Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1

The elimination half-life of fluoride is significantly increased in patients with chronic renal failure. This led us to conduct a study of variations of its plasma levels in 35 patients receiving dialysis treatment. In this population, there is a gaussian distribution of the values before and after the hemodialysis session, with a significant decrease in the averages. Furthermore, there is a highly significant correlation between fluoride levels before and after the dialysis session (P < 0.00001), and also between the amount of time in hemodialysis (in months) and the average fluoride level before dialysis (r = 0.624; P = 0.008). The presence of a group of patients consuming fluoride waters such as Vichy St-Yorre Water was easily identified by their excessive fluoride levels (above 100 micrograms/l), which could have a tendency to increase the risks of this group.     

A comparison of daily fluoride intakes from food samples in Japan and Brazil

The purpose of this study was to analyse the fluoride content of Japanese infant foods and foods in Brazil and to estimate daily fluoride intake calculated for a 6-month-old infant which reflects supplemental fluoride increased from infant foods and decreasing breast-feeding and commercial milk-feeding. Fluoride concentrations of 26 samples were assessed by a modified microdiffusion method and fluoride ion selective electrode. The fluoride content varied from 0.53 to 1.33 microgram/g for milk-base formulas, from 0.46 to 2.94 micrograms/g for infant foods in Japan, and from 0.06 to 0.25 microgram/g for foods in Brazil. The daily fluoride intake was calculated according to feeding pattern. The minimum and maximum fluoride values were 0.080 mg/day and 0.248 mg/day, respectively. These fluoride intakes, expressed in milligrams per kg of fluoride intake, ranged from 0.010 to 0.033 mg F/kg body weight. No significant differences in fluoride intake values were found between Japanese infant foods and foods in Brazil. The results of this study indicate that daily fluoride intakes of Japanese infant foods and foods in Brazil could be considered within the optimal recommended level.     

Fluorides in the body of the mother and in the fetus. III. Fluorides in amniotic fluid

Fluoride concentrations in amniotic fluid as well as in venous and arterial cord blood serum were determined in 20 women during the perinatal period. The mean concentrations of fluoride from amniotic fluid, venous cord blood serum and arterial cord blood serum were 1,6 +/- 0,18 mumol/l, 3,2 +/- 0,28 mumol/l and 2,9 +/- 0,39 mumol/l respectively. Amniotic fluid fluoride concentrations were significantly higher in the older age group of pregnancies (39-42 weeks) in comparison with the younger age group of pregnancies (34-38 weeks) p < 0,01. The reasons for mentioned relations were discussed.     

Fluoride therapy in prevention of rheumatoid arthritis induced bone loss

OBJECTIVE: To determine the efficacy of sodium fluoride (40 mg/day) in preventing rheumatoid arthritis (RA) induced bone loss, which may lead to osteoporosis. METHODS: We conducted an 18 month, randomized, double blind, placebo controlled trial in 38 patients with RA. The primary outcome measure was the difference in the percentage change between groups in lumbar spine bone mineral density (BMD) from baseline values after 18 months of therapy. The secondary outcome measures were the differences in the percentage change between groups in femoral neck, Ward's triangle, trochanter, and total body BMD from baseline after 18 months of therapy. RESULTS: There was a significant percentage difference (SD) between groups of 6.2% (7.3%) (p = 0.0005) in lumbar spine BMD after 18 months of treatment in favor of the fluoride group. The fluoride group experienced a 5.2% (8.4%) (p = 0.0125) increase, whereas the placebo group showed a 1.0% (4.8%) (p = 0.8015) decrease in lumbar spine BMD after treatment. No significant differences were found for the femoral neck, Ward's triangle, trochanter, and total body BMD in terms of the percentage changes from baseline within each treatment group or in the differences in the degree of change between groups after therapy. Lumbar spine BMD increased in about 80% of patients treated with fluoride (responders) compared to 44% of patients treated with placebo. CONCLUSION: The results showed that fluoride therapy was well tolerated and increased vertebral bone mass in patients with RA.     

The effects of fluoride concentration and the level of cariogenic challenge on caries development in desalivated rats

Dental caries is an infectious and transmissible disease that continues to affect the majority of people. The presence of carbohydrate, mainly sucrose in the diet, is an important factor in its occurrence. The amount of fluoride required for optimal protective effect where there is a high caries challenge is unclear. Differences in the intensity of cariogenic challenge, for whatever reason, may play a part in determining fluctuations in the effectiveness of fluoride. The purpose of this study was to evaluate the effect of different concentrations of fluoride on the development of caries and explore the cariostatic effect of fluoride under various levels of cariogenic challenge. The study comprises two experiments. In experiment I, 60 desalivated Sprague Dawley rats infected with Streptococcus sobrinus were offered the following to drink for 21 days: group (1), sterile distilled water (SDW); (2) 10 parts/10(6) F SDW; (3) 20 parts/10(6) F SDW; (4) 30 parts/10(6) F SDW; (5) 40 parts/10(6) F SDW. In experiment II, eight groups of 9 rats were placed in a K?nig H?fer programmed feeder and were exposed to different levels of cariogenic challenge through varying frequency of eating and offered water containing 10 parts/10(6) F. In experiment I, exposure to 20, 30 and 40 parts/10(6) F reduced caries development significantly: fluoride, at 10 parts/10(6), reduced the severity of the carious lesions. In this model of severe cariogenic challenge, the results suggest that elevated concentrations of fluoride might be effective in patients at high caries risk. In experiment II, fluoride reduced the incidence and severity of smooth-surface caries in all groups. The protective effect of fluoride decreased as the number of exposures to sugar increased. It is concluded that the effectiveness of fluoride is influenced by the level of cariogenic challenge and that consideration should be given to adjusting the level of fluoride exposure based on perceived caries risk, and that there is a maximum therapeutic effect of fluoride beyond which no additional protection can be expected.     

Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of Cyclofem in Chinese women

The intake of fluorides with water, food, dental fluoride preparations, or in particular fluoride supplements, such as NaF tablets, may lead to dental fluorosis. In the present study conducted in a nonfluoridated area in Germany, developmental enamel defects were examined using the Modified Developmental Defects of Enamel Index (Mod DDE Index), which subdivides enamel defects into the categories demarcated (Mod DDE score 1) and diffuse (Mod DDE score 2) opacities and hypoplasia (Mod DDE score 3). 158 children, between 8.5 and 10 years old, were assigned to three examination groups, defined by three different fluoride tablet programs. The children in all three examination groups, F1, F2, and F3, had received 0.25 mg F-/day up to the age of 2 years, F1 and F3 from birth on, F2 beginning with the 7th month of life. F1 and F2 received 0.5 mg F-/day during the 3rd and 0.75 mg F-/day during the 4th and 5th year of life. For F3, beginning with the 3rd year of life, no further recommendations were made. 158 sociodemographically matched children living in a neighboring town served as controls and did not take part in any structured fluoride supplementation program. The proportions of children with Mod DDE scores 1, 2, or 3 at least in one index tooth were significantly higher in the examination groups (40%) than in the control group (20%). Also, the proportions of children with Mod DDE score 2 at least in one index tooth were significantly higher in the examination groups (18%) than in the control group (8%). The proportions of children with Mod DDE score 1 at least in one index tooth were 25% in the examination groups and 17% in the control group. No Mod DDE score 3 was found. Not more than 5% of the children in each group had 50% of their teeth with Mod DDE score 1, 2, or 3. The proportions of teeth per child with Mod DDE score 2 were significantly higher in the examination group than in the control group. While uncontrolled variables cannot be excluded, the observed differences between the experimental and control groups may be attributed to the ingestion of fluoride tablets in the experimental group.     

Fluoride toxicity: a biochemical and scanning electron microscopic study of enamel surface of rabbit teeth

The present study has been carried out to investigate the effect of fluoride toxicity on the morphology as well as inorganic chemical constituents of rabbit teeth. Rabbits were administered sodium fluoride at a dose of 10 mg NaF/kg body weight every 24 h for 18 and 23 months. The incisor and molar teeth (whole tooth) were investigated for fluoride, calcium and phosphorus content in 18- and 23-month treated animals. The enamel surfaces of incisor teeth of 23-month treated animals were examined under scanning electron microscope. A significant increase in fluoride levels and significant decrease in calcium content was found following fluoride administration for 18 and 23 months as compared to control. Ca/P ratio was significantly increased only in 23-month treated animals. The scanning electron micrographs revealed hypoplastic, rough, uneven, pitted and cracked enamel surfaces covered with granular deposits as a result of excessive intake of fluoride. It can be concluded that long term fluoride administration leads to severe structural alterations on the enamel surface, possibly through defective mineralization.     

Pulmonary rehabilitation and self-care after ambulatory surgery

OBJECTIVES: To identify risk factors for dental fluorosis that cannot be explained by drinking water fluoride concentration alone. METHODS: Two hundred eighty-four Tanzanian children ages 9 to 19 (mean 14.0+/-SD 1.69), who were lifetime residents at differing altitudes (Chanika, 100 m; Rundugai, 840 m; and Kibosho, 1,463 m; Sites 1, 2, and 3 respectively) were examined for dental fluorosis and caries. They were interviewed about their food habits, environmental characteristics and use of a fluoride-containing food tenderizer known locally as magadi. Meal, urine, water and magadi samples supplied by the participants were analyzed for fluoride content. Urine samples were also analyzed for creatinine concentration. Four magadi samples from Sites 1 and 3 were analyzed for complete element composition. RESULTS: Of the 13 water samples from Site 2, 10 contained > or =4 mg/L F, ranging from 1.26 to 12.36 mg/L with a mean+/-SD of 5.72+/-4.71 mg/L. Sites 1 and 3 had negligible water fluoride of 0.05+/-0.05 and 0.18+/-0.32 mg/L respectively. Mean TFI fluorosis scores (range 0-9) for Site 2 were high: 4.44+/-1.68. In Sites 1 and 3, which both had negligible water fluoride, fluorosis scores varied dramatically: Site 1 mean maximum TFI was 0.01+/-0.07 and Site 3 TFI was 4.39+/-1.52. Mean DMFS was 1.39+/-2.45, 0.15+/-0.73 and 0.19+/-0.61 at Sites 1, 2, and 3, respectively. There were no restorations present. Urinary fluoride values were 0.52+/-0.70, 4.34+/-7.62, and 1.43+/-1.80 mg/L F at Sites 1, 2, and 3, respectively. Mean urinary fluoride values at Site 3 were within the normal urinary fluoride reference value range in spite of pervasive severe pitting fluorosis. Meal and magadi analyses revealed widely varied fluoride concentrations. Concentrations ranged from 0.01 to 22.04 mg/L F for meals and from 189 to 83211 mg/L F for magadi. Complete element analysis revealed the presence of aluminum, iron, magnesium, manganese, strontium and titanium in four magadi samples. There were much higher concentrations of these elements in samples from Site 3, which was at the highest altitude and had severe enamel disturbances in spite of negligible water fluoride concentration. An analysis of covariance model supported the research hypothesis that the three communities differed significantly in mean fluorosis scores (P<0.0001). Controlling for urinary fluoride concentration and urinary fluoride:urinary creatinine ratio, location appeared to significantly affect fluorosis severity. Urinary fluoride:urinary creatinine ratio had a stronger correlation than urinary fluoride concentration with mean TFI fluorosis scores (r=0.43 vs r= 0.25). CONCLUSIONS: The severity of enamel disturbances at Site 3 (1463 m) was not consistent with the low fluoride concentration in drinking water, and was more severe than would be expected from the subjects' normal urinary fluoride values. Location, fluoride in magadi, other elements found in magadi, and malnutrition are variables which may be contributing to the severity of dental enamel disturbances occurring in Site 3. Altitude was a variable which differentiated the locations.     

Determination of fluoride in bovine urine

Fluoride concentration in bovine urine is determined by using a selective ion electrode. Urine is buffered and measured against known fluoride (F) standards. The method is applicable to 2 to 40 mg F/L without further dilution. Typical normal urine contains less than 10 mg F/L. Concentrations greater than 10 mg/L support a clinical diagnosis of fluorosis in cattle. Repeatability coefficient of variation (CV) ranged from 1.6 to 3.5% for F concentrations of 3.2-43 mg/L. Reproducibility CV ranged from 0.3 to 7.3% for F concentrations of 7.0-17.2 mg/L.     

Lack of significant effect of coffee and caffeine on fluoride metabolism in rats

It has been reported that rat plasma fluoride (F) concentrations are higher by up to 100% when F is administered ig in coffee or a caffeine solution compared with when it is administered in water. It was hypothesized that the consumption of caffeinated beverages has contributed to the prevalence of dental fluorosis. The present studies were done to determine the physiological mechanisms for these effects. For approximately 2 h after F was administered in coffee, plasma F concentrations were higher than when administered in water, decaffeinated coffee, or a caffeine solution (3 mg/kg), but the intergroup differences were small and generally not statistically significant. The 4-hour plasma AUC values did not differ with statistical significance. There were no differences among the groups in the renal or extrarenal (skeletal) clearances of F, which suggested that the higher plasma F concentrations in the coffee groups may have been due to a slight and transient increase in absorption rate. The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given. In addition, the renal excretion, clearance, and fractional renal clearance of calcium did not differ among the groups. The results indicated that decaffeinated coffee and caffeine had no effect on F metabolism, whereas caffeinated coffee appeared to increase the initial absorption rate but not the 4-hour bio-availability.(ABSTRACT TRUNCATED AT 250 WORDS)     

The motor organization of the sense of rhythm

Serum inorganic fluoride levels in obese versus control patients were compared during and after sevoflurane anesthesia. Mean serum inorganic fluoride levels in the obese group increased more rapidly and were significantly higher than in the control group at each sampling time (P < 0.01). The area under the curve of fluoride concentration, versus time up to 24 h and 48 h in the obese patients, was significantly greater than that in the nonobese patients (P < 0.001). Peak serum fluoride level in the obese patients was 51.7 +/- 2.5 mumol/L and exceeded 50 mumol/L for nearly 2 h. Our study showed that serum fluoride concentrations between mildly obese and nonobese patients differed during and after sevoflurane anesthesia.     

Electrophysiological brainstem investigations in obstructive sleep apnoea syndrome

In children with steroid-resistant nephrotic syndrome (SRNS) hyperlipidaemia may in the long term be associated with progressive renal insufficiency and increased risk of coronary heart disease. We have assessed the efficacy and tolerability of diet prior to and in combination with a hydroxymethylglutaryl CoA reductase inhibitor, simvastatin, in seven children with SRNS with a mean age of 8 years (range 1.8-16.3 years). Dietary advice to maintain adequate energy and protein intakes with reduced saturated fat and cholesterol intake had little impact on lipid levels pre treatment (mean reduction in cholesterol 1 mmol/l, triglyceride 1.1 mmol/l) but was maintained throughout the study duration. The mean cholesterol and triglyceride concentrations pre treatment were 12.1 +/- 2 (SEM) mmol/l and 8 +/- 2.1 (SEM) mmol/l, respectively. On a median simvastatin dose of 10 mg/day (range 5-40 mg) there was a 41% reduction in cholesterol to 6.6 +/- 0.77 (SEM) mmol/l and a 44% reduction in triglyceride to 3.9 +/- 1.38 (SEM) mmol/l at 6 months which was sustained at 12 months in five patients. The drug was well tolerated with no clinical side effects being noted. Over 6 months the mean plasma albumin concentrations increased from 18.2 +/- 1.26 (SEM) g/l to 23 +/- 2.51 (SEM) g/l, accounted for by three patients (1 complete remission, 1 partial remission, 1 end-stage renal failure). Plasma creatinine concentrations remained stable in five patients with two having progressive chronic renal failure. Growth parameters for both weight and height were maintained. Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated.     

Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth

We evaluated the safety of ciprofloxacin administered in a dose of 15-25 mg/kg for 9-16 days, in a case series of 58 children who were between 8 months and 13 years of age. No arthropathy was observed during therapy and follow-up. Blinded evaluation of 22 pairs of nuclear magnetic resonance scans obtained before and between day 10 and 15 of therapy did not reveal any cartilage damage. After the first dose of ciprofloxacin (10 mg/kg), serum fluoride levels increased at 12 h in 15 of 19 (79%) patients; 24-h urinary fluoride excretion was higher on day 7 compared with basal values in 16 of 18 (88.9%) patients. Height z scores of 53 patients at a mean of 22.5 months of follow-up were not significantly different from basal scores (p = 0.12). In conclusion, ciprofloxacin may be recommended for use in children for short duration when effective alternative antibacterials are unavailable. However, there is a need for further studies to evaluate the tissue accumulation of fluoride and its potential to cause toxic effects.     

Pharmacokinetics of fluorine contained in the Royale Saint-Yorre mineral water

The pharmacokinetics of oral fluoride supplied by one half liter of Royale Saint-Yorre water, which contains 8.50 mg fluoride per liter, were studied in ten healthy volunteers. Fluoride plasma kinetics and urinary excretion of fluoride were determined over 24 hours. After ingestion of one half liter Royale Saint Yorre mineral water, mean peak serum fluoride level was 159 +/- 22 micrograms/l. Time to peak serum level was 1 h (0.9 +/- 0.21 h) and area under the curve from 0 to 24 hours was 1,040 +/- 168 micrograms/l/h. Mean urinary fluoride was 2.57 +/- 0.4 mg (range 1.90 to 3.32 micrograms). The authors compared their findings with previously published data on fluoride pharmacokinetics after oral administration of an enteric-coated sodium fluoride tablet containing 11.35 mg elemental fluoride (12 healthy volunteers). Both peak serum level standardized for the dose of elemental fluoride and time to peak serum level were greater with the water than with the tablet. The authors cannot conclude as to which of the two types of fluoride exhibits the best bioavailability because their absorption coefficients have not been determined. This study demonstrates that Royale Saint Yorre mineral water is a valuable source of fluoride. Additional prospective studies are needed to determine whether it has therapeutic potential.     

Fluoride concentration in the approximal area after using toothpicks and other fluoride-containing products

The aim of this work was to study the fluoride (F) concentration in the approximal area after using toothpicks and other F-containing products. The exposure time was standardised to 2 min. 24 subjects participated, divided into 4 groups, with 6 individuals per group. In 3 of the groups, the following 4 products were compared: (1) a toothpick impregnated in 4% NaF; (2) a dentifrice containing 0.32% NaF; (3) a mouthrinse solution containing 0.025% NaF; (4) a tablet containing 0.55 mg NaF. In the 4th group, 3 commercial F toothpicks and 2 F dental flosses were compared. In all 4 groups, the F concentration was determined up to 60 min at 4 approximal sites. On each sampling occasion, 3 triangle-shaped paper points were used, absorbing 3 x 1 microl. In general, the toothpick gave similar or somewhat higher F concentrations in the approximal area than the dentifrice, mouthrinse solution and tablet. Comparing the various commercial toothpicks and dental flosses, 2 of the toothpicks gave higher approximal F concentrations than the other 3 products. When comparing the series in which the very first sample was collected from 2-20 min after the F treatment, it was found that the sampling procedure itself reduced the subsequent approximal F concentration. The main conclusion from this study is that an F-impregnated toothpick is a promising vehicle for delivery of fluoride to the approximal area.     

Bioavailability and pharmacokinetic characteristics of two monofluorophosphate preparations with calcium supplement

Two studies on the rate and extent of bioavailability of fluoride from a single dose of oral preparations of sodium monofluorophosphate (Na2FPO3) combined with calcium supplement were conducted according to a cross-over design on 18 (Study 1) and 20 (Study 2) male healthy volunteers, respectively. Evaluated were: a) tablets containing 76 mg Na2FPO3 (Ref1); b) chewable tablets containing 76 mg Na2FPO3 and 1250 mg calcium carbonate (Test 1); c) effervescent tablets containing 76 mg Na2FPO and 3240 mg calcium lactogluconate/carbonate (Ref 2); d) effervescent tablets containing 76 mg Na2FPO3 and 1250 mg calcium carbonate (Test 2). In all preparations Na2FPO3 was equivalent to 10 mg elemental F. The calcium supplement was equivalent to 500 mg elemental Ca. Fluoride was assayed in serum and in urine by a gas chromatographic method with a limit of quantitation of 10 ng/ml. Test 1 was found equivalent to Ref1 with regard to rate and extent of bioavailability of fluoride in serum. Test 2 (effervescent tablets resulting in an oral solution of Na2FPO3 and calcium salts) was found bioequivalent in rate and extent to Ref2 (effervescent tablets authorized for marketing with the same content in F and Ca equivalents as Test 2). The pharmacokinetics of fluoride from all investigated preparations was characterized by a short lag time, a rapid absorption, a Cmax of fluoride of 291-351 ng/ml (without significant differences between preparations) reached 30-75 min after administration, and a terminal t1/2 of 6-14 h. About 50% of the absorbed fluoride was eliminated with the urine (from 0 to infinity time). The kur.el was 0.06 h-1. The renal clearance 65 ml/min. The preparations were well tolerated by the subjects. In conclusion, Test1 and Test2 represent combinations of Na2FPO3 with calcium supplement which are well tolerated and provide a rapid, reliable and practically complete bioavailability of fluoride. They are therefore suitable for the bone-forming therapy of osteoporosis.     

Long-term exposure to retinoic acid induces the expression of IRK1 channels in HERG channel-endowed neuroblastoma cells

T-cell types are important in maintaining immune homeostasis in the lung and their imbalance may be associated with several diseases. We examined the relationship between bronchoalveolar lavage (BAL) T-cell subset profiles and the clinical course of 46 patients with idiopathic pulmonary fibrosis (IPF). A flow cytometry cell sorter (FACS) was used to analyse the T-cell subsets. Pulmonary function tests (PFT) were performed at baseline and 6-12 months later. Patients were divided into two groups according to their CD4/CD8 ratio: CD4/CD8 >1 (group 1, n=21); and CD4/CD8 <1 (group 2, n=25). A lower percentage of lymphocytes, a higher percentage of CD8/S6F1 cells (cytotoxic T-lymphocytes) and a higher percentage of neutrophils were found in the BAL in group 2 compared to group 1 (11+/-7.5% versus 19+/-13.2%; p=0.024 and 29.8+/-17.6% versus 13.3+/-6.9%; p=0.068, respectively for lymphocytes and cytotoxic T-lymphocytes; and 8+/-11% versus 29+/-27%; p=0.003 for neutrophils). Inversely, in the peripheral blood, the distribution of CD8/S6F1 cells was lower in group 1 than in group 2 (8.3+/-6.9% versus 33.4+/-16.5%; p=0.0048). The patients were followed over a period of 1 yr in order to test whether those findings could determine efficacy of therapy. The baseline transfer factor of the lung for carbon monoxide (TL,CO) capacity in group 1 and group 2 was 59+/-22% and 51+/-21%, respectively (p=0.29), but only in group 1 was the TL,CO capacity improved significantly in response to steroids treatment after 6-12 months. IPF patients with a higher percentage of lymphocytes, a lower percentage of neutrophils, CD4/CD8 >1 and a low percentage of CD8/S6F1 may have a more benign course of disease. These parameters may identify an early stage of reversible disease responsive to therapy. We conclude that these measurements may be a useful tool in monitoring response to treatment in patients with idiopathic pulmonary fibrosis.     

Haloperidol serum concentrations and D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate

The aim of this study was to examine the relationship between serum concentrations of haloperidol and central D2 receptor occupancy in eight schizophrenic patients treated with low doses of haloperidol decanoate. The accompanying psychopathology was assessed. During a 4-week interval after administration of haloperidol decanoate (dose range 30-70 mg), serum concentrations of haloperidol were determined once a week by using a sensitive high-performance liquid chromatography method. The patients' D2 receptor occupancy was determined with single-photon emission computed tomography on two separate occasions. One week after depot administration the mean haloperidol serum concentration was 7.3 nmol/l (range 3.9-22.7 nmol/l) and the mean D2 receptor occupancy was 75% (range 52-100%). After 4 weeks the mean haloperidol serum concentration had decreased to 1.8 nmol/l (range 0-5.7 nmol/l) and the mean D2 receptor occupancy to 53% (range 12-89%). Differences were seen in two subgroups, defined by their history of neuroleptic exposure before inclusion into the study. Patients treated with depots of haloperidol decanoate for months showed higher D2 receptor occupancy and corresponding higher serum haloperidol concentrations at week 4 than did patients who had a history of oral haloperidol treatment. Because the difference in the dynamics of D2 receptor occupancy could be reflected by corresponding serum concentrations of haloperidol, it seems useful to involve haloperidol drug monitoring as a possible surrogate marker for D2 receptor occupancy in optimizing low-dose treatment with haloperidol decanoate.     

Human submandibular saliva specifically inhibits HIV type 1

This study was performed to investigate the possible association between preeclampsia and the plasma concentrations of Lp(a) lipoprotein and TGF-beta1 in a large series of patients. Additionally, correlation between the concentrations of these molecules and the severity of preeclampsia or fetal growth retardation was evaluated. Following clinical examination and biochemical analyses, both electroimmunoassay and RIA technique were used for quantitative determinations of plasma Lp(a) lipoprotein. ELISA technique was used to measure the active form of TGF-beta1 in plasma of pregnant normotensive and preeclamptic women. We examined 154 women with preeclampsia (preeclampsia group) and 76 healthy, pregnant normotensive women (control group). The preeclampsia group was further divided into the following subgroups: mild preeclampsia, severe preeclampsia and preeclampsia with fetal growth retardation. Plasma levels of Lp(a) lipoprotein were lower in the total preeclampsia group as well as in all preeclampsia subgroups (5.45+/-7.41, 5.58+/-8.02, 5.08+/-5.38, and 4.32+/-5.28 mg/dl in the total preeclampsia group, and in subgroups with mild preeclampsia, severe preeclampsia, and preeclampsia with fetal growth retardation, respectively) than in the control group (7.84+/-9.26 mg/dl) as determined by quantitative electroimmunoassay. Corresponding results were obtained with a radioimmunoassay (166.03+/-200.2 U/l in the total preeclampsia group vs. 229.18+/-257.7 U/l in controls). There was good correlation between the two methods used for Lp(a) lipoprotein measurement. The differences between controls and the total preeclampsia group as well as each preeclampsia subgroup were statistically significant by a non-parametric test (one-way Kruskal-Wallis test). Plasma concentrations of the active form of TGF-beta1 were increased in all preeclampsia subgroups as well as in the total group (5.63+/-1.68 ng/ml) compared to controls (4.67+/-1.33 ng/ml). This increase in TGF-beta1 was statistically highly significant. Plasma concentrations of Lp(a) lipoprotein and the active form of TGF-beta1 did not differ significantly between the preeclampsia subgroups. The outcome of this study may suggest involvement of both parameters in the pathophysiology of preeclampsia and may substantiate the notion of a multifactorial etiology of the disease.     

Transdermal estrogen replacement therapy: beneficial effects on hemostatic risk factors for cardiovascular disease

OBJECTIVES: To assess the effect of estrogen replacement therapy on hemostatic risk factors for cardiovascular disease (CVD) in postmenopausal women during 2 years of treatment. METHODS: In an open prospective study, patients (n = 42) were investigated before and during 2 years of treatment, and compared to an untreated postmenopausal control group (n = 18) followed during the same period, healthy premenopausal women (n = 20) being included as a reference group for premenopausal values. The patients underwent treatment with transdermal 17 beta-estradiol (E2) (50 micrograms/24 h), oral medroxyprogesterone acetate (5 mg/day) being added for 12 days every second month. RESULTS: After 2 years of treatment there was a significant increase in t-PA antigen (P = 0.01) and a significant decrease in F VII antigen (P = 0.01). PAI-1 antigen concentrations decreased slightly. Fibrinogen concentrations were already significantly decreased at 3-month follow-up (P = 0.01), and were still low after 2 years. By contrast, at 2-year follow-up the postmenopausal control group manifested significant increases in F VII and PAI-1 antigen and slight increases in fibrinogen, which resulted in significant differences between patients and controls. Regression analysis showed the increase in the serum estradiol concentrations to be inversely correlated to the decreases in the plasma concentrations of F VII antigen (r = -0.34, P = 0.001) and fibrinogen (r = -0.35, P = 0.001). There were no changes in AT III or protein C in any group. CONCLUSIONS: The increase in serum estradiol concentrations due to replacement therapy did not adversely affect the studied components of the fibrinolytic and protein C defense system against thrombosis, and resulted in beneficial decreases in F VII antigen and fibrinogen. These findings may help to explain the beneficial effects of estrogen replacement therapy in terms of protection from cardiovascular disease.