Influence of highly concentrated fluoride dentifrices on remineralization characteristics of enamel in vitro.

OBJECTIVES: The aim of this in vitro study was to evaluate the role of highly fluoridated dentifrice on remineralization characteristics of lowly and highly pre-demineralized enamel artificial caries lesions. METHODS: Bovine enamel specimens were prepared (pH 4.95; 21 days) and discriminated in either lowly [L] or highly [H] pre-demineralized artificial caries lesions. Specimens with a mean ΔZbaseline,L (95% CI) of 5120 (4995; 5245) vol.% × µm and a mean ΔZbaseline,H of 8187 (8036; 8339) vol.% × µm were selected and randomly allocated to 12 groups (n = 20). Treatments during pH-cycling (28 days; 6 × 60 min demineralization/day) were brushing 2×/day with fluoride-free (0 ppm F- [L0/H0]), 1100 ppm F- [L1100/H1100], 2800 ppm F- [L2800/H2800], 5000 ppm F- [L5000/H5000], 5000 ppm F- + glycerin [L5000 + glycerin/H5000 + glycerin], and 5000 ppm F- + TCP [L5000 + TCP/H5000 + TCP] containing dentifrices. Dentifrice slurries were prepared with deionized water (1:3wt/wt). After cycling specimens presenting lesion surface loss were discarded and for the remaining 202 specimens, transversal microradiographic (TMR) analyses (ΔZpH-cycle/LDpH-cycle) were performed again. Changes in mineral loss (ΔΔZ = ΔZbaseline - ΔZpH-cycle) and lesion depth (ΔLD = LDbaseline - LDpH-cycle) were calculated. RESULTS: Significant differences for ΔΔZ could be found between L0, L1100, and L5000 as well as H0, H1100, and H2800/H5000 (p ≤ 0.01; ANCOVA). Except for 0 ppm F-, higher ΔΔZ could be found in highly compared with lowly demineralized specimens (p ≤ 0.004; ANCOVA). After pH-cycling, a second lesion front could only be observed in H5000 and H5000 + TCP. The correlation between ΔΔZ and F- was moderate for lowly and highly demineralized lesions (rL = 0.591; pL < 0.001; rH = 0.746; pH < 0.001), indicating a fluoride dose response for both. CONCLUSION: For both baseline substrate conditions, a dose response for fluoride could be revealed. CLINICAL SIGNIFICANCE: Remineralization characteristics of enamel directly depended on baseline mineral loss.

[Preventive bone mineral density measurement in postmenopausal women. Differentiation of treatment of recommendations Guidelines of the Umbrella Organization for Osteology ("Dachverband Osteologie")]. / Präventive Knochendichtemessung bei postmenopausalen Frauen. Differenzierung der Therapieempfehlungen der Leitlinien des Dachverbandes Osteologie (DVO).

BACKGROUND: Osteopenia (OP) or osteoporosis (OST) was diagnosed by bone densitometry (DXA) in postmenopausal women free of known skeletal disorders and without acute fracture. DVO guidelines were applied to define therapeutic indication. METHODS: The study included 94 women aged 59-81 years. Fracture or operation ≤12 months, malignant tumor, ovariectomy, and drugs such as cortisone, strontium, fluorides, bisphosphonates, SERMs, estrogens, and steroids were exclusion criteria. The lowest T-score at the spine, femoral neck, or total hip was decisive. The indication for therapy was determined by evaluating age, BMD, and other risk factors. RESULTS: Using the WHO criteria 22.3% (n=21) had normal BMD, 52.1% (n=49) had OP, and 25.6% (n=24) had OST. According to "Dachverband Osteologie" (DVO) guidelines, 28 women (29.8%) of the whole group needed therapy. Of the 28 women receiving therapy, 9 had OP and 19 had OST. Therapy was indicated in 18.4% for OP and 79.2% for OST. CONCLUSION: A preventive measurement of BMD with DXA provides a benefit for postmenopausal women. Combinatory assessment and consideration of other risk factors allows identification of women who might benefit from early treatment.

Adipokine expression in brown and white adipocytes in response to hypoxia.

BACKGROUND: Adipose tissue has emerged as an important endocrine regulator by secreting hormones referred to as adipokines. Recent studies showed that adipose tissue considerably responds to hypoxia. Although the impact of white adipose tissue on regulative processes is established, the importance of brown adipose tissue in adults has emerged just recently. METHODS: Brown (BA) and white adipocytes (WA) were cultured either in the presence of chemical hypoxia-mimetics or under hypoxic atmosphere of 1% oxygen. Expression of hypoxia-inducible factor 1α (HIF- 1α) was assessed by western blot. The expression levels of several known HIF-1α-regulated proteins [vascular endothelial growth factor (VEGF), leptin, adiponectin, and angiotensinogen (AGT)] were quantified. RESULTS: Both chemical hypoxia-mimetics and physical hypoxia led to increased nuclear HIF-1α expression and to decreased cytoplasmatic adiponectin in both cell types. In contrast, VEGF and AGT expression did not change upon hypoxic stimulation. Leptin was exclusively detectable in WA, while uncoupling-protein 1 (UCP-1) was expressed in BA only. CONCLUSIONS: WA and BA are sensitive to hypoxia, in which HIF-1α expression is induced. Protein expression of adiponectin is hypoxia-dependent, whereas AGT, VEGF, leptin, and UCP-1 expression do not change secondary to hypoxia.

Effect of Arthrospira powders from different producers on the formation of endothelial cell monolayers.

Arthrospira platensis (AP) and some of its derived products have well-established biological activities as antioxidants or as agents to reduce cardiovascular disease risk factors. Furthermore, AP products have gained increasing importance as potential anti-cancer agents. However, the ingredients of the available products vary greatly with the origin, the type of production and processing, which could have significant consequences for their biological effects. Therefore, the composition and biological influence of five distinct AP powders, which were acquired commercially or produced at a public biotechnology institute, were investigated in regard to their endothelialization capacity using a cell impedance- (CI) based measurement method. The study revealed that the AP composition and especially the influence on HUVEC proliferation differed significantly between the five AP powders up to 109%.Thus, it could be shown that the method used allows the reliable detection of quantitative differences in biological effects of different AP preparations.

[Preoperative iron deficiency with/without anemia-an underestimated risk factor?] / Präoperativer Eisenmangel mit/ohne Anämie ­ ein unterschätzter Risikofaktor?

BACKGROUND: Every third surgical patient already suffers from anemia before surgery. The main cause is iron deficiency. OBJECTIVE: This article describes the perioperative risk of iron deficiency with/without anemia and summarizes potential preventive measures. MATERIAL AND METHODS: Presentation of various current original papers, guidelines and own experiences from the German patient blood management network. RESULTS AND CONCLUSION: Preoperative iron deficiency with/without anemia is an underestimated risk factor for perioperative complications. The implementation of preoperative diagnostics and treatment as part of a comprehensive patient blood management reduces complications and increases patient safety.

Vitamins are associated with survival in patients with end-stage renal disease: a 4-year prospective study.

BACKGROUND: Patients with end-stage renal disease are at high risk from premature death due mainly to cardiovascular disease and infections. Established risk factors do not sufficiently explain this increased mortality. We, therefore, investigated total mortality prospectively in a single-centre study in patients on hemodialysis and assessed the prognostic value of baseline disease status, laboratory variables including emerging risk factors, and the influence of vitamin treatment. METHODS: Patients (n = 102) were followed-up for 4 years or until death (n = 49). Survival was calculated by the Kaplan-Meier method. Cox-proportional hazards model was used to determine independent predictors of total mortality. RESULTS: The known risk factors age, baseline clinical atherosclerotic disease, low albumin and increased cardiac troponin T were significantly associated with mortality. Patients who received multivitamins during follow-up had a significantly lower mortality risk than those not receiving this treatment (hazard ratio 0.29, 95% confidence interval 0.15-0.56). These associations remained significant after adjustment for age, cardiovascular disease, albumin and cardiac troponin T at baseline. CONCLUSIONS: The present study suggests that multivitamin supplementation in patients with end-stage renal disease is closely associated with reduced mortality due to all causes. These observations have to be validated in randomized clinical intervention trials.

Post-hoc analysis on the CD14 C(-260)T promoter polymorphism and coronary heart disease.

Functional C(-260)--> T polymorphism in the promoter of the CD14 gene has been reported to be associated with coronary heart disease (CHD). The functional role of the polymorphism, however, is still a matter of debate, since several studies have not proved its effect on clinical outcomes associated with atherosclerosis. Cardiovascular-related morbidity and mortality was assessed in a post-hoc approach four years after baseline characterization of patients (male/female n = 36/32) with angiographically proven coronary heart disease. CD14 C(-260)--> T promoter genotype was determined at baseline. Seventeen out of 20 CHD patients with non-lethal cardiovascular events carried at least one T-allele. CD14 T-260 allele carriers have a 3.59-fold (95 % confidence interval: 1.11-6.75) increased risk for non-lethal cardiovascular events (Kaplan-Meier plot: log rank test p = 0.029). All patients with lethal outcomes (n = 6) were also T-allele carriers. Multivariate logistic regression analysis among CHD patients including age, established risk factors and the C(-260)--> T polymorphism as covariates and non-lethal events as a dependent variable confirmed the independent prospective effect of the T-allele on cardiovascular outcomes in this subset. Further evidence is provided for the role of CD14 C(-260)--> T promoter polymorphism as a genetic susceptibility marker of atherosclerosis in patients with an advanced clinical course of the disease. Due to the small sample size and post-hoc character of the study large-scale prospective studies that monitor patients with proven CHD are needed to confirm these findings.

Severe Hyperkalemia Complicating Voriconazole Treatment in a Kidney Transplant Recipient With Histoplasmosis: A Case Report.

Voriconazole is an antifungal agent that is commonly used in immunocompromised patients who develop fungal infections. We report a case of severe recurrent hyperkalemia that developed after starting voriconazole for the treatment of histoplasmosis in a kidney transplant patient who was maintained on tacrolimus-based immunosuppression. Hyperkalemia developed despite reducing the tacrolimus dose to maintain levels in a low therapeutic range. Although interactions between azoles and calcineurin inhibitors are widely recognized, this is the 1st report describing new-onset hyperkalemia following initiation of voriconazole in a kidney transplant patient receiving tacrolimus.

Endocrine and behavioural plasticity in response to juvenile stress in the semi-precocial rodent Octodon degus.

The present study in the South American rodent Octodon degus shows for the first time that the postnatal development of hypothalamic-pituitary-adrenal axis function in this semi-precocial species differs from that of altricial rodents, i.e. rats or mice, in several aspects. Our experiments revealed a particular pattern of hypothalamic-pituitary-adrenal axis activity during the first 3 weeks of life characterized by (i) a period of low plasma glucocorticoid concentrations, during which (ii) brief stress exposure (1 h parental separation) is able to elevate glucocorticoids significantly. In addition, (iii) repeated stress exposure (1 h parental separation daily) during the first 3 weeks of life resulted in females, but not in males, in an attenuated separation-induced increase of glucocorticoids, and a higher behavioural activity in both sexes at postnatal day 21. These data indicate that parental separation early in life acts as a 'strong' stressor in this species, which on the long run can alter endocrine stress response at the time of weaning in a sex-specific manner. These findings support the role of the hypothalamic-pituitary-adrenal axis as one of the key factors mediating the effects of early life stress on the neuronal network and behaviour in O. degus.

Early recurrence of nephrotic syndrome (immunoglobulin m nephropathy) after renal transplantation successfully treated with combinations of plasma exchanges, immunoglobulin, and rituximab.

In contrast to focal segmental glomerulosclerosis, which is well known to recur early in a renal graft, there are only few cases described with recurrence of immunoglobulin M (IgM) nephropathy after transplantation. We herein describe a patient with early recurrence of IgM nephropathy. A 15-year-old boy with nephrotic syndrome (IgM nephropathy) proceeding to end-stage renal disease was on dialysis before living related renal transplantation. Native kidneys were not removed. Standard immunosuppression including steroids, tacrolimus, and mycophenolate mofetil yielded initially good graft function with the s-creatinine falling to 73 micromol/L. Proteinuria was present on day 1, increasing to 20 g/L after 3 days. S-creatinine increased to 158 micromol/L and urine production diminished. A graft biopsy showed no rejection or glomerulopathy but protein vacuoles were seen within tubular cells indicating massive proteinuria. Treatment with plasma exchanges, immunoglobulin, and steroids was started. Hemodialysis was necessary. Proteinuria improved to 3.5 g/L, but s-creatinine continued to rise and a second graft biopsy showed vascular rejection (Banff type IIA). The patient was treated with antithymocyte globulin and further plasma exchanges. A single dose of rituximab was given. Five months after transplantation the s-creatinine was 67 micromol/L and there was no proteinuria. In this case early recurrence of nephrotic syndrome occurred on the first posttransplant day in combination with later occurring vascular rejection. Successful treatment included a combination of plasma exchanges, rituximab, immunoglobulin, and antithymocyte globulin.

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Comparative biological responses to human Sonic, Indian, and Desert hedgehog.

A comprehensive comparison of Sonic (Shh), Indian (Ihh), and Desert (Dhh) hedgehog biological activities has not previously been undertaken. To test whether the three higher vertebrate Hh proteins have distinct biological properties, we compared recombinant forms of the N-terminal domains of human Shh, Ihh, and Dhh in a variety of cell-based and tissue explant assays in which their activities could be assessed at a range of concentrations. While we observed that the proteins were similar in their affinities for the Hh-binding proteins; Patched (Ptc) and Hedgehog-interacting protein (Hip), and were equipotent in their ability to induce Islet-1 in chick neural plate explant; there were dramatic differences in their potencies in several other assays. Most dramatic were the Hh-dependent responses of C3H10T1/2 cells, where relative potencies ranged from 80nM for Shh, to 500nM for Ihh, to >5microM for Dhh. Similar trends in potency were seen in the ability of the three Hh proteins to induce differentiation of chondrocytes in embryonic mouse limbs, and to induce the expression of nodal in the lateral plate mesoderm of early chick embryos. However, in a chick embryo digit duplication assay used to measure polarizing activity, Ihh was the least active, and Dhh was almost as potent as Shh. These findings suggest that a mechanism for fine-tuning the biological actions of Shh, Ihh, and Dhh, exists beyond the simple temporal and spatial control of their expression domains within the developing and adult organism.

Prevalences of hyperhomocysteinemia, unfavorable cholesterol profile and hypertension in European populations.

BACKGROUND: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. OBJECTIVES: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. DESIGN: Cross-sectional data on 12,541 men and 12,948 women aged 20 + y were used from nine European studies. RESULTS: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60+ years). CONCLUSIONS: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid.

Effect of added fat on plasma glucose and insulin response to ingested potato in individuals with NIDDM.

OBJECTIVE: In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM. RESEARCH DESIGN AND METHODS: Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, alpha-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline. RESULTS: The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol.h.L-1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol.h.L-1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C-peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma alpha-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected. CONCLUSIONS: In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.

Acute metabolic response to high-carbohydrate, high-starch meals compared with moderate-carbohydrate, low-starch meals in subjects with type 2 diabetes.

OBJECTIVE: The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration. RESEARCH DESIGN AND METHODS: The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700. RESULTS: The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, high-carbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets. CONCLUSIONS: A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.

Effects of dose of ingested glucose on plasma metabolite and hormone responses in type II diabetic subjects.

Ten untreated type II (non-insulin-dependent) diabetic subjects were given 15, 25, 35, and 50 g glucose orally. Plasma glucose, insulin, C-peptide, glucagon, urea nitrogen, alpha-amino acid nitrogen, and lactate concentrations were measured, and net 5-h postprandial areas were calculated. The net glucose-area response to the ingested glucose dose (with the 0-time value as a constant baseline) was best described by a second-order polynomial equation, whereas insulin-area response was best described by a third-order equation. In a separate study, 5 untreated type II diabetic subjects were given only water, and the same metabolites and hormones were measured. Data from this study indicated that the baseline was not constant during the 5 h of study but decreased progressively. The net glucose-area and insulin-area responses to ingested glucose dose (with the decreasing baseline) were then best described by third-order equations. Glucagon, alpha-amino acid nitrogen, and lactate concentrations were exquisitely sensitive to a rise in glucose and insulin concentrations. These were all decreased with the lowest concentration of glucose used. At this dose of glucose, the increase in insulin was only 15 microU/ml.

Angioplasty catheters: manufacturing and material problems addressed.

This article describes a project to determine the causes of a high failure rate in one manufacturer's percutaneous transluminal coronary angioplasty catheters. Recommendations for optimal production are outlined.

Hypercortisolism due to an autonomously functioning pituitary adenoma: limitations in diagnostic test procedures.

We report a patient with pituitary-dependent Cushing's syndrome in whom standard biochemical testing procedures failed to define the pituitary as the source of autonomous hormone secretion. Anomalous findings included: 1) wide variations of urinary steroid excretion during a 4-day dexamethasone suppression test, 2) a rise of the serum cortisol after the single dose (8 mg) overnight dexamethasone suppression test, 3) a diminished serum 11-deoxycortisol response to the metyrapone test, and 4) an absent plasma ACTH response to CRH. While the results of these studies were most consistent with an ectopic source of ACTH production, magnetic resonance imaging suggested that Cushing's syndrome was due to a pituitary adenoma. The adenoma was removed by transphenoidal surgery. However, serum and urinary steroid levels remained measurable for 2 weeks because of the perioperative use of im cortisone acetate. Subsequent im administration of 200 mg cortisone acetate again led to prolonged serum and urinary steroid responses to this compound, thus emphasizing the pitfalls that may accompany the perioperative use of cortisone acetate. This patient demonstrates the importance of performing multiple tests, including magnetic resonance image scanning, in evaluation Cushing's syndrome, since standard biochemical testing may not indicate pituitary ACTH hypersecretion as the cause.