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PubMed1990

Oral induction of immunological tolerance to chromium in the guinea pig.

Metal alloys used in dentistry may elicit adverse side-effects. Contact allergic reactions to metals released from such alloys are among the most frequently encountered problems. In an earlier study, we observed that oral contacts with nickel or chromium salts did not sensitize, but rather decreased the risk of subsequent sensitization to these metals. In the present study, we focused on chromium allergy and extended our earlier observations by further dose-response studies. In addition, we compared different chromium valencies as to their potential oral tolerogenic effects. Development of immunological tolerance in chromium-fed guinea pigs was demonstrated by their inability to develop chromium hypersensitivity after a subsequent immunization attempt. For these studies, the techniques of immunization and skin testing were first improved. One feeding with a high dose of K2Cr2O7 (containing hexavalent chromium) was effective in full tolerance induction. In contrast, trivalent chromium (CrCl3) induced a distinctly lower degree of tolerance, whereas metallic chromium powder was not detectably tolerogenic after a limited number of feedings. Dose-frequency-response studies with K2Cr2O7 showed that full tolerance could also be induced by an increase in the number of feedings with sub-optimal tolerogenic doses. The present results therefore support our hypothesis that long-lasting oral contact with chromium-releasing metal alloys may ultimately result in strong immune tolerance to this metal in subjects without previous skin contact with it. This view is further supported by recent insights into the unique tolerogenicity of oral, as compared with gastro-intestinal, allergenic contacts.

Administration, Oral↗
PubMed2005

The role of biomembranes in chromium (III)-induced toxicity in vitro.

The role of biomembranes in the chronic toxicity of environmentally occurring chromium acetate hydroxide was investigated by using primary human fibroblasts. Transport of chromium acetate hydroxide across the plasma membrane of the cell, and the effects of chromium (III) ions on the plasma membrane as well as other intracellular membranes, were determined during six weeks of continuous exposure by using atomic absorption spectrometry, observation of cell morphology, membrane integrity assays (for lactate dehydrogenase leakage and lysosomal membrane disruption), and mitochondrial assays (for mitochondrial dehydrogenase activity and mitochondrial transmembrane potential analysis). The type of cell death induced by long-term exposure was determined in terms of phosphatidylserine externalisation, caspase-3 activation, and chromatin fragmentation. Chromium acetate hydroxide, at a concentration of 100 micromol/l, accumulated in exposed cells, inflicting plasma membrane damage and suppressing mitochondrial function. Antioxidant co-enzyme Q, at a concentration of 10 micromol/l, partially prevented plasma membrane damage and mitochondrial dysfunction. Exposure to chromium acetate hydroxide produced apoptosis, necrosis and an intermediate type of cell death in primary human fibroblasts. These results show that the plasma membrane and mitochondrial membrane are important targets for chronic chromium acetate hydroxide toxicity, and that this in vitro system holds promise for studying the toxicity resulting from long-term exposure to metal ions.

Apoptosis↗
PubMed1990

Improvement of radioactive colloid binding by tumor cells.

Treatment of P388 leukemia cells with poly-DL-lysine (Poly-lys) considerably increases the binding of colloidal chromic phosphate (32P). This augmentation of the number of particles that are bound is in direct relationship with Poly-lys concentration, and very significantly with its degree of polymerization. Treatment with Poly-lys molecular weight 77,000 shows a 100% increase of binding with 200 micrograms and of 50% with 100 micrograms. Poly-lys M.W. 8,000 presents no significant increase, and for the other molecular weights the binding is intermediate.

Adsorption↗
PubMed2002

Comparative microstructural study of the diffusion zone between NiCr alloy and different dental ceramics.

Our knowledge on the bonding mechanisms between the metal and ceramic parts of dental systems is very limited. This work tested the hypothesis that the details of the interface processes can be described in the framework of a chemical diffusion model. The development of interfacial phases was investigated by cross-sectional analytical transmission electron microscopy between a NiCr (Wiron 99) alloy and three different dental ceramics (Carat, Vita VMK 95, and Vision). All systems were investigated at normal firing conditions (suggested by the manufacturer) and at increased firing times as well. The conclusions are based on the results that the formation of a nanocrystalline Cr(2)O(3) layer and amorphous silicon oxide inclusions were detected in the early stage of the firing process in all investigated systems, and that, in the case of Carat and Vision ceramics, formation of complex NiCr and NiCrTi oxides was also observed at longer annealing times.

Chromium Alloys↗
PubMed1978

Diflunisal versus aspirin: a comparative study of their effect of faecal blood loss, in the presence and absence of alcohol.

Faecal blood loss was measured in normal male volunteers using 51Cr-labelled red cells. In a double-blind parallel study in 10 subjects, the effect of 250 mg diflunisal twice daily was compared with 750 mg aspirin 4-times daily. Drugs were taken during two 7-day periods separated by a 1-week control period. Mean daily faecal blood loss during the two treatment periods was 0.32 ml and 0.53 ml in the diflunisal group versus 6.87 ml and 3.20 ml in the aspirin group. Diflunisal did not significantly increase blood loss, while aspirin had a significant effect. In a double-blind crossover study in 12 subjects, the effect of 250 mg diflunisal twice daily was compared with 600 mg aspirin 4-times daily. Alcohol (120 ml, 40%) was added during the last 2 days of each 6-day treatment period. Faecal blood loss was not significantly affected by diflunisal and there was also no significant effect on blood loss when alcohol was co-administered. Aspirin significantly increased faecal blood loss and this effect was significantly enhanced by the addition of alcohol.

Adult↗
PubMed1988

Early stage ovarian cancer: a randomized clinical trial comparing whole abdominal radiotherapy, melphalan, and intraperitoneal chromic phosphate: a National Cancer Institute of Canada Clinical Trials Group report.

Two hundred fifty-seven eligible patients with stage I, IIA "high risk" ovarian carcinoma and IIB, IIIO (disease confined to pelvis), were randomized to either total abdominal radiotherapy (arm A) 2,250 rad in 20 fractions (107 patients), melphalan (arm B) 8 mg/m2/d X 4 every 4 weeks X 18 courses (106 patients), or intraperitoneal chromic phosphate (arm C) 10 to 20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy; arm A, 2,250 rad in ten fractions; and arms B and C, 4,500 rad in 20 fractions. Entry to arm C was discontinued early because of toxicity. In a multifactor analysis using proportional hazards models, no significant difference in survival was observed although there was a marginally significant difference in disease-free survival (P = .015) with arm B being superior to arm A. Stage (P less than .0001), grade (P less than .0001), and histology (P less than .008) were predictors of survival in the multifactor analysis. Performance status, age, and residual disease were significant predictors in the single factor analysis but were not predictive when correction was made for the effects of stage, grade, and histology. Five-year survival rates are 62% for arm A, 61% for arm B, and 66% for arm C. Median duration of follow-up is 8 years. Long-term complications of radiotherapy were seen in 19 patients on arm A, 11 on arm B, and 11 on arm C. Four patients who had received melphalan developed either a myelodysplastic syndrome or acute leukemia. Violations in covering the whole abdominal target volume were correlated with survival.

Chromium↗
PubMed2003

Adjuvant treatment for early ovarian cancer: a randomized phase III trial of intraperitoneal 32P or intravenous cyclophosphamide and cisplatin--a gynecologic oncology group study.

PURPOSE: To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity. MATERIALS AND METHODS: A total of 251 patients were randomly assigned to treatment with 32P or CP. Twenty-two (8.7%) were ineligible following centralized pathology review. Of the 229 patients included in the analysis, 110 received 32P, and 119 received CP. RESULTS: The cumulative incidence of recurrence at 10 years was 35% (95% CI, 27% to 45%) for patients receiving 32P and 28% (95% CI, 21% to 38%) for those receiving CP. Patients receiving CP had a recurrence rate 29% lower than that of those receiving 32P (P =.15, two-tail test). The death rate for patients treated with CP was 17% lower than that for patients treated with 32P (difference not significant). Combining both arms, the 10-year cumulative incidence of recurrence for all stage I patients was 27% (95% CI, 20% to 34%) compared with 44% (95% CI, 32% to 56%) for stage II patients (P =.01). Both regimens were reasonably well tolerated, but problems with inadequate distribution (7%) and small-bowel perforation (3%) make the otherwise less toxic 32P less acceptable. CONCLUSION: Although there are no statistically significant differences in survival, the lower cumulative recurrence seen with CP and complications of 32P administration make platinum-based combinations the preferred adjuvant therapy for early ovarian cancer patients at high-risk for recurrence.

Adenocarcinoma, Mucinous↗
PubMed2003

Intraperitoneal radioactive phosphorus (32P) versus observation after negative second-look laparotomy for stage III ovarian carcinoma: a randomized trial of the Gynecologic Oncology Group.

PURPOSE: The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy. PATIENTS AND METHODS: In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98). RESULTS: With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P =.27). There was no statistically significant difference in OS (P =.19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group. CONCLUSION: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.

Adult↗
PubMed2005

Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.

Evidence suggests that chromium supplementation may alleviate symptoms associated with diabetes, such as high blood glucose and lipid abnormalities, yet a molecular mechanism remains unclear. Here, we report that trivalent chromium in the chloride (CrCl3) or picolinate (CrPic) salt forms mobilize the glucose transporter, GLUT4, to the plasma membrane in 3T3-L1 adipocytes. Concomitant with an increase in GLUT4 at the plasma membrane, insulin-stimulated glucose transport was enhanced by chromium treatment. In contrast, the chromium-mobilized pool of transporters was not active in the absence of insulin. Microscopic analysis of an exofacially Myc-tagged enhanced green fluorescent protein-GLUT4 construct revealed that the chromium-induced accumulation of GLUT4-containing vesicles occurred adjacent to the inner cell surface membrane. With insulin these transporters physically incorporated into the plasma membrane. Regulation of GLUT4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, and Akt. Consistent with a reported effect of chromium on increasing membrane fluidity, we found that chromium treatment decreased plasma membrane cholesterol. Interestingly, cholesterol add-back to the plasma membrane prevented the beneficial effect of chromium on both GLUT4 mobilization and insulin-stimulated glucose transport. Furthermore, chromium action was absent in methyl-beta-cyclodextrin-pretreated cells already displaying reduced plasma membrane cholesterol and increased GLUT4 translocation. Together, these data reveal a novel mechanism by which chromium may enhance GLUT4 trafficking and insulin-stimulated glucose transport. Moreover, these findings at the level of the cell are consistent with in vivo observations of improved glucose tolerance and decreased circulating cholesterol levels after chromium supplementation.

3T3-L1 Cells↗
PubMed1997

Wormy wood?

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Arsenates↗
PubMed1989

Induction of lipid peroxidation in mice by hexavalent chromium and its relation to the toxicity.

Comparative effects of hexavalent (K2Cr2O7:Cr(VI)) and trivalent chromium (Cr(NO3)3:Cr(III)) on the development of lipid peroxidation, and the relationship between the lipid peroxidation and damage to tissues were studied using male ddY strain mice. The animals were administered with either of two chemicals at a dose of 20 mg Cr/kg by a single intraperitoneal injection. The results obtained were as follows: (1) Lipid peroxidation in the liver, as measured by the synthesis of thiobarbituric acid reactive substances (TBARS), showed a significant increase at 24 and 48 hr after Cr(VI) injection, while in the kidney it was observed only at 48 hr. In the mice administered with Cr(III), TBARS formation in the liver went down below the control levels, while no change was observed in the kidney. (2) Chromium contents in the liver and kidney showed a maximum level at 6 hr after injection of Cr(VI) and then those declined to the half of the maximum level at 48 hr, respectively. Chromium contents in the liver and kidney of the mice injected with Cr(III) were lower than those injected with Cr(VI) during the experimental period. (3) Increases of TBARS formation in the liver, chromium content in the liver and kidney, and ornithine carbamyl transferase (OCT) activity indicative of the liver cell damage, and urea nitrogen content in the serum, indicative of the kidney damage, observed at 24 hr after injection of Cr(VI) were inhibited by simultaneous injection of 100 mg/kg of L-ascorbic acid, as antichrome agent, respectively. These observations might suggest a possible causative role of lipid peroxidation in Cr(VI) toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Pharmacotherapy of type 2 diabetes mellitus.

OBJECTIVE: To review the drug treatments and some of the popular, nontraditional remedies now available for type 2 diabetes mellitus, as well as selected investigational agents; to describe each medication's place in the overall approach to treatment. DATA SOURCES: English-language journals, abstracts, review articles, and newspaper accounts. DATA SYNTHESIS: In the past five years, there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes. Several new agents have entered the clinical arena, and many more are in the late stages of investigation leading to approval. Sulfonylureas stimulate the production and release of insulin; these drugs must be used in patients with an intact pancreas. The meglitinides are nonsulfonylurea agents that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide appears to require the presence of glucose to close the adenosine triphosphate-sensitive potassium channels and induce calcium influx. Metformin reduces hepatic glucose production in some patients and increases peripheral glucose utilization, but its use is hampered by a high percentage of adverse reactions. Disaccharidase inhibitors effectively compensate for the defective early-phase insulin release by slowing the production of sugars from carbohydrates. Thiazolidinediones appear to activate peroxisome proliferator-activated receptor gamma, which is involved in the metabolism of lipids. Short-acting insulin and the role of weight-loss agents are also discussed. CONCLUSIONS: The availability of new options for diabetes therapy provides a chance for successful therapy in a larger number of patients. However, it is important to consider how much true benefit these new forms of treatment will have on the diabetic community. The best choice for a patient remains controversial.

Anti-Obesity Agents↗
PubMed2005

Effects of a combination of niacin and chromium(III)-chloride on the skin and lungs of hyperlipemic rats.

The aim of this study was to investigate the biochemical effects of niacin and chromium(III)-chloride on serum lipid peroxidation, uric and sialic acids, and the extent of lipid peroxidation and glutathione levels in skin and lung tissues of hyperlipidemic rats. In this study, female Swiss albino rats, 12 mo old, were used. They were randomly divided into four groups. Group I animals were fed with a standard pellet diet and water ad libitium. Group II rats were fed with a standard pellet diet and were treated with a dose of 250 microg/kg body weight CrCI(3).6H(2)O and 100 mg/kg body weight niacin, for 45 d, by the gavage technique. Group III rats were fed a lipogenic diet in which 2% cholesterol, 0.5% cholic acid, and 20% sunflower oil were added to the pellet chow. In addition, the animals in this group drank water containing 3% ethanol. This regime was maintained for 60 d. The rats in group IV were maintained in the same food and drink regime as the animals in group III. After 2 wk, the animals showed symptoms of hyperlipemia and they were treated with 250 microg/kg body weight CrCI(3).6H(2)O and 100 mg/kg body weight niacin, by gavage, for 45 d. On d 60, the blood and the skin and lungs samples were taken from animals. In the hyperlipemic groups, a reduction of the lung glutathione level and an increase in serum, lung, and skin lipid peroxidation levels and in serum sialic and uric acid were observed. In rats treated with a combination of niacin and Cr(III), the skin and serum lipid peroxidation and the sialic and uric acid levels decreased while showing an increase of lung glutathione activity. These results suggest that niacin and Cr(III), when administered in combination, have a protective effect against skin and lung tissues damage as a result of hyperlipidemia.

Animals↗
PubMed2002

Endotoxin decreases 51CrCl3 uptake in early weaned pigs.

Endotoxin, a product of bacterial infections, was used to investigate the effects acute infections on chromium (Cr) uptake in early weaned (14 d of age) pigs. At d 18, pigs were anesthetized, and a 2-mm silastic jugular catheter was inserted and passed subcutaneously to a dorsal position behind the ear. At d 21, pigs were deprived of food for 7 h and injected intraperitoneally with saline or 25 microg endotoxin (lipopolysaccharide from Escherichia coli serotype 0111:B4) per kg body wt suspended in 9 g/L saline. One hour after dosing, an oral dose of 0.7 mCi of 51CrCl3 was given by micropipet. Blood was sampled from the catheter at intervals until necropsy at 8 h after the 51CrCl3 dose. Blood and tissue samples were counted in a gamma counter. 51Cr in blood was significantly lower at 3, 4, 5, 6, and at 8 h after dosing in endotoxin-injected pigs compared to controls. Eight hours after 51CrCl3 dosing, 51Cr retention was significantly lower in the liver, heart, and kidney in endotoxin-treated pigs and tended to be lower in spleen (p<0.06) and in urine (p<0.16) with endotoxin treatment. These data suggest that during acute infection, there might be decreased Cr uptake and retention.

Animals↗
PubMed2002

Effects of dietary chromium chloride supplementation on performance, some serum parameters, and immune response in broilers.

This study was conducted to investigate the effect of increasing dietary levels of inorganic chromium (CrCl3 x 6H2O) on the performance, blood chemistry, and immune response of broilers. Eighty newly hatched Ross PM3 broiler chicks were evenly distributed to five groups of 16 chicks each. Two groups (control and only sheep red blood cell inoculated) were fed the basal diet containing 2.2 and 4.5 mg Cr/kg and the remaining groups were fed 20, 40, or 80 mg/kg Cr-supplemented diets for 44 d. Chicks in all groups, except in the control, at 3 and 5 wk of age, were injected intraperitonally with sheep red blood cell for determining the primary and secondary antibody responses, respectively. When the chicks were 4 wk of age, a delayed-type hypersensitivity test was performed. White blood cells were differentiated. Blood samples were collected for the determination of serum proteins, glucose, cholesterol, cortisol, minerals, and alkaline phosphatase activity and for antibody response. Chromium had no effect on weight gain, but 20 mg/kg supplemental Cr resulted in 18.57% reduction in feed consumption and improved feed efficiency by 16.77%. Chromium did not affect serum cholesterol and P levels but reduced serum glucose and increased serum protein, Cr, Ca, and Mg levels, and ALP activity. A slight reduction was observed with Cr supplementation in cortisol levels. Slight but not significant increases were observed with Cr in serum Zn and Cu. Chromium increased the ratio of bursa of Fabricius and liver to body weight. Heterophil and monocyte counts and heterophil/lymphocyte ratio were reduced and lymphocyte counts, total antibody, IgG, and IgM titers were increased by supplemental Cr. All levels of Cr increased the cell-mediated response to phytohemagglutinin. No alterations in tissues were observed by histopathological examinations.

Animal Feed↗