronary, basilar, and radial arteries from 26 subjects within the age range between 55 and 92 yr old, were analyzed by inductively coupled plasma atomic emission spectrometry.The RCs of calcium and phosphorus in the femoral arteries started to increase before the age of 60 yr. The RCs of magnesium increased after the age of 70 yr. However, the RCs of sulfur did not change significantly within the age range between 55 and 92 yr.With regard to localization of the mineral accumulations in the femoral arterial wall, it was found that the accumulations of calcium and phosphorus occurred only in the tunica media, only in the tunica intima, or in both the tunica media and the tunica intima. The manner of accumulation of calcium and phosphorus in the femoral arterial wall was different from that in the aortic wall.The average RCs of calcium in the 26 specimens were the highest in the femoral artery, followed in descending order by the thoracic aorta, coronary, basilar, and radial arteries. The average RCs of phosphorus were highest in the thoracic aorta, followed by the coronary, femoral, basilar, and radial arteries. It is noted that the accumulation of mineral elements never occurred uniformly in all the arteries.

Penetration of cisplatin into mouse brain by lipopolysaccharide

We investigated the penetration of cisplatin into the mouse cerebral cortex-rich region (CCR) induced by lipopolysaccharide (LPS). With the injection of cisplatin into mice 3 h after the LPS treatment, platinum was detected in the CCR during the 7 days after the injection, while platinum was not detected in the CCR of cisplatin-injected mice without LPS pretreatment and of mice simultaneous treated with cisplatin and LPS. The N(G)-nitro-L-arginine methyl ester dose-dependently lowered the platinum level. A dose of 5 mg/kg of aminoguanidine reduced the increase in the platinum level of the LPS-treated mouse, and platinum was no longer detected at doses of 20 mg/kg in the aminoguanidine-injected group. At doses of 500 mg/kg aminoguanidine, however, no effect was seen on the platinum level of the CCR induced by LPS. Regarding indomethacin, the injection of 5 mg/kg resulted in a decrease in the platinum content of the CCR, but not undetectable level. These results suggest that LPS increases the penetration of cisplatin into the mouse brain, and platinum may be accumulated in the CCR. Nitric oxide and prostaglandins contribute to the penetration of platinum into the cerebral cortex.

Zinc deficiency exaggerates diabetic osteoporosis

Streptozotocin diabetic rats showed an increase of bone fragility (11.9 +/- 2.1 kg/cm2 vs. 16.8 +/- 2.0, P < 0.005) which was normalized by insulin treatment (18.3 +/- 4.2), indicating that osteoporosis was induced in diabetic rats. The rats were fed a zinc-deficient diet (0.16 mg/100 g) or a control diet (5.2 mg/100 g). This mild zinc-deficient diet did not lower the serum zinc level. The cortical bone of diabetic rats was shown to be markedly thinner by microscopic examination of ground cross-sections of the tibia. Zinc deficiency induced a reduction in the calcium content of diabetic bone when compared with the rats on a control diet. Urinary excretion of calcium and phosphorus was significantly increased in diabetic rats, and increased further when the rats were fed a zinc-deficient diet. Moreover. the bone calcium and phosphorus concentrations were significantly lower in these animals. These changes in the zinc-deficiency rats were not reversed by insulin treatment. Our findings suggest that osteoporosis in the diabetic rats was due to thinning of the bone cortex secondary to mineral loss and can be reversed by insulin treatment, and that these skeletal changes are greatly enhanced by mild zinc deficiency. In addition the effects of zinc deficiency cannot be completely reversed by insulin treatment.

High accumulation of minerals in the human arteries of lower limb

To elucidate accumulation of minerals in the human arteries, the relative contents (RCs) of minerals in the arteries of the upper and lower limbs were analyzed by inductively coupled plasma atomic emission spectrometry.It was found that the RCs of calcium and phosphorus in the femoral and popliteal arteries of the lower limb increased with aging, whereas those in the axillary and radial arteries of the upper limb did not increase with aging. This result indicates that higher accumulation of calcium and phosphorus occurs in the arteries of the lower limb with aging as compared with that in the arteries of the upper limb, and the prevalence of arteriosclerosis increases in the arteries of the lower limb with aging but not in the arteries of the upper limb.

Roles of nitric oxide and prostaglandins in the increased permeability of the blood-brain barrier caused by lipopolysaccharide.

We investigated the involvement of nitric oxide (NO) and prostaglandins (PGs) in the damage to the blood-brain barrier (BBB) induced by lipopolysaccharide (LPS), using fluorescein as a tracer in mice. Aminoguanidine, a competitive inhibitor of inducible NO synthase (iNOS), when administered s.c. at 5 mg/kg, but not 500 mg/kg, reduced significantly the increase in brain fluorescein level after its i.v. injection in LPS-treated mice. When 1000 mg/kg of l-arginine, a substrate of NOS, were co-administered with 5 mg/kg of aminoguanidine to LPS-treated mice, the inhibitory effect of aminoguanidine on the increased fluorescein level disappeared. N(G)-Nitro-l-arginine methyl ester (l-NAME), a non-isoenzyme-selective NOS inhibitor, when administered s.c. at 5 mg/kg, only slightly reduced the LPS-induced increase in the brain fluorescein level. A pretreatment with dexamethasone, which suppressed the induction of both iNOS and cyclooxygenase 2 (COX-2), tended to decrease the brain fluorescein level in LPS-treated mice. Indomethacin, a COX inhibitor, at 5 mg/kg, but not 10 mg/kg, suppressed significantly the LPS-induced increase in the brain fluorescein level. These results involve that both the NO produced by iNOS and the PGs produced by COX contribute to enhance BBB permeability in LPS-administered mice.