Medicagenic acid, the factor responsible for hemolytic activity of lucerne saponins.
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Animals↗
Biomedical subjects
S Shany
Publications and source records attributed to S Shany.
Lucerne saponins. II. Purification and fractionation of saponins from lucerne tops and roots and characterisation of the isolated fractions.
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Animal Feed↗
Lucerne saponins. 3. Effect of lucerne saponins on larval growth and their detoxification by various sterols.
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Animal Feed↗
Selection of high-affinity and high-specificity monoclonal antibodies for 1 alpha,25-dihydroxyvitamin D.
The preparation of high-affinity and high-specificity monoclonal antibodies to 1 alpha,25-dihydroxyvitamin D is described. Monoclonal antibodies were derived from Balb-c mice immunised with either 1 alpha-hydroxy-25,26,27-trinor-24-cholecalcioic acid or with 1 alpha-hydroxy-26,27-dinor-cholecalciferol-25-oxime, and spleen cells were hybridised with mouse myeloma cells. From six fusions nine monoclonal antibodies (MAb's) were selected from 676 antibody-secreting hybrids. Antibodies varied widely in their ability to bind 1 alpha,25-dihydroxyvitamin D3 (50% displacement of radioligand ranged from 25 - 900 pg); two had particularly useful characteristics for 1 alpha,25-dihydroxyvitamin D assay. MAb 5F2 has high affinity (Ka = 1.39 X 10(10) M-1) and does not discriminate between 1 alpha,25-dihydroxyvitamin D2 and D3, thus enabling the two forms to be measured together. MAb 1G7 is highly specific, having no cross-reactivity with 25-hydroxy-, 24,25-dihydroxy- or 25,26-dihydroxyvitamin D at concentrations found in normal human serum; this MAb has the potential to eliminate the lengthy extraction procedures involved in currently available assays for 1 alpha,25-dihydroxyvitamin D.
Animals↗
The effects of 1alpha,24(S)-dihydroxyvitamin D(2) analog on cancer cell proliferation and cytokine expression.
It is well established that 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), the active metabolite of vitamin D, plays a role in regulating proliferation and differentiation of cells, in addition to its classic function in mineral homeostasis. Recent studies have also provided evidence for the involvement of 1alpha,25(OH)(2)D(3) in regulating the immune system. However, therapeutic application of 1alpha,25(OH)(2)D(3) to hyperproliferative diseases such as cancer, or for immunologic purposes, is thwarted by its hypercalcemic activity. In order to overcome this obstacle, analogs of 1alpha,25(OH)(2)D(3) have been produced that exhibit decreased hypercalcemic activity while retaining the growth and immunologic regulating properties. In the present study, the efficacy of 1alpha,24(S)-dihydroxyvitamin D(2) (1alpha,24(S)(OH)(2)D(2)), a vitamin D(2) analog, in restraining cell proliferation was compared to that of 1alpha,25(OH)(2)D(3). In parallel studies, cancer cell lines were grown in increased concentrations (10(-10)-10(-7) M) of each compound for various incubation periods (1-4 days). Growth was assessed by measuring [(3)H]thymidine incorporation. The results revealed that 1alpha,24(S)(OH)(2)D(2) significantly inhibits proliferation to an extent similar to that observed for 1alpha,25(OH)(2)D(3). Moreover, incubating the human leukemia cell line, HL-60, with 1alpha,24(S)(OH)(2)D(2) resulted in an induction of differentiation of these promyelomonocyte cells into monocyte-macrophage-like cells, in a manner similar to that observed with 1alpha,25(OH)(2)D(3). Using a Western procedure, it was also shown that 1alpha,24(S)(OH)(2)D(2) like 1alpha,25(OH)(2)D(3) enhances the expression of vitamin D receptors (VDR) in the rat osteosarcoma cell line, ROS 17/2.8. The expression of tumor necrosis factor (TNF) alpha (TNF-alpha) in human peritoneal macrophages (HPM) obtained from uremic patients treated with continuous ambulatory peritoneal dialysis (CAPD) was found to be regulated by 1alpha,25(OH)(2)D(3) as well as by 1alpha,24(S)(OH)(2)D(2). Incubations of HPM with 1alpha,25(OH)(2)D(3) or 1alpha,24(S)(OH)(2)D(2), have inhibited the expression of TNF-alpha on both mRNA and protein levels. These results suggest that 1alpha,25(OH)(2)D(3) has a role in controlling the rate of inflammation in the peritoneal cavity of CAPD treated patients. Since 1alpha,24(S)(OH)(2)D(2) does not cause hypercalcemia, the present results encourage the possible use of this vitamin D(2) analog in the treatment of cancer and hyper-inflammatory diseases.
Animals↗
Losses of 25-hydroxyvitamin D in peritoneal fluid: possible mechanism for bone disease in uremic patients treated with chronic ambulatory peritoneal dialysis.
Despite a good control of serum phosphate levels, bone disease still occurs in patients treated with chronic ambulatory peritoneal dialysis (CAPD). The purpose of this study was to determine if 25-hydroxyvitamin D (25-OH-D) penetrates through the peritoneal membrane and whether chronic peritoneal dialysis may thereby decrease the serum 25-OH-D levels. In 10 CAPD-treated patients the serum 25-OH-D was 8.8 +/- 1.1 ng/ml, which is significantly lower than in the hemodialysis-treated group (15.5 +/- 2.3 ng/ml) and lower than in healthy controls (30.3 +/- 3.6 ng/ml). The mean total daily loss of 25-OH-D in the peritoneal fluid was 1,491 +/- 260 ng/day. The serum 25-OH-D binding capacity was significantly lower in the CAPD group than in normal controls. The mean daily loss of 25-OH-D binding capacity in the dialysate was 153 +/- 28 nmol/day. We conclude that permeability of the peritoneal membrane to middle-size proteins leads to loss of 25-OH-D binding protein, and this increases loss of 25-OH-D. Low levels of 25-OH-D in plasma may aggravate the symptoms of osteodystrophy of renal failure in patients treated with CAPD.
25-Hydroxyvitamin D 2↗
Mineral and endocrine metabolism during fracture healing in dogs.
The blood levels of parathormone (PTH), calcitonin (CT), vitamin D metabolites, calcium, phosphate, magnesium and alkaline phosphatase (AKP) were determined in 13 young dogs with experimental fractures of long bones. The parameters were measured before the fracture and during healing until the appearance of an early callus. Serum Ca levels were significantly reduced immediately after the fracture (10.95 +/- 0.30 mg/dl to 10.25 +/- 0.25 mg/dl; p less than 0.05). Significant rises in serum levels of PTH (0.99 +/- 0.10 ng/ml to 1.57 +/- 0.22 ng/ml; p less than 0.01); CT (0.14 +/- 0.01 ng/ml to 0.18 +/- 0.01 ng/ml; p less than 0.05); 24,25-dihydroxyvitamin D (13 +/- 2 ng/ml to 19 +/- 3 ng/ml; p less than 0.01) and AKP (153 +/- 24 U/l to 211 +/- 26 U/l; p less than 0.01) were noted during fracture repair. A reduction in serum levels of 25-hydroxyvitamin D (22 +/- 2 ng/ml to 15 +/- 1 ng/ml; p less than 0.001) was noted at the same time. The parameters returned or tended to return to normal levels during callus development. The data demonstrate the changes in levels of Ca-regulating hormones in response to bone injury. This suggests that CT and 24,25-dihydroxyvitamin D (24,25-(OH)2-D) can be associated with the process of callus formation.
Alkaline Phosphatase↗
The influence of age and sex on blood levels of calcium-regulating hormones in dogs.
In order to study age- and sex-related changes in calcium-regulating hormones, serum levels of parathormone (PTH), calcitonin (CT), and vitamin D metabolites were determined in 20 young dogs and 11 old dogs. A highly significant increase in serum levels of PTH was observed in old dogs (1.65 +/- 0.09 ng/ml versus 1.05 +/- 0.09 ng/ml in young animals) (p less than 0.001). Serum levels of 25-(OH)-D were significantly decreased in old dogs (11.24 +/- 2.03 ng/ml compared to 20.59 +/- 1.57 ng/ml in young dogs) (p less than 0.001). No significant differences in serum levels of 1,25-(OH)2-D, 24,25-(OH)2-D, and CT were found between young and old dogs. Serum CT levels were higher in males, especially in old animals. Young females had significantly higher serum levels of 25-(OH)-D than males. It seems that for some reason old dogs are in a relative state of vitamin D deficiency and hyperparathyroidism, which suggests the cause of skeletal alterations related to aging. A similar situation is observed in human geriatric patients.
Aging↗
A combined community strategy to reduce cholesterol and other risk factors.
Our primary objective was to conduct an integrated program to reduce coronary risk factors in the population of an Israeli kibbutz. The population-based objective was to reduce the mean community total cholesterol level. The individual-based objective was to provide counseling and treatment for individuals at high risk and to reduce individual total and low-density lipoprotein cholesterol levels. The intervention included food policy changes in the central kibbutz kitchen, health education programs aimed at all age groups, and health counseling for individuals at risk. Evaluation was by questionnaire at baseline and at the end of two years, blood lipoproteins, and monitoring of all food purchased by the kibbutz. Fifty-three percent of the adult population (100 of 187) had borderline to high baseline total cholesterol levels. At one year, 27% of these were in the normal category. Egg consumption dropped by 6%, liquid oil by 7%, and red meat by close to 19%. Consumption of fish, chicken meat, and vegetarian patties increased. Consumption of 1% milk increased by almost 300%. We conclude that an integrated health education program targeting individuals and the community together can be effective in reducing risk factors for coronary artery disease.
Adult↗
The novel analog 1,24(S)-dihydroxyvitamin D2 is as equipotent as 1,25-dihydroxyvitamin D3 in growth regulation of cancer cell lines.
The physiologically active metabolite of the vitamin D seco-steroid hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a major regulator of mineral homeostasis. Recent evidence also suggests its role in regulating proliferation and differentiation of cells, including cancer cells. Therapeutic application of 1,25(OH)2D3 to hyperproliferative disease, such as cancer, is thwarted by its hypercalcemic activity. To overcome this problem, analogs of 1,25(OH)2D3 have been produced which retain growth regulating properties and exhibit decreased hypercalcemic activity. In the present study, the efficacy of the vitamin D2 analog, 1,24(S)-dihydroxyvitamin D2 (1,24(S)-(OH)2D2) in the inhibition of cancer cell proliferation and in inducing differentiation of cancer cells was compared to that of 1,25(OH)2D3. By the [3H]-thymidine incorporation procedure, 1,24(S)-(OH)2D2 is as equipotent as 1,25(OH)2D3 in inhibiting the proliferation of five different cell lines, ROS 17/2.8, the rat osteosarcoma cell line, MCF-7, the human breast cancer cell line, HD-11, the chick bone marrow v myc transformed cell line, HT-29, the human colon cancer cell line and HL-60, the human leukemia cell line. The inhibitory action was dose and time-dependent. The NBT reduction method indicated that 1,24(S)-(OH)2D2 induces the differentiation of the human leukemia cell (HL-60) to the same extent as 1,25(OH)2D3. Notwithstanding the vast similarity between 1,24(S)-(OH)2D2 and 1,25(OH)2D3 with regard to the above activities, they differ in their effects on calcium regulation. In conclusion, the present results encourage the use of 1,24(S)-(OH)2D2 for the treatment of cancer disease in vivo.
Animals↗