High‐throughput quantification of selenium in individual serum proteins from a healthy human population using HPLC on‐line with isotope dilution inductively coupled plasma‐MS

In this study, a method, based on dual column affinity chromatography hyphenated to isotope dilution inductively coupled plasma–quadrupole MS, was developed for selenium determination in selenoprotein P, glutathione peroxidase, and selenoalbumin in human serum samples from a group of healthy volunteers (n=399). Method improvement was achieved using methanol‐enhanced isotope dilution which resulted in improved sensitivity and removal of isobaric interferences. Although no human serum reference materials are currently certified for their selenium species levels, method development was conducted using human serum reference material BCR 637 and 639 as their Se species content has been reported in the previous studies, and thus comparisons were possible. The mean selenium concentrations determined for the 399 healthy volunteer serum samples were 23±10 ng Se mL^?1 for glutathione peroxidase, 49±15 ng Se mL^?1 for selenoprotein P and 11±4 ng Se mL^?1 for selenoalbumin. These values are found to be in close agreement with published values for a limited number of healthy volunteer samples, and to establish baseline Se levels in serum proteins for an apparently healthy group of individuals, thus allowing for subsequent comparisons with respective values determined for groups of individuals with selenium related health issues, as well as assist in the discovery of potential selenium biomarkers. Also, the relationship between Se serum protein levels and some anthropometric characteristics of the volunteer population were investigated. Additionally, further development of the analytical method used in this study was achieved by adding a size exclusion chromatography column after the two affinity columns via a switching valve. This allowed for the separation of small selenium‐containing molecules from glutathione peroxidase and thus enhanced the overall confidence in its identification.     

Establishment of Radioimmunoassay for Human Macrophage Colony-stimulating Factor Using Recombinant Human Macrophage Colony-stimulating Factor as Tracer and Immunogen

A sensitive and reliable radioimmunoassay (RIA) for human macrophage colony-stimulating factor (M-CSF) was developed using recombinant human M-CSF (rhM-CSF) as tracer and immunogen. The assay was quantitative over the range of 50 pg/ml and 5.0 ng/ml for M-CSF in human urine and serum, and more sensitive and specific than the murine bone marrow assay. The average level of human M-CSF in urine from normal males (N = 71) and females (N = 46) was 3.94 ± 1.78 ng/ml (2.85 ± 1.15 μg/g creatinine), and 3.53 ± 1.70ng/ml (3.31 ± 1.12 μg/g creatinine), respectively. The serum levels were 1.95 ± 0.38ng/ml for males (N = 117), and 1.93 ± 0.49 ng/ml for females, (N = 16). The results with the urine and sera showed that there was no difference in the M-CSF levels due to age or gender.     

Timing of Bifidobacterium Administration Influences the Development of Allergy to Ovalbumin in Mice

C3H/HeJ mice were sensitized with ovalbumin (OVA) and choleratoxin (CT) for 5 weeks, and then Bifidobacterium bifidum BGN4 was administered continuously for 7 weeks, starting 2 weeks before (pre-treatment group) and 2 weeks after (post-treatment group) the initial sensitization. After sensitization, the OVA-induced (sham group) mice showed growth inhibition and had scab-covered tails which was associated with serum levels of 9887±175 ng OVA-specific IgE/ml and 758±525 ng IgG1/ml. The sera of the pre-treatment group had 4805±245 ng OVA-specific IgE/ml and 193±87 ng IgG1/ml, as well as less severe tail symptoms. The sera of the post-treatment group had 5723±207 ng OVA-specific IgE/ml but the IgG1 and IgG2a levels were the same as those of the sham group. In spleen cultures, both pre-treatment and post-treatment increased the levels of IFN-γ but decreased the levels of IL-6 and IL-18. Taken together, the in vivo and in vitro results show that treatment with Bifidobacterium before OVA sensitization suppresses or modulates the allergic response more effectively than treatment with Bifidobacterium following OVA sensitization.     

Serum levels of testosterone and gonadotrophins with respect to smoking status and genetic polymorphism of <Emphasis Type="Italic">GSTT1</Emphasis>

Objectives It is reported that parental exposure to toxicants can influence offspring sex ratio at birth. Studies have reported that several chemicals found in cigarette smoke are substrates of glutathione S-transferase T1 (GSTT1, a member of GSTθ). To determine the effect of cigarette smoke on serum levels of testosterone and gonadotrophins of smokers and possible association of these hormones levels with GSTT1 polymorphism, the present study was done. Methods Our study was conducted on 181 (40 smokers, 141 non-smokers) male subjects. Genomic DNA was extracted from peripheral blood. The GSTT1 genotyping was performed using PCR-based method. All measurements for testosterone, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were done in one laboratory. Results In smoker subjects the mean ± sd of serum testosterone, FSH, and LH were 4.64 ± 1.63 ng/ml, 2.72 ± 1.17 IU/l, and 3.03 ± 1.04 IU/l, respectively. In non-smoker subjects the mean ± sd of serum testosterone, FSH, and LH were 4.49 ± 1.24 ng/ml, 2.89 ± 1.26 IU/l, and 3.07 ± 1.28 IU/l, respectively. There was no significant difference between smokers and non-smokers for serum testosterone (t = 0.622, df = 179, P = 0.535), FSH (t = −0.757, df = 179, P = 0.450), and LH (t = −0.179, df = 179, P = 0.858). Also there was no significant difference between smokers and non-smokers in either GSTT1 null or positive genotypes for levels of testosterone, FSH, and LH. Conclusion Based on present data, it might be concluded that serum levels of testosterone and gonadotrophins were not significantly different between smoker and non-smoker males in both null and present GSTT1 genotypes.     

Vanadium levels in urine and cystine levels in fingernails and hair of exposed and normal persons

Vanadium was determined by radiochemical neutron activation analysis (RNAA) with proven accuracy in urine of workers occupationally exposed to vanadium-rich dust in a vanadium pentoxide production plant, and values in the range of 3.02–762 ng/mL (median 33.0 ng/mL) were found. In a control group consisting of administrative workers of the plant, urinary vanadium levels were found in the range of 1.05–53.4 ng/mL (median 2.53 ng/mL), whereas in an another control group of occupationally nonexposed persons, these values amounted to 0.066–0.489 ng/mL (median 0.212 ng/mL). Accuracy of the results was tested by analysis of reference material IAEA A-13 Animal Blood and NIST SRM-1515 Apple Leaves, and very good agreement was found with literature and the NIST certified values, respectively. Unlike urine, no significant differences were found for cystine levels in fingernails and hair of exposed and control persons.     

Impact du thé vert “Camellia sinensis” sur les effets du vanadium sur la croissance et l’appareil génital du ratWistar mâle

Some heavy metals are known to exert harmful effects by generating an oxidative stress which, in turn, can affect the sexual and reproductive functions of male animals. The addition of antioxidants to the diet could decrease the cytotoxic effect related to oxidative stress (in the presence of heavy metals as food or water contaminants). As a contribution to this problem, the protective effect ofCamellia sinensis green tea, which is know to be rich in antioxidant compounds (polyphenols, etc.), was studied in vanadium-treated adult male rats, with particular attention to growth and genital tract function. White male Wistar rats were given ammonium metavanadate in drinking water (0.46 g/L) for 90 days One group of animals received green tea supplement in drinking water and the control group did not. Chronic vanadium intoxication (without green tea supplement) induced a low growth rate and relative atrophy of the testes, epididymis, prostate and seminal vesicles. Motility and number of spermatozoa were also decreased. Histological examination of the testes revealed atrophy of the seminiferous tubules and defects of spermatogenesis leading to the absence of spermatozoa in 50% of seminiferous tubules. Blood testosterone levels, evaluated by radioimmunoassay, were also decreased from day 2 to day 20. In control animals, these levels were 0.717±0.107 ng/ml; 4.366±0.666 ng/ml and 1.979±0.42 ng/ml on day 2, day 10 and day 20, respectively. After vanadium treatment, they were reduced to 0.043±0.012 ng/ml, 2.494±0.17 ng/ml and 1.086±0.53 ng/ml, respectively, at the same periods. These morphological, histological and functional disorders mostly occured during the first phase of the intoxication period (day 2 to day 10) and were subsequently attenuated, indicating adaptation to the poisoning. In rats receiving green tea, vanadium ingestion did not modify growth rate compared to control animals. Very minor changes were observed in the genital tract. Testicular atrophy and absence of spermatozoa were observed in only some seminiferous tubules. Our results underscore the protective effect of green tea on vanadium poisoning. Polyphenols, which are abundant in green tea, are known to chelate iron. It is proposed that polyphenols may also form insoluble complexes with vanadium, allowing it to be eliminated in the feces. This could explain the decreased effects of vanadium poisoning under our experimental conditions.     

Seasonal changes in serum dehydroepiandrosterone,androstenedione, and testosterone levels in the squirrel monkey (Saimiri boliviensis boliviensis)

The squirrel monkey (Saimiri boliviensis boliviensis) has a well-defined breeding season during which adult males undergo androgen-dependent morphological changes, with acquisition of active spermatogenesis. To assess the hormonal events of this annual cycle, blood samples were obtained weekly from ten adult males, and serum was assayed for testosterone (T), androstenedione (ΔA), and dehydroepiandrosterone (DHEA). A significant seasonal variation was noted in mean serum T (P < 0.02), ΔA (P < 0.02), and DHEA (P < 0.001) concentrations. Mean ΔA concentrations increased from a nonbreeding season nadir of 91.4 ± 12.9 ng/ml (mean ± standard error) to a prebreeding concentration of 139 ± 10.5 ng/ml and breeding season peak of 167.5 ± 15.4 ng/ml (P < 0.05). Mean DHEA concentrations increased from a nonbreeding season nadir of 8.3 ± 0.8 to a breeding season peak of 14.3 ± 1.2 (P < 0.001). Mean T levels in the nonbreeding (52.2 ± 11.6 ng/ ml) and prebreeding season (48.6 ± 7.4) were similar. However, T significantly increased during the breeding season to 103.5 ± 12.8 ng/ml (P < 0.05). Progressive changes in body weight and morphology paralleled the rise in serum ΔA levels. The pattern of peripheral serum androgen concentrations throughout the year would suggest annual activation of the hypothalamic-pituitary-adrenal and/or hypothalamic-pituitary-gonadal axes.     

Essential trace elements in humans

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n=85) and of healthy controls (n=25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5±1.8 ng/mL vs 10.6±1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.     

Growth hormone and ghrelin secretion in severely obese women before and after bariatric surgery

Objective: The objective was to evaluate ghrelin and growth hormone (GH) interactions and responses to a growth hormone‐releasing hormone (GHRH)/arginine test in severe obesity before and after surgically‐induced weight loss. Research Methods and Procedures: Our study population included 11 severely obese women 39 ± 12 years of age, with a mean BMI of 48.6 ± 2.4 kg/m², re‐studied in a phase of stabilized body weight, with a BMI of 33.4 ± 1.2 kg/m², 18 months after having successfully undergone biliopancreatic diversion (BPD). A GHRH/arginine test was performed before and 18 months after BPD to evaluate ghrelin and GH interactions. Active ghrelin, measured by radioimmunoassay (RIA), and GH, measured by chemiluminescence assay, were assayed before and after the GHRH/arginine test. Results: Fasting serum GH levels and GH area under the curve (AUC) significantly increased from 0.2 ± 0.05 ng/mL to 1 ± 0.3 ng/mL (p < 0.05) and from 514.76 ± 98.7 ng/mL for 120 minutes to 1957.3 ± 665.1 ng/mL for 120 minutes after bariatric surgery (p < 0.05), respectively. Although no significant change in fasting ghrelin levels was observed (573 ± 77.9 before BPD vs. 574.1 ± 32.7 after BPD), ghrelin AUC significantly increased from ?3253.9 ± 2180.9 pg/mL for 120 minutes to 1142.3 ± 916.4 pg/mL for 120 minutes after BPD (p < 0.05). Fasting serum insulin‐like growth factor (IGF)‐1 concentration did not change significantly (133.6 ± 9.9 ng/mL before vs. 153.3 ± 25.2 ng/mL after BPD). Discussion: Our study demonstrates that the mechanisms involved in ghrelin and GH secretion after the secretagogue stimulus (GHRH/arginine) are consistent with patterns observed in other populations.     

Factors affecting the levels reported for vanadium in human serum

Chemometric techniques may be applied to extract significant analytical information from a series of publications that present methods and results for determining trace elements in biological material. This approach was applied to the total of 28 papers published in 1971–1988 that reported determination of vanadium in normal human serum or plasma; the levels spanned four orders of magnitude. The most important factors affecting the analytical results were found to be the choice of analytical method and the experience of the laboratory in trace-element research. Results from the most experienced laboratories with the best analytical methods were found to be correlated with the precision of the data, indicating that the correct concentration of vanadium would be<1 mg/m³. This is in agreement with results subsequently obtained by radiochemical neutron activation analysis of eight samples of serum from Danish colleagues.     

Determination of subnanomolar concentrations of vanadium in environmental water samples using flow injection with luminol chemiluminescence detection

A flow injection chemiluminescence method is described for the determination of subnanomolar concentrations of vanadium in environmental water samples. The procedure is based on the oxidation of luminol in the presence of dissolved oxygen catalyzed by vanadium(IV). Vanadium(V) reduction and preconcentration of vanadium(IV) was carried out using in‐line silver reductor and 8‐hydroxyquinoline chelating columns at pH 3.15, respectively. The calibration graph for vanadium(IV) was linear in the concentration range of 0.025–10 µg/L with relative standard deviation in the range of 0.4–5.58%. The detection limit (3s blank) was 3.8 × 10^?3 µg/L without preconcentration; when the vanadium(IV) was preconcentrated with an 8‐HQ column for 1 min (2.0 mL of sample loaded), the detection limit of 5.1 × 10^?4 µg/L was achieved. One analytical cycle can be completed in 2.0 min. The analysis of certified reference materials (CASS‐4, NASS‐5 and SLRS‐4) by the proposed method showed good agreement with the certified values. The method was successfully applied to the determination of total dissolved vanadium in environmental water samples. Copyright © 2010 John Wiley & Sons, Ltd.     

Identification and Distribution of m- and p-Hydroxyphenylacetic Acids in the Brain of the Rat

The m and p isomers of hydroxyphenylacetic acid have been identified and quantitated in whole rat brain and in several regions using a capillary column high resolution gas chromatography–mass spectrometry procedure. Their concentrations were: for m-hydroxyphenylacetic acid (mean ± S.E., number of determinations in parentheses)—whole brain, 2.3 ± 0.3 ng/g (7); hypothalamus, 1.2 ± 0.3 ng/g (5); caudate nucleus, 5.5 ± 0.6 ng/g (5); brain stem, 1.8 ± 0.1 ngig (5); cerebellum, 1.2 ± 0.1 ng/g (5) and the “rest,” 1.7 ± 0.1 ng/g (5); and for p-hydroxyphenylacetic acid–whole brain, 10.6 ± 0.7 ng/g (7); hypothalamus, 4.5 ± 0.1 ng/g (4); caudate nucleus, 28.3 ±1.6 ng/g (5); brain stem, 8.6 ± 0.6 ng/g (5); cerebellum, 8.1 ± 0.4 ng/g (9, and the “rest,” 5.3 ± 0.5 ng/g (5). This heterogeneous distribution parallels closely that exhibited by their respective precursor amines, m- and p-tyramine.     

Diurnal variations of androgens in sexually mature male Bolivian squirrel monkeys (Saimiri sciureus) during the breeding season

To assess diurnal fluctuations of serum androgens and cortisol in adult male Bolivian squirrel monkeys, these steroids were measured at predetermined times (0300, 0900, and 2300 hours) during two separate 24-hour periods in the breeding season (January 1983 and late November 1983). A significant diurnal change in serum cortisol was noted, with a nadir of 99.9 ± 11.9 μg/dl (x? ± SEM) at 2300 hours and a peak of 168.9 ± 7.8 μg/dl at 0900 hours. Conversely, a nadir in serum testosterone was noted at 0900 hours (117 ± 26.5 ng/ml) increasing to a peak of 328.5 ± 57.9 ng/ml at 0300 hours. Serum androstenedione and dehydroepiandrosterone followed a pattern similar to testosterone, with a serum androstenedione (176.4 ± 34.9 ng/ml) and dehydroepiandrosterone (11.7 + 1.8 ng/ml) nadir at 0900 hours and a plasma androstenedione (494.5 ± 55.4 ng/ml) and dehydroepiandrosterone (32.5 ± 4.1 ng/ml) peak at 0300 hours. Parallel changes of testosterone, androstenedione, and dehydroepiandrosterone suggest a significant contribution of all three androgens from a common site, the testes. In contrast to old world primates and humans, serum androstenedione levels exceeded serum testosterone levels in this species.     

Enantioselective gallopamil protein binding

The protein binding of the enantiomers of gallopamil has been investigated in solutions of human serum albumin, α₁-acid glycoprotein and serum. Over the range of concentrations attained after oral gallopamil administration, the binding of both enantiomers to albumin, α₁-acid glycoprotein, and serum proteins was independent of gallopamil concentration. The binding to both human serum albumin (40 g/liter) [range of fraction bound (f_b) R: 0.624 to 0.699; S: 0.502 to 0.605] and α₁-acid glycoprotein (0.5 g/liter) (range of f_b R: 0.530 to 0.718; S: 0.502 to 0.620) was stereoselective, favoring the (R)-enantiomer (predialysis gallopamil concentrations 2.5 to 10,000 ng/ml). When the enantiomers (predialysis gallopamil concentration 10 ng/ml) were studied separately in drug-free serum samples from six healthy volunteers the fraction of (S)-gallopamil bound (f_b: 0.943 ± 0.016) was lower (P < 0.05) than that of (R)-gallopamil (f_b: 0.960 ± 0.010). The serum protein binding of both (R)- and (S)-gallopamil was unaffected by their optical antipodes (f_b R: 0.963 ± 0.011; S: 0.948 ± 0.015) indicating that at therapeutic concentrations a protein binding enantiomer–enantiomer interaction does not occur. The protein binding of (R)- and (S)-gallopamil ex vivo 2 h after single dose oral administration of 50 mg pseudoracemic gallopamil (f_b R: 0.960 ± 0.010: predialysis [R] 6.9 to 35.3 ng/ml; S: 0.943 ± 0.016: predialysis [S] 9.5 to 30.7 ng/ml) was comparable to that observed in vitro in drug-free serum. Gallopamil metabolites formed during first-pass following oral administration, therefore, do not influence the protein binding of (R)- or (S)-gallopamil. © 1993 Wiley-Liss, Inc.     

Trace Elements in Obese Turkish Children

The quality of the diet of obese children is poor. Eating habits may alter micronutrient status in obese patients. In this study, we determined the serum levels of selenium, zinc, vanadium, molybdenum, iron, copper, beryllium, boron, chromium, manganese, cobalt, silver, barium, aluminum, nickel, cadmium, mercury, and lead in obese Turkish children. Thirty-four obese and 33 healthy control subjects were enrolled in the study. Serum vanadium and cobalt levels of obese children were significantly lower than those of the control group (0.244 ± 0.0179 vs. 0.261 ± 0.012 μg/l, p < 0.001, and 0.14 ± 0.13 vs. 0.24 ± 0.15 μg/l, p = 0.011, respectively). There was no significant difference between groups regarding the other serum trace element levels. In conclusion, there may be alterations in the serum levels of trace elements in obese children and these alterations may have a role in the pathogenesis of obesity.     

Association of Adenovirus Infection with Human Obesity

DHURANDHAR, NIKHIL V, PUSHPA R KULKARNI, SHARAD M AJINKYA, ABHAYA A SHERIKAR, RICHARD L ATKINSON. Association of adenovirus infection with human obesity. We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p<0.02) and body mass index (p<0.001) (95.1 ± 2.1 kg and 35.3 ± 1.5 kg/m², respectively) compared with the N-AGPT group (80.1 ± 0.6 kg and 30.7 ± 0.6 kg/m², respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p<0.02) and triglyceride (p<0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.     

Circulating isoflavonoid levels in CD-1 mice: effect of oral versus subcutaneous delivery and frequency of administration

The CD-1 mouse is a commonly used animal model to understand the biological effects of early-life exposure to soy isoflavones in infants. Most studies using CD-1 mice have administered isoflavones by daily subcutaneous injection, while infants receive oral feeds every few hours. The study objectives were to compare the total serum levels of genistein (GEN), daidzein (DAI) and the DAI metabolites equol and O-desmethyl-angolensin (O-DMA), after subcutaneous injection and oral dosing and to determine if frequency of oral administration results in different circulating levels of isoflavones using the CD-1 mouse model. From postnatal days 1 to 5, pups randomly received corn oil or soy isoflavones (total daily dose, 0.010 mg DAI+0.025 mg GEN) by subcutaneous injection once a day, orally once a day or orally every 4 hours. On postnatal day 5, 1 h posttreatment, mice were killed and serum was collected. Mice treated with soy isoflavones had higher (P<.05) serum GEN (female: 1895–3391 ng/ml and male: 483–578 ng/ml) and DAI (female: 850–1580 ng/ml and male: 248–322 ng/ml) concentrations versus control (5–20 ng/ml) mice, regardless of route or frequency of administration, and were similar among dosing strategies. Total serum concentrations of GEN and DAI were higher (P<.05) among females (GEN: 2714 ± 393 ng/ml and DAI: 1205 ± 164 ng/ml) than males (GEN: 521 ± 439 ng/ml and DAI: 288 ± 184 ng/ml) across treatment groups. Serum equol and O-DMA concentrations were negligible (<3 ng/ml) across groups. In conclusion, different routes of delivery and frequency of administration resulted in similar total serum levels of GEN, DAI¸ equol or O-DMA.     

Serum testosterone and musth in captive male African and Asian elephants

Testosterone concentrations in serum samples collected weekly over a 5-year period from a young adult male Asian elephant (Elephas maximus) and a young adult male African forest elephant (Loxodonta africana cyclotis) were measured by radioimmunoassay. Testosterone profiles during this maturational period were compared between the two species and related to the occurrence of musth, a recurring physiological and behavioral condition exhibited by most mature Asian, and some African, bull elephants. Musth is characterized by secretion from the bull's temporal glands, dribbling urine, and increased aggression. Serum testosterone concentrations in the Asian bull were elevated substantially between April and September each year, coincident with the presence of temporal gland secretion, urine dribbling, and aggressive behavior. Testosterone levels from April through September averaged (± SEM) 41.2 ± 2.8 ng/ml, compared to 7.6 ± 1.0 ng/ml during the rest of the year. In contrast, the testosterone profile of the African bull showed greater variation and lower levels overall, the only pattern being a tendency for levels to be lowest from November to February (avg. 6.8 ± 1.5 vs. 10.3 ± 0.8 ng/ml during the rest of the year). Temporal gland secretion and other signs of musth were first observed in this bull in 1988, at age 17. While his testosterone profile did not show a pattern comparable to that in the Asian bull, average testosterone values were significantly greater in 1988 compared to previous years. The Asian bull showed sexual attention to preovulatory (estrous) cows whether in musth or not, and exposure to estrous cows did not appear to alter the highly consistent, annual pattern of musth as evidenced in temporal gland flow.     

Steady-state pharmacokinetics of the enantiomers of citalopram and its metabolites in humans

The steady-state pharmacokinetics in serum and urine of the enantiomers of citalopram and its metabolites, demethylcitalopram (DCT) and didemethylcitalopram (DDCT), were investigated after multiple doses of rac-citalopram for 21 consecutive days (40 mg per day) to healthy human subjects who were extensive metabolisers of sparteine and mephenytoin. Comparable pharmacokinetic variability was noted for (+)-(S)-, (−)-(R)- and rac-citalopram. Enantiomeric (S/R) serum concentration ratios for citalopram were always less than unity and were constant during the steady-state dosing interval. A modest, but statistically significant, stereoselectivity in the disposition of citalopram and its two main metabolites was observed. Serum levels of the (+)-(S)-enantiomers of citalopram, DCT, and DDCT throughout the steady-state dosing interval investigated were 37 ± 6%, 42 ± 3% and 32 ± 3%, respectively, of their total racemic serum concentrations. The (+)-(S)-enantiomers of citalopram, DCT, and DDCT were eliminated faster than their antipodes. For (−)-(R)- and (+)-(S)-citalopram, respectively, the serum t½ averaged 47 ± 11 and 35 ± 4 h and AUC_ss averaged 4,193 ± 1,118 h · nmol/l and 2,562 ± 1,190 h · nmol/l. The observed enantiospecificities were apparently more related to clearance, rather than to distributional mechanisms. Chirality 9:686–692, 1997. © 1997 Wiley-Liss, Inc.     

Safety of Vitamin D Replacement in Patients with Primary Hyperparathyroidism and Concomitant Vitamin D Deficiency

ObjectiveTo evaluate the safety of vitamin D replacement in patients with vitamin D deficiency and primary hyperparathyroidism.MethodsRetrospective chart review of 35 patients from our endocrine clinic, age 22 to 89 years, diagnosed with primary hyperparathyroidism and vitamin D deficiency, and treated with either 1,000 to 2,000 international units (IU) of vitamin D daily or 50,000 IU of vitamin D weekly for 5 months. Data were collected before and after treatment on serum calcium, 25-hydroxyvitamin D (25-OH D), intact parathyroid hormone (iPTH), phosphorus, alkaline phosphatase, nephrolithiasis, fractures, and osteoporosis.Results25-OH D increased significantly, from a baseline of 14.65 ± 6.57 ng/mL to 42.17 ± 12.98 ng/ mL after weekly treatment with 50,000 IU of vitamin D (P<.0001), and from 22.42 ± 5.47 ng/mL to 33.33 ± 6.39 ng/mL following daily treatment with 1,000 to 2,000 IU of vitamin D (P<.0001). Pre- and posttreatment unadjusted serum calcium remained stable in the high-dose group (10.80 ± 0.43 mg/dL vs. 10.72 ± 0.67 mg/dL; P = .47), but decreased slightly in the low-dose group (10.76 ± 0.58 mg/dL vs. 10.11 ± 0.54 mg/dL; P = .0007). After adjusting for age, sex, vitamin D, and PTH levels, the small calcium difference in the low-dose group became statistically insignificant. Treatment with either high or low doses of vitamin D did not significantly change iPTH levels. Creatinine remained stable in all patients, and no new cases of nephrolithiasis were reported.ConclusionReplacing vitamin D in mild primary hyperparathyroidism is safe, effective, and does not increase calcium to dangerous levels. (Endocr Pract. 2013;19:420-425)