The effect on the bones of condensed phosphate when used as food additives: Its Importance in Relation to Preventive Medicine

Based on the fact that chemical products such as binding agents are produced by mixing three kinds of phosphates with different ratios, we mixed metaphosphate, polyphosphate and pyrophosphate. Each was made to Na-phosphate, K-phosphate, and Ca-phosphate and each was mixed with commercial feeds so that the content of P would be approximately 0.1, 0.15, 0.3, 0.4, 0.6 and 1.0%. The prepared pellets were given to ICR, CF # 1 and AKR strains of mice at 29 days of age for 680 days and observations were made through this experimental period at different stages. The observations were also carried out on the mice administered with the experimental feeds for 1.5 months from 9 to 10.5 months of age. The observations were compared with those of the control group at all times. As a result, plasma 1 α, 25 (OH)₂ D₃ and P levels were always significantly higher in the phosphate administered groups relative to the control. Urine P and Fe increased while urine Ca decreased in the phosphate-treated groups. The effect of phosphates on the bones was studied taking soft X-ray pictures of hind legs and applying microdensitometry to them. Through these observations we recognized thinning of the cortex of bones, reduction of marrow trabecules and development of osteophyte. Histological observations disclosed that changes in knee joint tissues were apparent; that is, a decrease in or an irregular loss of the number of cells in superficial, intermediate, and radial strata of the joint cartilage, proliferation of subchondral bone, and the development of osteophytes were noted. As for muscles, diameters of musclar fibers became smaller; in particular, type II fibers showed greater shrinkage. Regarding kidneys, swelling and atrophy of glomerular capillaries, proliferation of mesangial cells, nephroselerosis, swelling, thinning, and loss of tubular epithelium, interstitial tissue inflammation, development of cylindruria, and deposition of calcium were observed. All these changes seem to be a particularly advanced aspect of the changes which are more pronounced with increasing dose and age. These changes were found even in the group administered with the feed containing 0.1% phosphorus, and, these changes were dependent on the concentration level of P. It was observed that administration to older subjects for a short term (1.5 months) produced effects stronger than those to younger subjects administered for a long term (10.5 months). The effects of condensed Ca-phosphate on bones were similar to those of condensed Na- and K-phosphates, and, hence, it was supposed that these effects were caused by phosphate radicals. An erratum to this article is available at .     

Antitumor effects of oral administration of an interferon-inducing pyrimidinone,Bropirimine, on murine renal-cell carcinoma

Bropirimine [2-amino-5-bromo-6-phenyl-4-(3H)-pyrimidinone] is a low-molecular-weight compound that acts as an inducer of interferon in several animal species. Experiments were designed to explore the possibility of using this drug for the treatment of renal-cell carcinoma (RCC). Euthymic BALB/c mice were inoculated with murine RCC (Renca) cells and given graded doses of Bropirimine p.o. for 5 consecutive days beginning on day 1 following tumor inoculation. These mice were killed and tumors were excised on day 21. Bropirimine significantly (P<0.01) inhibited the tumor growth at a daily dose of 1,000 or 2,000 mg/kg. No adverse effect or toxicity was noted at 1,000 mg/kg, and at 2,000 mg/kg there was only a marginal body-weight reduction without any other appreciable side effect. In addition to the inhibition of tumor growth, there was a small yet significant (P<0.05) increase in the duration of survival (in days) in the Bropirimine-treated animals. When the treatment was delayed to begin on day 6 following tumor inoculation, Bropirimine did not suppress tumor growth in euthymic mice, pointing to the importance of the timing of the treatment. In athymic nude BALB/c mice lacking T-cells or T-cell function, Bropirimine also inhibited tumor growth (P<0.01). The antitumor effect of this drug was abolished by pretreatment with anti-asialo GM1 serum, which eliminated natural killer (NK) activity in euthymic mice. In vivo treatment with Bropirimine augmented the cytotoxicity of lymphocytes isolated from the spleens or lungs of the tumor-bearing mice, which were active against Renca and YAC-1 cells in vitro. This activity was NK-cell-dependent as judged on the basis of the results of the in vitro complement-dependent cytotoxicity assay. Since Bropirimine induced interferon (IFN)-/ production, significantly (P<0.05) elevating its serum concentration, and since this drug mimics the effects of IFN-/, it seemed likely that the Bropirimine-induced NK cell augmentation we found was mediated by IFN-/. These results suggest that Bropirimine, a booster of NK activity, may have potential as an adjunct to other therapeutic modalities in the treatment of human RCC.     

Simultaneous assessment of right ventricular function and hypertrophy by Tc-99m MIBI

PURPOSE: Tc-99m MIBI allows the simultaneous performance of cardiac blood pool scintigraphy and myocardial SPECT. The authors performed studies to determine whether right ventricular function and hypertrophy can be evaluated simultaneously using Tc-99m MIBI in patients with right heart disease. METHODS: Using right heart catheterization, several parameters of pulmonary circulation were measured, including right ventricular ejection fraction, in 23 patients with chronic pulmonary disease and pulmonary vascular disease. Within 1 week, right heart blood pool scintigraphy was performed using the first-pass method using Tc-99m MIBI. The right ventricular ejection fraction calculated from right heart blood pool scintigraphy was compared with that measured using right heart catheterization. Myocardial SPECT was performed 1 hour after right heart blood pool scintigraphy. On the short axis images, which allowed optimal visualization of the right ventricle, the right and left ventricular free walls were established as regions of interest. Myocardial wall counts were determined. The right ventricular uptake: left ventricular uptake ratio was calculated to study the relation of that ratio to mean pulmonary artery pressure and total pulmonary resistance. RESULTS: A significant correlation was observed between the right ventricular ejection fraction calculated on right heart catheterization and that calculated on right heart blood pool scintigraphy. The right ventricular uptake:left ventricular uptake ratio correlated positively with pulmonary artery pressure and total pulmonary resistance. CONCLUSION: These results suggest that Tc-99m MIBI allows simultaneous noninvasive evaluation of cardiac function and structure, which previously was considered impossible in patients with right heart disease.     

Diaphragm reconstruction with autologous fascia lata: Report of a case

When the diaphragm is excised so wiely that the defect cannot be closed directly during an operation on either thoracic or epigastric tumors, a reconstruction of the defect is necessary. We used harvested autologous fascia lata to reconstruct the diaphragm in a patient undergoing a pleuropneumonectomy with a partial diaphragmatic resection for malignant mesothelioma.     

Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)₂ reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1.     

Bright light treatment for night-time insomnia and daytime sleepiness in elderly people: comparison with a short-acting hypnotic

Night-time bright light (BL) treatment and triazolam (0.125 mg/day) were given to three healthy elderly people in a cross-over design. They kept a daytime sleepiness test and a sleep log, and their wrist-activity was monitored simultaneously. Subjectively, BL increased daytime sleepiness and naps, and decreased night-time sleep. Triazolam decreased daytime sleepiness and naps, and increased night-time sleep. Actigraphic night-time sleep and naps on the first day were similar to these results. However, on the fourth day night-time insomnia induced by BL had recovered, and naps were shorter than the baseline. Triazolam increased actigraphic naps as the days passed.     

Association analysis of the GABA(A) receptor subunit genes cluster on 5q33-34 and alcohol dependence in a Japanese population

Recent investigations suggest that genetic susceptibility to alcohol dependence may be conferred by GABA(A) receptor subunit genes. In this study, three RFLPs at the GABA(A)beta2, GABAAalpha6, GABA(A)alpha1 and two at the GABA(A)gamma2 receptor subunit genes, were examined for association with alcohol dependence in 189 subjects meeting DSM-III-R criteria for this disorder and 152 unrelated controls from a Japanese population. The results demonstrated no association between the AlwNI RFLP at the GABA(A)alpha6 receptor subunit gene and alcohol dependence (P = 0.059). However, the NciI RFLP at the GABA(A)gamma2 receptor subunit gene was associated with alcohol dependence comorbid with antisocial personality disorder (P = 0.021). This supports a recent finding reporting an association between the GABA(A)gamma2 receptor subunit gene and alcohol dependence with criminal record in a Finnish population. Taking into account the effects of multiple comparisons, this result should be interpreted with caution pending replication.     

Factors influencing joint-preserving operations in the treatment of the late stages of osteoarthritis of the hip

Between November 1983 and December 1992, 136 hips (119 patients) with coxarthritis were operated on using joint-preserving techniques based on the rationale of Pauwels' osteotomy. The criterion for selection was a patient in whom the height of the joint space in the weight-bearing area of the hip was less than 1 mm. The mean age at operation was 48 years and the mean follow-up 109 months (60 to 171). Hips were categorised using Bombelli's classification of osteoarthritis, into atrophic and non-atrophic types. The endpoint was defined as that at which the height of the joint space became less than 1 mm again. The Kaplan-Meier curve showed that the rate of survival of the non-atrophic group was significantly better than that of the atrophic group. Cox's proportional hazard model indicated that the factors influencing the results of joint-preserving operations included Bombelli's classification, postoperative incongruence of the joint and the height of the joint space.