Investigating the potential role of vitamin E in modulating the immunosuppressive effects of tylvalosin and florfenicol in broiler chickens.

Tylvalosin (TVS) is a third-generation macrolide drug used for prophylaxis and treatment of mycoplasma, however; it is supposed to possess an immunosuppressive effect. In the current study, the immunosuppressive effect of TVS and florfenicol (FFC) and the potential immunomodulatory role of Vit E were investigated. The experiment included one day old chick groups treated with either TVS, FFC, Vit E, TVS/Vit E, FFC/Vit E and control non-treated group. Chicks were vaccinated with inactivated H9N2 avian influenza (AI) vaccine and humoral antibody titers to viral antigen as well as innate immunity (serum lysozyme activity and nitric oxide levels) were evaluated. Total and differential leucocytic counts, serum liver enzymes level, blood leucocytic DNA damage and cellular area percentages within the lymphoid organs were also screened. Treatment with TVS and FFC significantly decreased immune response of chickens while treatment with Vit E improved the humoral immune response at 4 and 5weeks post-vaccination. Vit E also significantly increased the cellular immune response. The combination of Vit E with either TVS or FFC modulated their immunosuppressive effect and resulted in mild immunostimulatory effects. TVS alone induced a genotoxic effect on chickens' blood leucocytes and the genotoxicity was inhibited by combination of TVS with Vit E. Histopathology revealed that chickens treated with either TVS or FFC exhibited toxic effect on the lymphatic tissues.

Immunogenicity and protective efficacy of the norovirus P particle-M2e chimeric vaccine in chickens.

The ectodomain of the influenza matrix protein 2 (M2e) is highly conserved across strains and has been shown to be a promising candidate for universal influenza vaccine in the mouse model. In this study, we tested immune response and protective efficacy of a chimeric norovirus P particle containing the avian M2e protein against challenges with three avian influenza (AI) viruses (H5N2, H6N2, H7N2) in chickens. Two-week-old specific pathogen free chickens were vaccinated 3 times with an M2e-P particle (M2e-PP) vaccine via the subcutaneous (SQ) route with oil adjuvant, and transmucosal routes (intranasal, IN; eye drop, ED; microspray, MS) without adjuvant. M2e-PP vaccination via the SQ route induced significant IgG antibody responses which were increased by each booster vaccination. In groups vaccinated via IN, ED or MS, neither IgG nor IgA responses were detected from sera or nasal washes of immunized birds. The M2e-PP vaccination via the SQ route significantly reduced the virus shedding in the trachea and the cloaca for all three challenge viruses. Despite the absence of detectable IgG and IgA responses in birds vaccinated with the M2e-PP via intranasal routes, a similar level of reduction in virus shedding was observed in the IN group compared to the SQ group. Our results supports that the universal vaccine approach using M2e-based vaccine can provide cross-protection against challenge viruses among different HA subtypes although the efficacy of the vaccine should be enhanced further to be practical. Better understanding of the protective immune mechanism will be critical for the development of an M2e-based vaccine in chickens.

Ultrasound-modulated light tomography assessment of osteoporosis.

We present a preliminary series of clinical experiments showing that ultrasound modulation of light in tissues allows tissue properties to be determined well inside the tissue. In this series of clinical experiments the optical scattering coefficient determined by the optical technique is compared with the bone density obtained by dual x-ray absorption. A correlation of 0.84 (p = 0.005) was found for a limited number of patients, showing the potential of this technique for the assessment of osteoporosis.

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.

Regulation of TNF-alpha by 1alpha,25-dihydroxyvitamin D3 in human macrophages from CAPD patients.

BACKGROUND: We have previously reported that 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] accumulates in the dialysis fluid of uremic patients treated by continuous ambulatory peritoneal dialysis (CAPD). It has been reported that this metabolite regulates the production of cytokines by monocytes/macrophages. Since tumor necrosis factor-alpha (TNF-alpha) initiates an inflammatory cascade during peritonitis, the aim of the present study was to investigate the effect of 1alpha, 25(OH)2D3 on the production of TNF-alpha by human peritoneal macrophages (HPMs). METHODS: HPMs were obtained from patients on CAPD. Cells were incubated with various concentrations of 1alpha, 25(OH)2D3, 1alpha,24(S) dihydroxyvitamin D2 [1alpha,24(S)(OH)2D2] or 25-hydroxyvitamin D3 (25-OH-D3) for 16 hours. This was followed by lipopolysaccharide (LPS; 1 microg/mL) incubation for 2.5 to 6 hours. TNF-alpha protein production was determined by enzyme-linked immunosorbent assay. TNF-alpha mRNA was assayed by the reverse transcriptase-polymerase chain reaction procedure, using internal synthetic mRNA standards for quantitative results. RESULTS: Incubation of HPMs with 1alpha,25(OH)2D3 prior to stimulation with LPS dose dependently inhibited the expression of TNF-alpha on both mRNA and protein levels. Similar results were obtained with the less calcemic vitamin D2 analogue 1alpha,24(S)(OH)2D2. Incubation of HPMs with 25-OH-D3 also revealed a down-regulation of TNF-alpha expression. Since this down-regulatory effect was blocked by ketoconazole, it is likely that this effect was caused by the conversion of 25-OH-D3 into 1alpha,25(OH)2D3 by HPMs. CONCLUSIONS: 1alpha,25(OH)2D3 has a potent inhibitory effect on the production of TNF-alpha by LPS-activated HPMs. We hypothesize that 1alpha, 25(OH)2D3 may constitute a regulatory mechanism that, by controlling the intensity of the inflammatory response of the peritoneum, will moderate tissue damage during peritonitis.

Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats.

The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food.

Dietary treatment of hypercholesterolemia: do dietitians do it better? A randomized, controlled trial.

PURPOSE: Current guidelines of the National Cholesterol Education Program (NCEP) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic. We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians. SUBJECTS AND METHODS: Hypercholesterolemic patients detected during a cholesterol screening project were randomly assigned to receive dietary counseling by a physician only (70 patients) or by a physician and a registered dietitian (66 patients). Patients were observed for 1 year to determine compliance with NCEP guidelines. RESULTS: At 3 months, the mean (+/- SD) decrease in the serum low-density lipoprotein (LDL) cholesterol level was 7% +/- 11% in the physician group and 12% +/- 10% in the dietitian group (P <0.004). A decrease of 10% or more in the LDL cholesterol level was seen in 25 patients (36%) in the physician group and 43 patients (65%) in the dietitian group (P <0.001). Only 40 (29%) of the patients in both groups achieved their NCEP target goals at 3 months. The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months, both groups lost about half of the beneficial effects on LDL cholesterol levels, and the difference between the two groups diminished. CONCLUSIONS: The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians. However, long-term compliance remains inadequate. For patients at high risk, consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications.

Cord leptin level and fetal macrosomia.

OBJECTIVE: To determine the relationships among serum leptin, insulin-like growth factor-I, and insulin levels in large for gestational age (LGA) infants. METHODS: Serum samples were collected from maternal veins and umbilical arteries of 52 consecutive, term, LGA neonates of nondiabetic mothers. Maternal and neonatal serum samples were analyzed for levels of leptin, insulin-like growth factor-I, and insulin by specific radioimmunoassays. Multiple regression analysis was used to determine independent risk factors for fetal macrosomia. RESULTS: The independent risk factor significantly associated with fetal macrosomia was umbilical cord leptin concentration (P <.01, beta = 0.59). There was a statistically significant correlation between umbilical cord leptin and insulin-like growth factor-I levels and birth weight (r = 0.51, P <.01; r = 0.37, P <.01; respectively). The correlation between umbilical cord insulin levels and birth weight was not statistically significant (r = 0.06, P =.63), nor was that between maternal body mass index and birth weight (r = 0.09, P =.50). CONCLUSION: Our data showed that umbilical cord leptin concentration was an independent risk factor for fetal macrosomia.

Estrogen controls expression and bioresponse of 1,25-dihydroxyvitamin D receptors in the rat colon.

Estrogen receptors are extensively expressed in the gastrointestinal tract, however their physiological role is not clear yet. Estrogen and 1,25-dihydroxyvitamin D [1,25(OH)2D3] apparently share common activities in the intestine such as growth-suppressing effects on the colonic mucosa and positively influence intestinal calcium absorption. In view of our previous studies showing up-regulation of vitamin D receptors (VDR) in the duodenal mucosa and in osteoblasts, the present study was designed to address a possible interaction between estrogen and the vitamin D endocrine system in the colonic mucosa. Three groups of female rats were studied: sham operated ('Sham'), ovariectomized ('OVX'), and ovariectomized estrogen-treated ('OVX+E'). VDR gene expression was assessed by Northern blot analysis, VDR protein expression was assessed by ligand-binding assays, and Western-blotting. Endogenous 1,25(OH)2D3 bioactivity in colonic mucosal extracts was assessed by alkaline phosphatase activity and calbindin-9kD mRNA expression. Northern blots revealed marked increase in band intensity corresponding with the VDR mRNA product in 'Sham' or 'OVX+E' vs. 'OVX'. In ligand-binding experiments, 1,25(OH)2D3 was shown to bind specifically to a single class of receptors in extracts obtained from each of the groups (Kd--0.03 nM). The maximal VDR binding capacity of colonic mucosal extracts was 203 +/- 23 fmol/mg protein in 'Sham', 362 +/- 41 in 'OVX+E' and 102 +/- 15 in 'OVX' ('Sham' or 'OVX+E' vs. 'OVX', p < 0.001). Western-blot analysis also revealed higher VDR protein expression in the estrogen-exposed animals. Alkaline phosphatase activity and calbindin-9kD mRNA expression were significantly higher in colonic mucosal extracts from estrogen-exposed rats. Estrogen increases VDR gene transcript level, protein expression and endogenous 1,25(OH)2D3 bioactivity in colonic mucosa, which may suggest that some of the estrogen activities in the colonic mucosa, such as its growth-suppressing effect, could be mediated, at least in part, by an increase in colonic mucosa responsiveness to endogenous 1,25(OH)2D3.

A protective role of dietary vitamin D3 in rat colon carcinogenesis.

The aim of the present work was to gain insight into a putative anticancer effect of dietary vitamin D3 (cholecalciferol) in a rat model of colon carcinogenesis. Male rats were assigned to three different dietary groups. The dietary regimens were based on a standard murine-defined diet (AIN-76A) or a stress diet containing 20% fat, reduced Ca2+ concentration, a high phosphorus-to-Ca2+ ratio, and either low or high vitamin D3 content. Colorectal cancer was induced by administration of the procarcinogen 1,2-dimethylhydrazine (DMH). Blood Ca2+, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and 25-hydroxyvitamin D3 [25(OH)D3] levels were measured in DMH-treated rats and in respective weight- and age-matched dietary control groups. Colonic epithelial proliferation was assessed by determining thymidine kinase (TK) activity, bromodeoxyuridine (BrdUrd) incorporation into crypt cell DNA, and the mean labeling index along the colonic crypt continuum. Maintenance of rats on the stress diet either unmodified or supplemented with vitamin D3 in the absence of carcinogen treatment provoked a time-dependent rise in colonic TK activity and hyperproliferation of colonic epithelium. DMH treatment of rats maintained on the standard diet caused a marked increase in the proliferative indexes of colonic epithelium and in expansion of the crypt proliferative compartment. TK activity and the crypt mitotic zone were significantly augmented in the animal group fed the stress diet. Supplementary vitamin D3 abrogated the stress diet-enhanced colonic responses to the carcinogenic insult. Colon tumor multiplicity was fourfold higher in animals fed the stress diet than in animals maintained on a standard diet. The marked rise in colonic tumor multiplicity and adenocarcinoma incidence in rats fed the stress diet was obliterated by supplemental dietary vitamin D3. Cumulatively, the present results indicate that dietary vitamin D3 impedes the neoplastic process in murine large intestine and strengthen the view that inappropriate changes in dietary components and micronutrients are contributory determinants of colorectal cancer.

In colorectal carcinoma patients, serum vitamin D levels vary according to stage of the carcinoma.

BACKGROUND: Epidemiologic studies have demonstrated an inverse correlation between dietary calcium and vitamin D intake and the incidence of colorectal carcinoma. Elevated serum levels of 25-hydroxyvitamin D3 (25-OH-D3) are associated with a major reduction in the incidence of this neoplasm. The reduction in tumor size and number induced by calcium supplements in an experimental carcinogenesis model was neutralized by vitamin D3 deficiency. To the authors' knowledge, vitamin D serum levels have never been determined previously in colorectal carcinoma patients. They compared serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 25-OH-D3, and parathyroid hormone (PTH) levels of colorectal carcinoma patients with those of healthy controls. METHODS: Serum 1,25(OH)2D3, 25-OH-D3, and PTH levels were determined in 84 colorectal carcinoma patients (10 with Stage I, 29 with Stage II, 25 with Stage III, and 20 with Stage IV) and 30 healthy controls, all of whom were normocalcemic and not taking calcium or vitamin D supplements. RESULTS: 25-OH-D3 serum levels were higher in cancer patients than controls, irrespective of stage. Serum 1,25(OH)2D3 decreased with advancing stage: 73 +/- 18, 48 +/- 16, 39 +/- 12, 34 +/- 13, and 75 +/- 20 pg/mL in Stages I, II, III, IV, and controls, respectively. There was a corresponding increase in serum PTH levels: 58.0 +/- 9.4, 73.7 +/- 14.4, 79.0 +/- 21.3, 100.4 +/- 30.9, and 51.2 +/- 3.9 pg/mL in Stages I, II, III, IV, and controls, respectively. Serum vitamin D metabolite levels did not correlate with gender, age, tumor localization, or histologic grade. CONCLUSIONS: An inverse correlation between serum levels of the active metabolite of vitamin D and colorectal carcinoma stage has been demonstrated for the first time, to the authors' knowledge, in colorectal carcinoma patients. Because 1,25(OH)2D3 has been shown to inhibit proliferation of colonic epithelial cells, decreased serum levels may facilitate the growth of colorectal carcinoma and influence its biologic behavior.

Estrogen increases 1,25-dihydroxyvitamin D receptors expression and bioresponse in the rat duodenal mucosa.

Menopause and estrogen deficiency are associated with apparent intestinal resistance to vitamin D, which can be reversed by estrogen replacement. The in vivo influence of estrogens on duodenal vitamin D receptor (VDR) was studied in three groups of rats: ovariectomized (OVX), sham-operated, and ovariectomized rats treated daily with estrogen (40 microg/kg BW) for 2 weeks (OVX + E). Estrogen administration to OVX rats resulted in a 2-fold increase in VDR messenger RNA transcripts. 1,25(OH)2D3 was shown to bind specifically to one class of receptors in duodenal mucosal extracts, with a dissociation constant of 0.03 nM. Binding was significantly increased in duodenal extracts from OVX + E rats, compared with OVX rats (735 +/- 81 vs. 295 +/- 26 fmol/mg protein; P < 0.001); a comparable, 1.5- to 2-fold increase in VDR protein expression was observed in Western blot analyzes of the duodenal mucosa. Markers of VDR activity were increased in estrogen-exposed rats: calbindin-9k messenger RNA transcript content was 1.4- to 1.6-fold higher, and alkaline phosphatase activity was 1.4- to 3-fold higher in sham-operated and OVX + E, respectively, compared with OVX. 25(OH)D, 1,25(OH)2D, or PTH levels were not altered by estrogen treatment. Cumulatively, these findings suggest that estrogen up-regulates VDR expression in the duodenal mucosa and concurrently increases the responsiveness to endogenous 1,25(OH)2D. Modulation of intestinal VDR activity by estrogen, and subsequent influence on intestinal calcium absorption, could be one of the major protective mechanisms of estrogen against osteoporosis.

The protective effect of estrogen against chemically induced murine colon carcinogenesis is associated with decreased CpG island methylation and increased mRNA and protein expression of the colonic vitamin D receptor.

Epidemiological studies suggest that estrogen prevents neoplastic transformation in the intestinal mucosa. Estrogen was shown to increase the expression of vitamin D receptors (VDR) in a variety of tissues. 1,25-Dihydroxyvitamin D [1,25-(OH)2D] and several of its analogues are known as potent antineoplastic and prodifferentiative in many cell types, including colon-derived cells. The present study was designed to examine the effect of estradiol (E2) on dimethylhydrazine (DMH)-induced colon cancer in rats, and the possibility that E2 may exert its protective effect on the colon through modulation of the vitamin D-endocrine system. The in vivo effect of E2 on DMH-induced colorectal cancer was studied in four groups of ovariectomized female rats: (I) untreated control, (II) E2 treated, (III) DMH treated, and (IV) combined E2 and DMH treated. Significantly higher uterine weights and higher colonic estrogen receptor content confirmed the effectiveness of ovariectomy and E2 replacement. The number of malignant tumors in group IV was 2.3+/-1.1 (mean +/- SE) per rat, compared with 8.1+/-1.9 in group III (P < 0.001). Exposure to estrogen was associated with a marked increase in VDR mRNA content and VDR protein expression in the normal colonic mucosa. In tumor extracts VDR protein expression was considerably lower compared with normal mucosa. Estrogen treatment did not affect serum levels of 25(OH)D, 1,25(OH)2D, and PTH. Significant CpG island methylation in the VDR gene was observed in colonic tissue DNA harvested from rats treated with DMH, but not in colonic mucosae from rats treated with DMH + E2. The highest frequency of CpG methylation in the VDR gene was detected in DNA extracted from cancer tissue rims. In summary, the protective effect of estrogen against chemically induced colonic carcinogenesis is associated with reduced methylation of the VDR gene and with upregulation of both VDR gene transcription and protein expression. We suggest that estrogen may interfere with the process of CpG DNA methylation in the colonic mucosa to prevent silencing of the VDR gene. Increased VDR activity could be one of the mechanisms by which estrogen protects against neoplastic transformation in the colon.

Hepatitis B and C markers among alcoholics in Israel: high incidence of HCV infection.

Patients with alcoholic liver disease have an increased prevalence of viral hepatitis. However, the role of demographic characteristics has not been adequately delineated. Therefore, we examined and compared the seroprevalences of hepatitis B and C in Israeli alcoholic patients to that of blood donors control group by their country of birth and origin. Hepatitis B surface antigen, hepatitis B core antibody and hepatitis C virus antibody testing (second generation ELISA) and a confirmatory recombinant immunoblot assay was performed on 496 alcoholic attending an alcoholic abstinence program and compared to 193,806 randomly non-alcoholic blood donors on the basis of their country of birth. Three hundred twenty-eight alcoholic patients (66%) were immigrants and Israeli born Jews and 168 (34%) were Israeli Arabs. Of the 496 alcoholic patients, 24 (4.8%) were HBsAg positive, 38 (7.6%) were anti HCV positive, and 2 (North African Jews) were positive for both markers. HBsAg was detected in 13 (3.9%) immigrant and Israeli Jews and 11 (6.5%) Israeli Arabs, significantly higher than in the adjusted non alcoholic blood donors (p < 0.01). Anti-HCV was detected in 33 (10%) immigrants and Israeli Jews and 5 (2.9%) Israeli Arabs, significantly higher than in the control group (p < 0.005). In the subgroup alcoholic Jews there was no significant difference in hepatitis B seropositivity among alcoholic that were native Israeli, Eastern Europe and former USSR, and Western Europe and American immigrants comparing to the control group. In contrast, anti-HCV recombinant immunoblot assay seropositivity in alcoholic Jews from all subgroups was significantly greater than in non alcoholic blood donors (p < 0.001). Odds analysis of all ethnic groups revealed that alcoholism requiring detoxification have a significant risk factor for hepatitis C more than hepatitis B (p < 0.001). The increased seroprevalence of hepatitis C among Israeli alcoholic patients, regardless their country of birth and origin, suggest that alcoholism is likely to have a predisposing factor for HCV infection.

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.

Gorging and plasma HDL-cholesterol--the Ramadan model.

OBJECTIVES: To evaluate the effect of a single evening meal (gorging) on plasma lipids and lipoproteins in normal individuals observing the Ramadan Fast. During the Ramadan month, Muslims refrain from food and liquids during the day and eat a large meal after sundown. DESIGN: Sequential measurement of plasma lipids and lipoproteins in Muslims observing the Ramadan Fast and non-fasting individuals. SETTING: The study was conducted in the Bedouin town of Rahat, in the northern Negev area of Israel. SUBJECTS: Twenty-two healthy subjects who fasted during Ramadan and 16 non-fasting laboratory workers, were studied before Ramadan, at week 1, 2 and 4 of the Ramadan month, and again four weeks after the end of Ramadan. RESULTS: Plasma high-density lipoprotein cholesterol (HDL) rose significantly (P < 0.001) at the week 4 measurement, returning to basal levels 4 weeks after the end of Ramadan. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), very-low density lipoprotein cholesterol (VLDL), and lipoprotein (a) [Lp(a)] did not change significantly. CONCLUSIONS: Plasma HDL increased by 23% after four weeks of gorging. The dietary change did not affect the composition of other lipoproteins, such as LDL, VLDL or Lp(a), other plasma biochemical parameters, or BMI. Prolonged gorging, well tolerated by all individuals, is a very effective non-pharmacological method to increase plasma HDL-cholesterol.

Increase of serum lipoprotein (a) levels during growth hormone therapy in normal short children.

UNLABELLED: We studied the effect of growth hormone (GH) therapy on serum lipoprotein levels and the atherogenic index in short children without GH deficiency. Fasting blood samples were collected from ten (eight males) normal, short, prepubertal children, aged 6-12 years, before, during a 1-year course of GH therapy (0.1 IU/Kg/day), and 3 months after the cessation of GH administration. An increase in serum lipoprotein(a) [Lp(a)] levels of (mean% +/- SEM) 43 +/- 14, 58 +/- 18, 61 +/- 17 above the baseline levels was noted at 3 months (P < 0.05), 6 months (P < 0.01), and 1-year (P < 0.01) respectively after the beginning of GH administration. (ANOVA, P < 0.01). An inverse relationship between baseline serum Lp(a) concentrations and the percentage increment in Lp(a) after 9 months of GH therapy (r = -0.65, P < 0.05) was observed. GH therapy over a period of 1 year had no effect on plasma cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein cholesterol [HDL-C] concentrations and the atherogenic index. Three months after the cessation of GH therapy, serum Lp(a) levels were not significantly different from the pre-treatment values. CONCLUSIONS: Serum Lp(a) concentrations remained above pretreatment values during a 1-year period of GH treatment in short children without GH deficiency and declined shortly after cessation of therapy. Since GH therapy for short children without GH deficiency usually continues for several years, we suggest that serum Lp(a) levels should be determined and followed regularly in such children under prolonged GH therapy.

Whey deionization method of infant formula affects plasma lipids.

BACKGROUND: Casein has proved to be hypercholesterolemic. According to results of previous studies, the casein-to-whey ratio in infant formula influences plasma lipid profile. This study explored whether different methods of whey deionization also affect levels of plasma lipids. METHODS: Two types of a whey-predominant (whey 60%:casein 40%) formula which differed only in the methods used for whey deionization (ultrafiltration or electrodialysis), were fed to healthy newborn infants for 60 days, using a prospective, double-blind, randomized design. Formulas were otherwise identical in composition. RESULTS: Groups were similar in gestational age, gender, birth weight, and growth parameters. Evaluation of fasting plasma levels after 60 days revealed significantly higher values of total cholesterol (p < 0.001) and low-density lipoprotein cholesterol (p < 0.001) in infants fed ultrafiltrated whey compared with the same values in infants fed electrodialyzed whey. Plasma levels in the two groups of very low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides revealed no statistically significant differences. CONCLUSIONS: Plasma lipid profile in infancy is influenced by dietary protein, not only by the casein-to-whey ratio, but also by the method of whey deionization.

Prevalence of specific IgA and IgM anti-HBc antibodies compared with HBV DNA in the sera of HBsAg chronic carriers.

OBJECTIVE: We evaluated the significance of IgA antibodies directed against the hepatitis B virus core antigen (IgA anti-HBc) as a marker for viral replication. STUDY DESIGN/METHODS: Serum samples of 143 hepatitis B surface antigen (HBsAg) carriers and 189 HBsAg-negative subjects were studied. Hepatitis B virus (HBV) DNA was detected by polymerase chain reaction. IgA anti-HBc was determined by a capture enzyme-linked immunosorbent assay developed in our laboratory. The results were compared with those for IgM anti-HBc, which were determined by a commercially available method. RESULTS: IgA anti-HBc was detected in 57 (40%) and HBV DNA in 38 (27%) of the HBsAg carriers. Among the HBsAg-negative subjects, IgA anti-HBc and HBV DNA were detected simultaneously in four samples. All 42 HBV DNA-positive samples were IgA anti-HBc positive. IgM anti-HBc was detected in 27 (64%) of them. CONCLUSIONS: IgA anti-HBc is a sensitive marker for HBV replication, and its absence may exclude HBV replication. The role of IgA anti-HBc in monitoring response to therapy and predicting clinical course is being evaluated.