Effects of iron supplementation and discontinuation on serum copper, zinc, calcium, and magnesium levels in women

The purpose of this study was: 1) to establish the prevalence of depleted iron stores, iron deficiency, and low serum levels for copper, zinc, calcium, and magnesium in a healthy female population; and 2) to examine the effects of iron supplementation and discontinuation on the serum levels of the above minerals. One hundred eleven healthy women between the ages of 18 and 40 yr reported for fasted morning blood sampling for iron, copper, zinc, calcium, and magnesium status. Forty-five subjects were either iron-deficient as defined by a hemoglobin level below 120 g.l-1 (four subjects) or iron deplete as defined by a serum ferritin value below 20 micrograms.l-1 (43 subjects). Two subjects fit both criteria. This subgroup continued with the study and were prescribed a normal therapeutic iron dose (320 mg elemental iron per day, taken as two Slow-Fe tablets.d-1 for a period of 12 wk). The subjects then discontinued the iron supplementation for a further 12 wk. The response of the various blood minerals was monitored at 6-wk intervals. Twenty-five subjects completed the full 24-wk treatment. The main conclusions to be made from this study were that: 1) For this sample population of women, iron depletion was quite common (39%), although low hemoglobin values (< 120 g.l-1) were only seen in 3.6%. No subjects fell below the criteria for low serum copper levels (< 13.3 mumol.l-1) nor low serum magnesium levels (< 0.6 mmol.l-1). Seven subjects (6.5%) fell below the criteria for low serum zinc levels (< 11.5 mumol.l-1) while two subjects (1.8%) were below the criteria for low serum calcium levels (< 2.20 mmol.l-1). 2) Therapeutic oral iron supplementation was successful in raising mean serum ferritin values from 15.9 micrograms.l-1 to 36.5 micrograms.l-1 but was not associated with decrements in serum copper or calcium levels. 3) The treatment did not significantly effect serum zinc and magnesium levels during the supplementation period, but a downward trend continued through the discontinuation phase so that at 18 and 24 wk serum zinc and magnesium levels were significantly lower than baseline. 4) Oral contraceptive use was associated with elevated serum copper and ferritin values and lowered serum magnesium levels.     

The trans-syn-I thymine dimer bends DNA by approximately 22 degrees and unwinds DNA by approximately 15 degrees

Chromium metabolism of lactating women was evaluated by measuring diet, breast milk, urine, and serum chromium in 17 subjects 60 d postpartum. Breast milk chromium concentration was similar for the 3 d of collection with a mean +/- SE concentration of 3.54 +/- 0.40 nmol/L (0.18 ng/mL). Dietary intake and urinary chromium values were also similar for each of the 3 collection days. Total chromium intake of lactating mothers (0.79 +/- 0.08 mumol/d) was greater than that of reference female subjects (0.48 +/- 0.02). There was a significant correlation (r = 0.84) between serum chromium and urinary chromium excretion. If a breast milk volume of 715 mL is assumed, chromium intake of exclusively breast-fed infants is < 2% of the estimated safe and adequate daily intake of 10 micrograms. In summary, breast milk chromium content is independent of dietary chromium intake and serum or urinary chromium values. Chromium intake also did not correlate with serum or urine chromium but there was a significant relationship between serum and urinary chromium concentrations.     

Effects of trace element and/or vitamin supplementation on vitamin and mineral status, free radical metabolism and immunological markers in elderly long term-hospitalized subjects. Geriatric Network MIN. VIT. AOX

A randomized double-blind trial was performed in order to assess the efficacity of differing combinations of antioxidant nutrients on biochemical parameters of vitamin and trace element status, immunological parameters and free radical metabolism in elderly long term hospitalized subjects. A total of 756 institutionalized elderly subjects were recruited in 26 nursing homes in different areas of France. Four groups were constituted, receiving daily, for 1 year, either vitamins (beta-carotene, 6 mg; vitamin C, 120 mg; and vitamin E, 15 mg), trace elements (zinc, 20 mg and selenium, 100 micrograms), trace elements associated with vitamins, or a placebo. Biochemical indicators of trace elements and vitamin status and free radical parameters were measured before and after 6 months and 1 year of supplementation. Some immunological markers were investigated initially and after 6 months of supplementation on a subsample of 134 subjects. Mean plasma levels of alpha-tocopherol, gamma-tocopherol, vitamin C, alpha-carotene, beta-carotene and copper increased significantly after 6 months of supplementation in groups receiving vitamins alone or associated with trace elements. Serum selenium concentrations were significantly increased at 6 months of supplementation, and serum zinc only after one year in the trace element groups. Serum lycopene levels were significantly decreased by trace element supplementation. A significant increase in Se-glutathione peroxidase (GPx) levels was observed in groups receiving trace elements alone or associated with vitamins. No effect was noted on superoxide dismutase (SOD) activity or TBARs production. No effect of supplementation was found for in vitro lymphocyte proliferative responses or most lymphocyte subsets, except for a significantly lower percentage of CD2 subsets observed in groups receiving mineral supplementation either alone or associated with vitamins. A significant difference in CD19 subsets was found in groups receiving trace elements. Mean IL-1 production was significantly higher after 6 months of supplementation in the vitamin groups.     

Hereditary nephritis and the heart

Twelve women (23-34 yr), comprising a bed-rest (BR) group of eight subjects and an ambulatory (AMB) group of four subjects, were centrifuged after 14 days of ambulatory control (C),after 15 days of a 17-day BR period, and on the third day of recovery (R). Venous blood was taken before and after the third +3.0 G acceleration run (1.8 G/min). Relative to (C), the +Gz tolerance after BR was reduced -49.0% (P less than 0.05) in the BR group and -38.7% (NS) in the AMB group; during (R) the BR group regained up to 89.4% and the AMB group up to 87.1% of their (C) tolerances. In each of the three test periods, the shifts in plasma Na, Cl, PO4, and osmotic contents, which accompanied +Gz, followed the outward shift of plasma volume (PV). The correlation of the shift of PV during acceleration with the +Gz tolerance was 0.72 (P less than 0.01). During acceleration, the PV and electrolyte loss for both groups after BR was about half the loss of (C) and (R). Compared with (C) and (R) values, potassium shifts were variable but the mean corpuscular volume and mean corpuscular Hb contents and concentrations were unchanged during all +Gz runs; The results indicate that: 1) the higher the (C) + Gz tolerance, the greater the tolerance decline due to BR; 2) relative confinement and reduced activity contribute as much to the reduction in tolerance as does the horizontal body position during BR; 3) bed-rest deconditioning has no effect on the erythrocyte volume during +3.0 Gz; and 4) about one-half the loss in tolerance after BR can be attributed to PV and electrolyte shifts.     

beta-Endorphin and adrenocorticotrophin after incremental exercise and marathon running--female responses

Investigations of exercise-induced increases in beta-endorphin, adrenocorticotropic hormone (ACTH) and cortisol concentration have been carried out mainly in men. Data concerning the female reaction are sparse and less clear. In a comparison between incremental exercise and marathon running 14 experienced female marathon runners volunteered to run to exhaustion according to an incremental treadmill protocol. They ran a marathon 4 weeks later. Blood was analysed for beta-endorphin, ACTH and cortisol concentration immediately prior to the laboratory treadmill test, 3, 30 and 60 min later, as well as prior to the marathon, after 60 min and 120 min of running and 3, 30 min, and 24 h after completion of the run. At each blood collection, lactate concentration, heart frequency and perceived exertion were determined. The mean marathon running time was 3.22 h. Baseline concentrations for beta-endorphin of 22 pmol.l-1 before the marathon and 19 pmol.l-1 before the treadmill exercise increased 1.4-fold 30 min after the marathon and 1.9-fold after the treadmill exercise; for ACTH the baseline of 4.7 and 4.0 pmol.l-1 was increased by 8.3- and 10.3-fold, respectively. Cortisol concentration rose exponentially from a baseline 17 micrograms.dl-1 and peaked at 2.2-fold 30 min after the run, when the maximal concentration also had been reached after the treadmill test, increasing 1.3-fold from a baseline of 21 micrograms.dl-1. The maximal values for cortisol concentration after both exercises differed from each other, while the maxima of ACTH and beta-endorphin concentrations were similar. The ACTH and beta-endorphin concentration declined more slowly during the recovery after the marathon than after the treadmill. Cortisol concentration was below baseline 24 h later. In comparison with men studied earlier, female marathon runners showed higher baseline concentrations and lesser increases in beta-endorphin and lower baseline concentrations and larger increases in ACTH concentration after both types of exercise. The delayed decrease in concentration of the hormones after the marathon was similar in male and female runners.     

Trace element and vitamin concentrations and losses in critically ill patients treated with continuous venovenous hemofiltration

OBJECTIVES: To measure the blood concentrations of a number of trace elements and vitamins in critically ill patients and examine their elimination by continuous venovenous hemofiltration (CVVH). SETTING: Intensive care unit of a tertiary institution. DESIGN: Prospective, controlled, clinical study. PATIENTS: Eight critically ill patients requiring renal replacement therapy, nine patients requiring intensive care treatment but not requiring renal replacement therapy, and nine healthy controls. INTERVENTIONS: Measurement of trace element and vitamin concentrations in blood and ultrafiltrate. MEASUREMENTS AND MAIN RESULTS: Compared with normal volunteers, critically ill patients requiring CVVH had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. During the first 24 hrs of CVVH, there were no changes in the trace element and vitamin concentrations in blood, nor were there differences between pre- and postfilter samples. Micronutrient losses in the ultrafiltrate were small or undetectable except for Vitamin C, chromium, and copper. Compared with normal volunteers, critically ill patients not requiring CVVH also had significantly lower median blood concentrations of vitamin C, vitamin E, selenium, and zinc. There were no differences between the two critically ill groups. CONCLUSIONS: The clinical significance of the reductions in blood concentrations of selenium, zinc, vitamin C, and vitamin E in critically ill patients and the ultrafiltrate losses of Vitamin C, copper, and chromium remains unclear.     

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.     

Serum calcium, magnesium, copper and zinc and risk of cardiovascular death

OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality. DESIGN: A nested case-control study within a prospective population study. SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.     

Serum concentrations of zinc and copper in bull terriers with lethal acrodermatitis and tail-chasing behavior

OBJECTIVE: To establish similarities or differences in tissue concentrations of zinc, copper, and iron in Bull Terriers with lethal acrodermatitis (LAD) and tail-chasing behavior (TCB) and to confirm the suspicion that copper is involved in the etiopathogenesis of LAD. SAMPLES: Serum samples from 29 Bull Terriers (9 control dogs, 6 dogs with LAD, 14 dogs with TCB), and liver and kidney specimens from 2 dogs and 1 and 4 dogs with LAD or TCB, respectively. PROCEDURE: Serum, liver, and kidney mineral (zinc, copper, and iron) concentrations in Bull Terriers with LAD or TCB and in a group of control dogs were analyzed, using flame atomic absorption after wet ashing technique. RESULTS: Serum zinc and copper concentrations were lower (P < 0.05) in dogs with LAD, compared with values for control dogs and dogs with TCB. Liver zinc and copper concentrations were similar to serum values. Kidney zinc and copper concentrations were similar among the 3 groups. Serum, liver, and kidney iron concentrations had a wide range of variability within all 3 groups. CONCLUSION: Copper deficiency is associated with LAD. The primary cause of LAD may be copper deficiency, with zinc involved secondarily, or combined zinc and copper deficiencies. The role of ion deficiency in TCB was not clarified. CLINICAL RELEVANCE: Serum zinc and copper concentrations should be determined when LAD is suspected.     

Alaskan malamute chondrodysplasia IV. Concentrations of zinc, copper and iron in various tissues

Trace mineral concentrations in various tissues of the chondrodysplastic (dwarf) Alaskan Malamute are remarkably different as compared to normal. The zinc level in heart tissue was depressed in dwarf animals (26 weeks). Copper concentration in the liver is elevated two to four fold in 26 week old dwarf animals and iron levels are significantly elevated in kidney, liver and pancreas of these animals. These observations suggest that the dwarf Alaskan Malamutes suffer from a genetic defect in trace mineral metabolism. If this is the case, then many of the skeletal lesions reported for these animals may be attributed to disorders in either zinc or copper metabolism.     

Coronary blood flow during +Gz stress in +Gz conditioned adult miniature swine

Four female adult miniature swine were acceleration conditioned for a period of 1 month using repeated acute exposure to simulated aerial combat maneuver profiles which exposed the animals to an average of +4.5G, for 106s. This period of conditioning produced adaptation as evidenced by decreased maximal heart rates during +Gz and by the absence of any +Gz induced gross cardiac pathology. Coronary blood flow was measured in these conditioned animals with the radiolabeled microsphere technique. Blood flows were measured under resting conditions, during 60s exposures to +3Gz and +5Gz and 10 min after +5Gz exposure. Coronary flow was increased 2-3 fold during +3Gz and +5Gz. The regional distribution of coronary blood flow during +Gz was similar to that under resting control conditions. There were no significant differences between coronary blood flows during +Gz in these conditioned animals and the values previously reported from the initial exposure of miniature swine to similar levels of +Gz. These results indicate that 1 month of acceleration conditioning of the types used in these studies has no significant effect on the response of coronary blood flow to +3Gz and +5Gz stress.     

Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane association of sucrose synthase: changes during the graviresponse and possible control by protein phosphorylation

Mean manganese superoxide dismutase (Mn-SOD) concentrations in the serum of patients suffering from alcohol dependence is almost twice as high as in serum of non-dependent controls. In order to investigate the time course of this parameter during abstinence, we determined it at different time points. Patients had mean Mn-SOD serum concentrations (+/-S.D.) of 150.4 +/- 76.3, 121.1 +/- 40.7, 94.6 +/- 37.8 micrograms/ml at 1, 10 and 40 days after abstinence compared to 76.3 +/- 16.9 micrograms/ml as mean Mn-SOD value in the control group. Although the Mn-SOD concentration tended to normalise during abstinence, the differences between index and control group remained significant up to the last measurement at day 40.     

Granisetron, a new and potent antiemetic for treatment of cytostatic drug-induced vomiting in gynecological malignancies

To study the effects of positive acceleration on the plasma atrial natriuretic peptide (ANP) and renin concentration (PRC), students of the Korean Air Force Academy and pilots were exposed to +6 Gz for 30 s in a human centrifuge without anti-G suits. An acceleration to +6 Gz caused a significant increase (p < 0.01) in the heart rate of both the student and pilot groups. We performed blood collection within 2 min after terminating centrifugation. Systolic blood pressure was increased significantly (p < 0.01), and heart rates were elevated and did not return to control levels by 2 min after centrifugation. Plasma ANP decreased significantly in both groups (p < 0.05). The difference in the percentage of ANP decrement was not significant between student and pilot groups. PRC increased significantly (p < 0.05) in both groups. This study demonstrated that high +Gz exposure in man caused a significant reduction of plasma ANP concentration, although PRC, heart rate, and blood pressure increase.     

Diltiazem concentrations in plasma vs PR intervals on electrocardiogram in 8 men

AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model.     

Daily dietary intake of copper, zinc, and selenium of exclusively breast-fed infants of middle-class women in Burundi, Africa

Copper (Cu), zinc (Zn), and selenium (Se) in human milk of middle-class Burundian women during the first 10 mo of lactation have been determined. Wet acid digestion, using nitric and perchloric acids, and atomic absorption spectrometric analysis have been used. Daily intakes have been calculated and proven to decrease from 0.39 +/- 0.05 (colostrum) to 0.16 +/- 0.02 (mature milk), 2.3 +/- 0.3 (colostrum), to 1.2 +/- 0.2 mg (mature milk) and 10.9 +/- 1.5 (colostrum) to 5.3 +/- 0.8 micrograms (mature milk) for Cu, Zn, and Se, respectively. Since values for this African country are nonexistent, intake levels are compared with literature data and found to be somewhat higher than those observed in other poorly nourished countries. The recommended safe and adequate daily intake for infants of 0-6 mo of age, as proposed by the National Research Council of the USA, is only met for Burundian infants < 1 mo of age. The function of copper (Cu) and zinc (Zn) as essential trace elements has been known for quite a number of years (1). Also, selenium (Se) is a trace element essential for the activity of glutathione peroxidase (2) and type I iodothyronine 5-deiodinase (3). For all three elements, an adequate intake is necessary for satisfactory infant growth and development (4). In view of the almost total lack of relevant data on Burundi (Africa), we have determined Cu, Zn, and Se in human milk of middle-class Burundian women during the first 10 mo of lactation (5). The aim of this study is to assess infants' elemental intake for this country and compare this with literature data on trace elemental intake of exclusively breast-fed infants.     

Lack of association between copper, zinc, selenium and blood pressure among healthy children

Contradictory results have been published about the relation between copper, zinc and selenium and blood pressure (BP). To evaluate the role of these trace elements in BP regulation, we analysed the correlations between BP and copper, zinc and selenium, measured from serum, diet and hair among 3596 healthy children in a 6-year follow up. Fasting blood samples were used in serum copper, zinc and selenium analyses. The dietary intake of trace elements and energy were determined by the 48-h recall method. The hair copper and zinc analyses were performed from the naturally coloured hair samples. Correlation analysis was used to show the relation between BP and copper, zinc or selenium in each study year and during a 3- or 6-year follow-up period. The zinc-to-copper ratio in serum, diet and hair was calculated. In the correlation analyses the data was adjusted for weight and the daily intake of energy. Neither serum and diet copper or zinc, nor the zinc-to-copper ratio correlated uniformly with BP measured in the same year (correlation coefficients varying from -0.12 to 0.18) or in the subsequent years. Hair copper and zinc correlated weakly negatively with BP (correlation coefficients varying from -0.17 to -0.01). Serum selenium correlated weakly positively with systolic and diastolic BP measured in the same year (correlation coefficients varying from 0.03 to 0.14), but not with subsequent BP measured in the second or third survey. Dietary selenium had an inconsistent effect on BP (correlation coefficients varying from -0.14 to 0.26). In conclusion, copper, zinc, their ratio or selenium did not associate with BP, nor did they have any effect on subsequent BP.     

Relationship between acute diarrhoea and low plasma levels of vitamin A and retinol binding protein

OBJECTIVE: We studied possible sex differences of the effect of fenofibrate on serum lipoproteins. Twenty-three patients with primary hypercholesterolaemia (10 postmenopausal women and 13 aged-matched men) were treated with slow-release fenofibrate for 96 weeks. RESULTS: Steady state lipoprotein concentrations were reached after 12 and 24 weeks of treatment in women and men, respectively. During the subsequent follow-up the lipoprotein concentrations remained constant. In women total and low-density lipoprotein (LDL) cholesterol decreased from 299 to 234 mg.dl-1 and from 210 to 151 mg.dl-1, respectively, and in men from 265 to 233 mg.dl-1 and from 192 to 160 mg.dl-1. The decrease in triglycerides was also more pronounced in women (-42%) than in men (-18%). High-density lipoprotein (HDL) cholesterol increased significantly in women from 53 to 63 mg.dl-1 but not in men (45 to 50 mg.dl-1). Since the changes in LDL and HDL cholesterol occurred in opposite directions, the decrease in LDL/HDL cholesterol ratio was accentuated in both groups. However, this ratio was decreased almost twofold in women (-41%) compared to men (-23%). Although the serum concentrations of fenofibric acid were 1.3-fold higher in women than in men, which was probably due to the higher body weight in men (1.2-fold), this difference can hardly explain the favorable effect on lipoproteins in women. CONCLUSION: The present study indicates that fenofibrate might be very effective by reducing the concentrations of atherogenic lipoproteins in postmenopausal women.     

Effects of the combination of ketoconazole and calmodulin inhibitors against Candida albicans in vitro. Short communication

The susceptibility of 66 strains of Candida albicans from patients was tested against ketoconazole (Ktz), chlorpromazine (Chl) levomepromazine (Lev), haloperidol (Hal) and the combination of Ktz with these calmodulin inhibitors, using Sabouraud's broth. The minimal inhibitory concentrations (MICs) for 66 strains of C. albicans were as follows: Chl 192 +/- 11.4 micrograms/ml, Lev 306 +/- 16.4 micrograms/ml, Hal 464 +/- 13.8 micrograms/ml compared with Ktz 34.46 +/- 3.9 micrograms/ml. The combination of Ktz and calmodulin inhibitors in various ratios (1:1,1:2,2:1) was found to exert synergistic effect and the mean values of the combinations were: Ktz+Chl 3.45 +/- 0.35, 3.78 + 0.36, 5.58 + 0.4 micrograms/ml; Ktz+Lev 10.8 +/- 2.19, 9.7 +/- 2.23, 10.5 + 2 micrograms/ml; Ktz+Hal 6.4 +/- 1.7, 6.8 +/- 1.6, 7.28 +/- 1.5 micrograms/ml. These results were significantly different (p < 0.001) from those of ketoconazole. These findings indicate that some calmodulin inhibitors increase the antifungal activity of Ktz against C. albicans in vitro.