Simultaneous accumulation of calcium, phosphorus, and magnesium in various human arteries.

To elucidate compositional changes of the arteries with aging, the authors investigated the relationships among average contents of calcium, phosphorus, sulfur, and magnesium in the arteries by inductively coupled plasma-atomic emission spectrometry. The arteries used were the thoracic and abdominal aortas, coronary, common carotid, anterior, middle and posterior cerebral, vertebral, basilar, internal thoracic, axillary, radial, truncus celiacus, common, internal and external iliac, femoral, popliteal, and umbilical arteries. It was found that high correlations were found between the average contents of calcium and phosphorus, between the average contents of calcium and magnesium, and between the average contents of phosphorus and magnesium in the arteries, but not between the average contents of sulfur and the other elements. These correlations revealed that as the content of calcium and phosphorus increased in the arteries, the magnesium content increased simultaneously in the arteries, but the sulfur content did not. It is likely that magnesium forms compounds with phosphorus in the arteries.

Accumulation of calcium and phosphorus accompanied by increase of magnesium and decrease of sulfur in human arteries.

To elucidate the accumulation of elements in the arteries with aging, the authors investigated age-related changes of elements in human arteries, such as the thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 17 men and 9 women, ranging in age from 55 to 92 yr in the cases of the five arteries, except for the common iliac arteries, in which the subjects consisted of 16 men and 8 women, ranging in age from 65 to 93 yr. It was found that there were significantly direct correlations between calcium and phosphorus contents and between calcium and magnesium contents in all of the six arteries: thoracic aorta, femoral, basilar, coronary, radial, and common iliac arteries. Significantly direct correlations were also found between phosphorus and magnesium contents in the five arteries, except for the basilar artery. In contrast, significantly inverse correlations were found between calcium and sulfur contents and between phosphorus and sulfur contents in the four arteries, except for the coronary and radial arteries. These revealed that the accumulation of calcium and phosphorus in the arteries was accompanied by an increase of magnesium in the arteries and by a decrease of sulfur in the arteries.

Calcium and phosphorus in aged human cerebral arteries.

To elucidate the compositional changes of the cerebral arteries with aging, the authors investigated age-related changes of the calcium and phosphorus contents in the cerebral arteries by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 11 men and 5 women, ranging in age from 52 to 96 yr. The anterior, middle, and posterior cerebral arteries derived from the same subjects were used in the present study. It was found that there were no significant relationships between age and calcium or phosphorus content in the anterior, middle, and posterior cerebral arteries, indicating that the accumulation of calcium and phosphorus scarcely occurred in the anterior, middle, and posterior cerebral arteries with aging. It was examined whether there were relationships in the calcium and phosphorus contents among the anterior, middle, and posterior cerebral arteries, It was found that there was a significant relationship in both the contents of calcium and phosphorus between the middle and posterior cerebral arteries, but not between the anterior and middle cerebral arteries nor between the anterior and posterior cerebral arteries.

Increases of calcium and magnesium and decreases of phosphorus and iron with aging in human uterine tubes.

To elucidate compositional changes of the uterine tube by aging, the authors studied age-related changes of elements in human uterine tubes by inductively coupled plasma-atomic emission spectrometry. The uterine tubes were resected postmortem or surgically removed from patients with uterine myoma. It was found that the contents of calcium and magnesium increased progressively with aging in uterine tubes, whereas the contents of phosphorus and iron decreased gradually with aging. The sulfur content of uterine tubes remained constant and independent of aging. Regarding relationships between elements, significant relationships were found between calcium and magnesium contents, between phosphorus and iron contents, between phosphorus and sulfur contents, and between phosphorus and sodium contents in human uterine tubes.

Relationship between meniscal degeneration and element contents.

The purpose of this study is to investigate the relationship between meniscal degeneration and element contents. The contents of elements (calcium, phosphorus, sulfur, and magnesium) in the menisci from 17 patients with osteoarthritis (OA) of the knee, 6 with rheumatoid arthritis (RA), and 2 who underwent the surgical operation for malignant tumors (control) were analyzed by inductively coupled plasma-atomic emission spectrometry, and the menisci were divided into four stages (Stage 0-3) of histological degeneration. The calcium contents of the menisci were 0.26 +/- 0.16 in Stage 0, 0.50 +/- 0.37 in Stage 1, and 0.69 +/- 0.66 in Stage 2, respectively (the values represent mg elements/g dry tissue). They increased with the progression of the stage. This tendency was found in the menisci with OA, but was not clear in those with RA. The calcium content in the control group was 0.17 +/- 0.09 mg/g. There was no significant relationship between the stage of degeneration and the contents of phosphorus, sulfur, or magnesium. The calcium content of the meniscus might indicate the degree of meniscal degeneration.

Selective accumulations of aluminum in five human arteries.

The aim of the present study was to determine variability of aluminum (Al) accumulation in human arteries and to observe the relationship between Al and five other elements (Ca, Fe, Mg, P, and Si) in the arteries. The Al contents in the thoracic aorta, basilar, coronary, femoral, and radial arteries of 26 human subjects were estimated by an inductively coupled plasma-atomic emission spectrometer and compared quantitatively to five elements. Al was detected in 88% of the cases in both the femoral and radial arteries, 73% in the coronary artery, 58% in the aorta, and 31% in the basilar artery. The average Al content was highest in the femoral artery (48.3 +/- 15.0 microg/g dry weight) and lowest in the basilar artery (8.1 +/- 3.6 microg/g). The Al had positive correlations with P, Ca, or Mg in both the aorta and femoral artery, and with Ca or P in the basilar artery. In the coronary artery, a correlation was found between Al and Si. No relationships were found between Al and each of the five elements in the radial artery. From these results, Al varied widely among the five arteries and accumulated more in the femoral and radial arteries but less in the basilar artery. These accumulations of Al were positively correlated with Ca or P in several arteries, but not sufficiently to explain the accumulation of Al. Further investigations are required to understand the mechanism of the variability of Al accumulation in the arteries.

[The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica (Ephedraceae))].

We investigated false-positive reactions obtained from a drug screening test using a Triage panel. We detected 2 cases giving false-positive reaction for AMP (amphetamine, methamphetamine) during the screening of 187 normal subjects. Subsequent follow up testing by high-performance liquid chromatography (HPLC), showed both to be false-positive reactions. As both cases have a history of ingesting the herbal drug, Ma-huang (Ephedra sinica (Ephedraceae)), containing ephedrine, we examined the relationship between false-positive reactions on Triage and Ma-huang. All urine samples collected from 7 healthy volunteers following administration of Ma-huang indicated AMP positive on Triage. Also a high ratio of AMP positives was observed in the patients who were administered Ma-huang-containing drugs at the hospital. However, none of them were identified as true-positives by HPLC or gas chromatography mass spectrometry (GC/MS) analysis. The extract of Ma-huang contained in herbal drugs, which otherwise contain neither amphetamine nor its derivatives, gives (AMP) positive indications on Triage. We speculate that unidentified components of Ma-huang cause the false-positive reactions. We suggest that follow-up tests by GC/MS or HPLC are needed wherever a positive result is obtained from a screening test by Triage. Furthermore, it will be established to continue collecting information on prescribed and non-prescribed drugs.

Relationships among element contents in the intimal, middle, and external tunicae of the thoracic aorta.

To examine an accumulation of elements within the arteries with aging, the authors investigated the element contents in the intimal, middle, and external tunicae of the thoracic aorta. The subjects consisted of six men and four women, ranging in age from 57 to 99 yr. The wall of the thoracic aorta was separated into the intimal, middle, and external tunicae by scrubbing the wall of the thoracic aorta with an edge of slide glass and the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were significant relationships among calcium, phosphorus, magnesium, sulfur, and sodium in both the intimal and middle tunicae of the aorta, but not in the external tunica. These results revealed that no significant differences were found in element compositions of deposits between the intimal and middle tunicae.

Simultaneous accumulation of magnesium with calcium and phosphorus in aorta and iliac arteries of Thai.

To elucidate compositional changes of arteries with aging, the authors previously investigated age-related changes of mineral contents in the various arteries of Japanese and Japanese monkey. To examine whether there were differences between races in regard to age-related changes of mineral contents and the relationships among element contents in the arteries, the authors investigated the arteries of Thai. The subjects consisted of 13 men and 3 women, ranging in age from 39 to 84 yr. After the ordinary dissection at Chiang Mai University was finished, abdominal aortas, common iliac, internal iliac, and external iliac arteries were resected and the element contents were determined by inductively coupled plasma-atomic emission spectrometry. The contents of calcium, phosphorus, and magnesium became the highest in the fifties in the abdominal aorta, common iliac, and external iliac arteries, whereas the contents of calcium and magnesium became the highest in the sixties in the internal iliac artery, and decreased thereafter. In regard to relationships among element contents, it was found that there were high correlations between calcium and phosphorus contents, between calcium and magnesium contents, and between phosphorus and magnesium in all of the abdominal aortas and three iliac arteries. The mass ratios of magnesium to calcium and phosphorus were each similar in the abdominal aorta, common iliac, and internal iliac arteries, except for the external iliac artery, in which it was slightly high. These revealed that as calcium and phosphorus increased in the arteries with aging, magnesium increased in the arteries as well. The differences between the arteries of Thai and Japanese were discussed in the present article.

Quantitative changes of calcium, phosphorus, and magnesium in common iliac arteries with aging.

To elucidate the mechanism of element accumulations in the arteries with aging, the authors investigated the mass ratios among calcium, phosphorus, and magnesium in the common iliac arteries by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 16 men and 8 women, ranging in age from 65 to 93 yr. It was found that there were extremely significant correlations between calcium and phosphorus contents, between calcium and magnesium contents, and between phosphorus and magnesium contents in the common iliac arteries. In regard to the mass ratio, although the mass ratio of calcium to phosphorus was almost constant, the mass ratios of magnesium to calcium and phosphorus were different at early and advanced stages of the accumulation of calcium and phosphorus. It was found that both the mass ratios of magnesium to calcium and phosphorus were higher at an early stage of the accumulation of calcium and phosphorus in the arteries than at an advanced stage of the accumulation.

Accumulation of magnesium as well as calcium and phosphorus in Japanese monkey arteries with aging.

To examine whether an accumulation of elements in the arteries with aging differs between human and animal, the authors investigated the relationships among element contents in the arteries of the Japanese monkeys. The Japanese monkeys consisted of five males and four females, ranging in age from 2 to 29 yr. The aorta, common and external iliac, femoral, common carotid, subclavian, and axillary arteries were resected from the monkeys and element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were very high correlations between calcium and phosphorus contents, between calcium and magnesium contents, and between phosphorus and magnesium contents in all of the monkey arteries. In addition, significant correlations were found among the other element contents in some, but not all of the arteries. These results were consistent with the foregoing findings of the human arteries. It is likely that magnesium forms compounds with phosphorus or calcium in the monkey arteries.

Age-dependent changes of elements in human trachea.

To elucidate compositional changes of human trachea by aging, element contents in tracheae were determined by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The sulfur content of the tracheae decreased gradually with aging. In regard to calcium and phosphorus, both the contents increased to about threefold amounts in their seventies compared with those in their sixties, and decreased thereafter. The contents of calcium and phosphorus were the highest in their seventies. Therefore, it is likely that surplus calcium released from bones is deposited temporally in the trachea, and the deposits are released from the trachea at older age. Based on our results of human cartilages, there are two types in regard to calcium accumulation: The first type is that calcium accumulation occurs progressively with aging; the second one is that calcium accumulation becomes the highest in the seventies or eighties, and decreases thereafter. Therefore, the trachea belongs to the second type. Furthermore, the magnesium content remained constant through the age range.

Accumulation of calcium and phosphorus in the mitral valve in comparison with the abdominal aorta and the scaphoid bone.

To clarify why calcification of the mitral valve occurred, the authors chose the abdominal aorta and the scaphoid bone among many arteries and bones, and they studied both relationships in element contents between the mitral valve and the abdominal aorta and between the mitral valve and the scaphoid bone. The subjects consisted of 11 men and 8 women, ranging in age from 52 to 96 yr. The accumulation of calcium and phosphorus occurred progressively with aging in the mitral valve, whereas it became the highest in the sixties in the abdominal aorta and did not increase thereafter. The accumulation of calcium and phosphorus occurred in the abdominal aorta earlier than the thoracic aorta, in which it became remarkable in the seventies. It should be noted that in regard to the accumulation of calcium and phosphorus, no significant correlations were found between the mitral valve and the abdominal aorta. It is suggested that calcification of the abdominal aorta is not essentially accompanied by calcification of the mitral valve. The scaphoid bone was chosen among many bones consisting mainly of spongy bone and the relationship was examined between the calcium content in the mitral valve and the bone mineral density of the scaphoid bone. It was found that there was a low relationship between them. Therefore, it is suggested that a part of the surplus calcium released from bones is deposited in the mitral valve.

Cancer chemopreventive agents, labdane diterpenoids from the stem bark of Thuja standishii (Gord.) Carr.

Seven labdane-type diterpenoids from the stem bark of Thuja standishii (Gord.) Carr. (Cupressaceae) and their analogues showed strong inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among these compounds, 15,16-bisnor-13-oxolabda-8(17), 11E-dien-19-oic acid was revealed to have the strongest inhibitory effect on the EBV-EA activation, being stronger than that of beta-carotene which has been intensively studied in cancer prevention using animal models. 15,16-bisnor-13-Oxolabda-8(17), 11E-dien-19-oic acid was also found to exhibit the excellent anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

Age-dependent decreases of phosphorus and magnesium in human Achilles' tendons.

To elucidate changes of human tendons with aging, the authors studied age-related changes of elements in human Achilles' tendons by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. It was found that the content of calcium increased progressively with aging in the Achilles' tendons, whereas the contents of phosphorus and magnesium decreased gradually with aging. The previous investigations demonstrated that the content of calcium and phosphorus increased progressively with aging in most, but not all, human tissues, except for the bones. In ligaments, such as the anterior cruciate ligament and the ligament of the head of the femur, which are histologically similar to the Achilles' tendon, it was previously found that both the contents of calcium and phosphorus increased with aging in the ligaments. It should be noted that the content of phosphorus in the Achilles' tendons decreased during the aging process. In addition, it was found that there was a very high direct correlation between phosphorus and magnesium contents in the tendons, but not between calcium and phosphorus contents.

Characterization of nociceptin/orphanin FQ-induced pain responses in conscious mice: neonatal capsaicin treatment and N-methyl-D-aspartate receptor GluRepsilon subunit knockout mice.

Activation of primary afferent C fibers gives rise to spinal release of substance P and glutamate, and these mediators facilitate the cascade of nociceptive processing. We recently showed that intrathecal administration of nociceptin or orphanin FQ (hereafter called nociceptin) induced hyperalgesia to noxious thermal stimuli and allodynia to innocuous tactile stimuli applied to conscious mice. In the present study, we designed experiments to elucidate the pathways and mediators of nociceptin-evoked pain responses. Neonatal capsaicin treatment eliminated the induction of hyperalgesia and allodynia by nociceptin. Whereas this treatment markedly reduced the content of substance P in the spinal cord, it did not affect the nociceptin content or the expression of nociceptin receptors and GluRvarepsilon and GluRzeta subunits of N-methyl-D-aspartate receptors in it. The substance P antagonists CP96,345 and CP99,994 blocked the nociceptin-induced hyperalgesia, but not the allodynia. In contrast, the nociceptin-evoked allodynia, but not hyperalgesia, disappeared in N-methyl-D-aspartate receptor GluRvarepsilon1 subunit knockout mice. Both nociceptin-evoked hyperalgesia and allodynia were attenuated by morphine in a dose-dependent manner. Taken together, these results demonstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nociceptin, but in different pathways; the former is mediated by substance P and the latter is mediated by glutamate through the N-methyl-D-aspartate receptor comprising the GluRvarepsilon1 subunit.

Tea catechins and related polyphenols as anti-cancer agents.

Epigallocatechin gallate (EGCg) and theaflavins, a major constituent of green tea infusion and the constituents of black tea, respectively, were found to inhibit matrix metalloproteinases (MMPs) which are intimately associated with tumor invasion and metastasis. EGCg and related polyphenols exhibited apoptosis-inducing activity for several cancer cell lines including human stomach and colon cancer cells. Comparison of the activity of these compounds revealed the importance of the number and the steric disposition of hydroxyl groups. A pyrogallol-type structure in a molecule is a minimum requirement for apoptosis induction of catechin compounds and that in the B ring has an important role in the activity. These data would provide useful information for designing anti-cancer agents on the basis of anti-inhibitory activity for MMPs and/or apoptosis-inducing activity.

Differences in the mineral contents between falx cerebri and tentorium cerebelli.

To elucidate age-related changes of the dura mater, the authors investigated age-related changes of mineral contents in the falx cerebri and the tentorium cerebelli by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The contents of calcium, phosphorus, and magnesium increased progressively with aging in the falx cerebri, whereas the contents of sulfur, iron, and zinc remained constant, being independent of age. In regard to the tentorium cerebelli, the contents of calcium, phosphorus, and magnesium seemed to increase progressively with aging, but the contents of sulfur, iron, and zinc hardly changed with aging. It was noteworthy that there were no significant relationships between the falx cerebri and the tentorium cerebelli in such element contents as calcium, phosphorus, magnesium, sulfur, iron, and zinc.

[Management after hepatectomy of colorectal cancer metastases to the liver--intrahepatic arterial infusion chemotherapy and repeated hepatectomy].

Before Dec. 1993, we resected 17 patients with hepatic metastases from colorectal cancer. Hepatic recurrences developed in 82% patients who had been given mitomycin C or doxorubicin by hepatic-artery. The one-, 3- and 5-year survival rate after surgery was, 88%, 18% and 12%, respectively. Therefore, some new types of adjuvant therapy were needed to improve survival after surgery. This is a retrospective study to determine whether preventive intrahepatic artery infusion chemotherapy (HAI) and repeated hepatectomy are of benefit for patients with hepatic metastases from colorectal cancer who underwent hepatectomy. Thirty-five patients with hepatic metastases from colorectal cancer underwent hepatectomy and were administered 1,500 mg of 5-FU 10 times via the hepatic artery for 5 hrs every 1-2 weeks to prevent hepatic recurrence after Jan. 1994. Nine patients underwent repeated hepatectomy, then HAL following the operation. Non-resectable recurrence were treated by HAI. The amounts of the infused 5-FU dose were 8.5-46.5 g (mean 23 g) and 17-31 times HAI (mean 22 times). Survival rates were 81, 67, 67% and 24%, respectively, after 1, 2, 3 and 4 years. Hepatic disease-free interval rates were 49.3% and 32.5%, respectively, after 1 and 2 years. Preventive HAI could not control hepatic recurrence but prognosis after hepatectomy was improved by these modalities compared with treatment before Dec. 1993. Survival rates of 9 patients who underwent repeated hepatectomy were 89, 89% and 37%, respectively, after 1, 3 and 4 years. The prognosis of patients with hepatic metastases from colorectal cancer was improved by HAI and repeated hepatectomy, but further studies should be undertaken to improve preventive HAI.

Age-related changes of element contents in human mitral and tricuspid valves.

To examine age-related changes of human cardiac valves, mitral and tricuspid valves were analyzed by inductively coupled plasma-atomic emission spectrometry. The subjects for mitral valves consisted of 12 men and 8 women, ranging in age from 52 to 96 yr. The subjects for tricuspid valves consisted of 11 men and 6 women, ranging in age from 52 to 93 yr. Furthermore, 16 of the samples of the cardiac valves were derived from the same subjects. The contents of calcium, phosphorus, and magnesium in the mitral valves increased progressively with advancing age and reached maximum in the 80s in regard to calcium and phosphorus and maximum in the 90s in regard to magnesium. The maximum average amounts corresponded to about three times the average contents in the 60s. In contrast, the content of sulfur in the mitral valves remained constant between the 50s and 90s. Regarding tricuspid valve, the contents of calcium, phosphorus, and magnesium scarcely increased with advancing age, except for one subject who died of chronic renal failure. Histological observations of the mitral valves revealed that deposits of calcium were present in both the elastic fibers and its degenerative tissues of the mitral valve. The present study indicates that the accumulation of calcium, phosphorus, and magnesium occurs progressively in the mitral valve with aging, but does not occur in the tricuspid valve.