Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women.

UNLABELLED: Effect of milk basic protein on bone metabolism in healthy young women. INTRODUCTION: Milk has more beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The object of this study was to examine the effect of MBP on the bone mineral density and bone metabolism of healthy young women. METHODS: Thirty-five healthy young women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for 6 months. The bone mineral density (BMD) of the lumbar vertebrae L2-L4 of each subject was measured by dual-energy X-ray absorptiometry (DXA) at 0 and 6 months of treatment. Serum and urine indexes of bone metabolism were measured at 0, 3 and 6 months. All subjects completed the study in accordance with the protocol. RESULTS: The mean rate of gain of lumbar BMD in the MBP group (1.57%) was significantly higher than in the placebo group (0.13%, P=0.042). When compared with the placebo group, urinary cross-linked N-telopeptides of type-I collagen (NTx) were significantly decreased, and serum osteocalcin was significantly increased in the MBP group at 6 months. CONCLUSION: These results suggested that MBP supplementation was effective in increasing BMD in young women and that this increase in BMD may be primarily mediated through the promotion of bone formation and inhibition of bone resorption by MBP supplementation.

Prolongation of activation-recovery interval over a preexcited region before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Preexisting changes in repolarization properties play an important role in T wave abnormalities (cardiac memory) after ablation in patients with Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct evidence for prolongation of action potential duration (APD) over a preexcited region before and after ablation. METHODS AND RESULTS: We studied 10 patients with ventricular preexcitation due to a left-sided accessory pathway (AP) (group M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation of APD using activation-recovery intervals (ARIs) from epicardial and endocardial unipolar electrograms in patients with WPW syndrome. ARI was calculated from unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before ablation, ARIs at the AP site were significantly longer in group M than in group C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After ablation, group M showed no significant changes in ARIs at the AP and His bundle (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We found by direct analysis of ARIs from the epicardium that APD prolongation over the preexcited region was present before catheter ablation and persisted after catheter ablation. The gradual changes in repolarization properties, including APD prolongation after discontinuation of AP, may be one mechanism of cardiac memory after catheter ablation in patients with WPW syndrome.

The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors.

Angiotensin 1-7 has been recently claimed the active member of the angiotensins' family. In the present study we compared the effect of angiotensin II and angiotensin 1-7 on the concentration of dopamine, serotonin, epinephrine, and norepinephrine and some of their metabolites in the rat hypothalamus, where the levels of angiotensins are particularly high. Intracerebroventricular injection of angiotensin II, but not angiotensin 1-7, time-dependently elevated the levels of both epinephrine (p < 0.05) and norepinephrine (p < 0.05) in the hypothalamus and both effects could be prevented by intracerebroventricular injection of either AT(1) (candesartan), AT(2) (PD123319) or AT(1-7) (A-779) receptor antagonist. Neither angiotensin II nor angiotensin 1-7 produced any changes in the level of dopamine, dihydroxyphenylacetic acid, homovanilic acid, serotonin, 5-hydroxyindoleacetic acid, or tryptophan at any time point in comparison with the control groups. However, AT(1) but not AT(2) receptor blockade, unmasked the stimulatory effect of angiotensin 1-7 on dopamine concentration in the hypothalamus. Thus, angiotensin II and its active metabolite angiotensin 1-7 regulate selectively, albeit differentially, adrenergic, noradrenergic and dopaminergic systems in the hypothalamus, the effects that involve AT(1), AT(2) and AT(1-7) angiotensin receptors.

Controlled trial of the effects of milk basic protein (MBP) supplementation on bone metabolism in healthy adult women.

Milk has more beneficial effects on bone health compared to other food sources. Recent in vitro and in vivo studies showed that milk whey protein, especially its basic protein fraction, contains several components capable of both promoting bone formation and inhibiting bone resorption. However, the effects of milk basic protein (MBP) on bone metabolism of humans are not known. The object of this study was to examine the effects of MBP on bone metabolism of healthy adult women. Thirty-three normal healthy women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for six months. The bone mineral density (BMD) of the left calcaneus of each subject was measured at the beginning of the study and after six months of treatment, by dual-energy x-ray absorptiometry. Serum and urine indices of bone metabolism were measured at the base line, three-month intervals, and the end of the study. Daily intake of nutrients was monitored by a three-day food record made at three and six months. The mean (+/- SD) rate of left calcaneus BMD gain of women in the MBP group (3.42 +/- 2.05%) was significantly higher than that of women in the placebo group (2.01 +/- 1.75%, P = 0.042). As compared with the placebo group, urinary cross-linked N-teleopeptides of type-I collagen/creatinine and deoxypyridinoline/creatinine were significantly decreased in the MBP group (p < 0.05), while no significant differences between the two groups were observed in serum osteocalcin and bone-specific alkaline phosphatase concentrations. A daily MBP supplementation of 40 mg in healthy adult women can significantly increase their BMD independent of dietary intake of minerals and vitamins. This increase in BMD might be primarily mediated through inhibition of osteoclast-mediated bone resorption by the MBP supplementation.

RGD-independent binding of integrin alpha9beta1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction.

ADAMs (a disintegrin and metalloproteases) mediate several important processes (e.g. tumor necrosis factor-alpha release, fertilization, and myoblast fusion). The ADAM disintegrin domains generally lack RGD motifs, and their receptors are virtually unknown. Here we show that integrin alpha(9)beta(1) specifically interacts with the recombinant ADAMs-12 and -15 disintegrin domains in an RGD-independent manner. We also show that interaction between ADAM-12 or -15 and alpha(9)beta(1) supports cell-cell interaction. Interestingly, the cation requirement and integrin activation status required for alpha(9)beta(1)/ADAM-mediated cell adhesion and cell-cell interaction is similar to those required for known integrin-extracellular matrix interaction. These results are quite different from recent reports that ADAM-2/alpha(6)beta(1) interaction during sperm/egg fusion requires an integrin activation status distinct from that for extracellular matrix interaction. These results suggest that alpha(9)beta(1) may be a major receptor for ADAMs that lack RGD motifs, and that, considering a wide distribution of ADAMs and alpha(9)beta(1), this interaction may be of potential biological and pathological significance.

Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia.

The combined effect of granulocyte-colony stimulating factor (GCSF) and hyperthermia in the treatment of experimental tumours was studied to examine the possible involvement of activated granulocytes in the antitumour effect of hyperthermia. Two weeks after transplantation of SCC VII cells (1 x 10(5)) into the instep of the left leg of C3H/HeJ male mice, the mice were given subcutaneous injections of GCSF (0.2 mg/kg) for 4 days. On day 4, hyperthermia was applied locally at 43 degrees C for 40 min. Hyperthermia inhibited the tumour growth, and this effect was enhanced by pre-treating the animals with GCSF. The numbers of circulating neutrophils in control and GCSF-treated mice were 2728 +/- 517/microl and 3124 +/- 194/microl, respectively (p = 0.53). Hyperthermia increased the number of neutrophils to 4409 +/- 700/microl (p < 0.05). Hyperthermia combined with GCSF significantly increased the number of netrophils to 5479 +/- 691/microl (p < 0.01). Chemiluminescence analysis using L-012 revealed that GCSF enhanced the generation of reactive oxygen species by about 10-fold. Glutathione contents in tumours 24 h after hyperthermia decreased by about 50% in both the hyperthermia groups with or without GCSF, as compared to those in the control. The GCSF-enhanced anti-tumour activity of hyperthermia was markedly inhibited by administration of a long-acting superoxide dismutase derivative (SM-SOD). These results suggest that GCSF activates the ability to generate active oxygen species by neutrophils and, thereby, enhances the anti-tumour effect of hyperthermia.

Highly divergent sequences of the pollen self-incompatibility (S) gene in class-I S haplotypes of Brassica campestris (syn. rapa) L.

Self-incompatibility (SI) enables flowering plants to discriminate between self- and non-self-pollen. In Brassica, SI is controlled by the highly polymorphic S locus. The recently identified male determinant, termed SP11 or SCR, is thought to be the ligand of S receptor kinase, the female determinant. To examine functional and evolutionary properties of SP11, we cloned 14 alleles from class-I S haplotypes of Brassica campestris and carried out sequence analyses. The sequences of mature SP11 proteins are highly divergent, except for the presence of conserved cysteines. The phylogenetic trees suggest possible co-evolution of the genes encoding the male and female determinants.

Dietary magnesium supplementation affects bone metabolism and dynamic strength of bone in ovariectomized rats.

We evaluated the effect of magnesium supplementation on apparent calcium absorption, bone metabolism and dynamic bone strength in ovariectomized (OVX) rats as a model of postmenopausal women. Two groups of OVX rats were fed a 0.05% Mg diet or a 0.15% Mg diet, and one group of sham-operated rats was fed the 0.05% Mg diet for 42 d. We collected feces and urine of all rats for 3-d periods starting from d 3, 10, 17, 24, 31 and 38 of the feeding experiment for calcium and magnesium balance studies. Urine was collected for 24 h from d 41 of the feeding experiment for measuring deoxypyridinoline. After the 42 d, the rats were killed, serum prepared and femora excised. The apparent calcium absorption in the OVX rats fed 0.15% Mg was significantly lower than both other groups. Additionally, the urinary excretion of deoxypyridinoline (a bone resorption marker) and the serum parathyroid hormone level of the OVX rats fed the 0.15% Mg diet were significantly lower than in the OVX rats fed 0.05% Mg. Serum osteocalcin (a bone formation marker) in the OVX rats fed the 0.15% Mg diet was significantly higher than in the OVX rats fed 0.05% Mg. The breaking force and breaking energy of the femur in the OVX rats fed the 0.15% Mg diet were significantly higher than in the OVX rats fed the 0.05% Mg diet. These results indicate that magnesium supplementation reduces apparent calcium absorption, but promotes bone formation and prevents bone resorption in OVX rats. Moreover, our results indicate magnesium supplementation increases the dynamic strength of bone.

Abnormal cell morphology and cytotoxic effect are induced by 6-0-palmitol-ascorbate-2-0-phosphate, but not by ascorbic acid or hyperthermia alone.

A new derivative of ascorbic acid (AsA), 6-0-palmitoyl-ascorbate 2-0-phosphate (Asc2P6Pal) was developed to enhance the antitumor activity of AsA. When Ehrlich ascites tumor cells were treated with 50 microM Asc2P6Pal at 37 degrees C or 42 degrees C for 1 h and then cultured for 20 h, most of cells exhibited some morphological abnormalities, including exudation of intracellular granules together with other contents on the cell membrane surface, resulting in cell fragmentation. The abnormal features were further enhanced by a long term culture for 96 h and heat treatment at 42 degrees C. In contrast, no abnormality was detected for untreated cells or cells treated with AsA (free acid) at 37 degrees C or 42 degrees C. Cells cultured for 96 h after the treatment suffered from inhibition of DNA synthesis and proliferation. This inhibition was markedly enhanced by combination with the hyperthermic treatment at 42 degrees C, but not for a short-term culture of 20 h after the treatment. No effects were seen upon similar treatment with AsA. The abnormal cells produced during culture for 20 h after the treatment were evaluated to be viable, because they failed to be stained with trypan blue and retained most of the DNA synthesizing ability of Asc2P6Pal-untreated cells. However, they appeared and died after a continuous 76 h of culture (96 h).

Antithrombotic activity of avian crown dermatan sulfate.

The antithrombotic activity of dermatan sulfate from avian crown with the mean molecular weight of 38000 was compared to those from bovine intestine with the mean molecular weight of 16000 in vivo and in vitro. In an in vitro test, bovine intestine dermatan sulfate exhibited stronger effects on stimulation of heparin cofactor II and activation of Glu-plasminogen by tissue plasminogen activator. In vivo, avian crown dermatan sulfate more effectively prevented the development of thrombus in a rat deep vein thrombosis model. The measurement of plasma levels of these two kinds of dermatan sulfate revealed that avian crown dermatan sulfate circulated in higher concentration and longer duration than bovine intestine dermatan sulfate after intravenous administration to rats.

Rotundial, a new natural mosquito repellent from the leaves of Vitex rotundifolia.

A new natural mosquito repellent was isolated from fresh leaves of Vitex rotundifolia. Its structure was elucidated by an extensive NMR spectral analysis to be a cyclopentene dialdehyde named rotundial. This compound possessed potent repelling activity against Aedes aegypti.

[A case report of rectal cancer with lymph node metastasis effectively treated by neoadjuvant chemotherapy of 5-FU oral and low-dose CDDP transarterial administration].

A 52-year-old man was diagnosed as having rectal cancer. Miles' operation with regional lymph node dissection was performed in April 1989. CT scanning and MRI examination performed in May 1992 showed local recurrence in a lymph node of the pelvic cavity (282). We implanted a catheter in the left internal iliac artery and connected it to an implanted injection port through a subcutaneous tunnel. 5-FU was administered orally at 300 mg daily. CDDP was injected through an injection port at a dose of 20 mg/body/day twelve times and 10 mg/body/day six times. CT scanning showed a change in the size of the tumor, with a reduction rate of 75%. Thereafter, we performed a radical operation in September 1992. The histopathological effect was Grade 2.

Plasma amino acid profile in relation to arterial ketone body ratio in surgical patients.

A total of 357 plasma amino acid profiles from 93 surgical patients were statistically analyzed in relation to the changes in arterial ketone body ratio, which reflects the hepatic mitochondrial redox state. When the arterial ketone body ratio was above 0.7, all plasma amino acid levels were within the normal range. When it was between 0.7 and 0.4, plasma levels of aspartate, glutamate, valine, isoleucine, leucine, ornithine, and arginine decreased, and plasma levels of tyrosine, phenylalanine, proline, and methionine increased. Furthermore, when it was below 0.4, almost all plasma amino acids markedly increased. These results indicate that arterial ketone body ratio accurately reflects the alterations in plasma amino acid profile, and can serve as an indicator for providing nutritional support by amino acid supplement in surgical patients.

[A case of pseudotumor cerebri associated with colon cancer].

A case of pseudotumor cerebri associated with iron deficiency anemia due to colon cancer is reported in a 37-year-old woman. Her initial symptoms were vomiting and severe headache. On physical examination, no lymph nodes and abdominal mass were palpable but marked anemia was noted in her skin and conjunctiva . Neurological examination revealed papilledema in her both eyes and stiff neck. There was no abnormal findings on CT scan on admission. Spinal puncture revealed CSF pressure as high as 620 mmH2O with normal cells, protein, sugar and chloride levels. Hematological examination revealed iron deficiency anemia and thrombocytosis. Angiography at third day revealed no sinus occlusion, but retention of contrast media was seen on the cortical vein of parietal lobe and right transverse sinus. Brain scintigram at sixth day revealed mild accumulation in left parietal lobe, so small venous infarction was suggested. There were two circumscribed stenotic lesions of right ascending colon in the barium enema, and right hemicolectomy was achieved. The pathological diagnosis was adenocarcinoma. The symptoms of pseudotumor cerebri was completely disappeared soon after the surgery together with resolution of anemia. She lives with no deficits now 1 year 3 months after surgery. In conclusion much attention is necessary to a patient of pseudotumor cerebri with iron deficiency anemia for the presence of cancer, because not only this central nervous system lesion is reversible and curable but also the cancer itself may be curable by surgery.

Heliotherapy of pityriasis lichenoides chronica.

Fifteen patients with pityriasis lichenoides chronica (parapsoriasis guttata) were treated with sunlight irradiation during the summer months at seaside resorts under the supervision of the authors. Complete clearing occurred in 1 of the patients, almost complete clearing in 8, definte improvement in 4, temporary clearing in 2. All patients responded beneficially and no worsening was noted in these 15 cases. In an additional six cases who were instructed to expose themselves to sunlight similar results were obtained.