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The concentration of nitrite in seminal plasma does not correlate with sperm concentration, sperm motility, leukocytospermia, or sperm culture.

OBJECTIVE: To correlate the concentration of nitrite (the stable metabolite of nitric oxide) in seminal plasma with sperm number and motility, leukocytospermia, and sperm culture. DESIGN: Prospective study. SETTING: Academic research institution. PATIENT(S): Seventy normozoospermic or dyspermic men enrolled in an artificial insemination/in vitro fertilization program. INTERVENTION(S): Semen samples (n = 70) were checked for sperm concentration, total sperm count, sperm motility, seminal leukocyte concentration, and sperm culture; similarly, the concentration of nitrite in seminal plasma was measured by Griess reaction. MAIN OUTCOME MEASURE(S): Measurement of nitrite concentration in seminal plasma and its correlation with sperm concentration, total sperm count, sperm motility, leukocytospermia, and sperm culture. RESULT(S): The concentration of nitrite in seminal plasma does not correlate with sperm concentration, total sperm count, or with the proportion of immotile or rapid-forward motile spermatozoa. Moreover, the concentration of nitrite in seminal plasma is not significantly increased when sperm culture is positive, nor does it correlate with leukocyte concentration in semen. CONCLUSION(S): Our results do not support the hypothesis that in vivo nitric oxide synthesis affects sperm function; alternatively, our results could suggest that nitrite in the seminal plasma is not a sensitive marker of in vivo nitric oxide synthesis.

Fertilization in Vitro↗

Concentrations of the UV filter ethylhexyl methoxycinnamate in the aquatic compartment: a comparison of modelled concentrations for Swiss surface waters with empirical monitoring data.

UV filters in sunscreens and cosmetics protect the skin from damage through UV radiation. Many tonnes per year of UV filters are being used in Europe and will be present, at least seasonally, in detectable concentrations in surface waters similar to common pharmaceutically active substances. Predicted environmental concentrations (PECs) of ethylhexyl methoxycinnamate (EHMC; CAS 5466-77-3) were extrapolated for Switzerland, taking into consideration substance-specific environmental fate data and marketing estimates, by crude worst-case reckoning and by applying two environmental models (Mackay Level III; USES 3.0), both configured for Swiss hydrological and area data. By worst-case reckoning the summer PEC is 70.8-81.3 ng/l while for the remaining 8 months of the year the PEC is 13.1-15.1 ng/l. The Level III model results in concentrations of 2.4 ng/l during the summer and 0.44 ng/l during the rest of the year, while the USES 3.0 model gives an average PEC for the whole year of 7.6 ng/l. Pooling summer monitoring data (90 single analyses) from the River Rhine below Basel in the year 1997 (Water Protection Board of Basel) and from Lakes Zurich and Hüttner in 1998 (Poiger et al., in preparation) allowed a derivation of a probabilistic median concentration of 4.6 ng/l, a 95th-percentile concentration of 18.6 ng/l and a 99th-percentile concentration of 33.5 ng/l. The 6-fold range from the median value to the maximum calls for caution in interpreting published monitoring concentrations. Comparison of modelled PECs with realistic median concentrations shows that crude reckoning overestimates actual concentrations by a factor of about 10, probably through insufficient consideration of (further) degradation of EHMC in sewage works, surface waters, sediments or river banks. Both computer models, in contrast, are within the same order of magnitude as the actual summer concentrations. Based on the available data, both these environmental fate and distribution models give realistic PECs.

Cinnamates↗

Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors.

OBJECTIVES: The aim of this study was to investigate whether an increase in total homocysteine (tHcy) concentration with increasing age is due to diminishing serum concentrations of pyridoxal-5-phosphate (PLP), vitamin B-12, and folate. The possible influence of different lifestyle factors on tHcy concentration was considered. METHODS: Plasma tHcy, serum concentrations of pyridoxal-5-phosphate, vitamin B-12, and folate, intake of coffee and tea, alcohol, and methionine, as well as cigarette smoking, were determined in 252 elderly subjects (60-87 years old) of the longitudinal study on nutrition and health status in an aging population in Giessen (GISELA) and 99 young adults (20-34 years old) of the study on health and nutrition of young adults (GEJE). RESULTS: Mean plasma tHcy concentrations were significantly higher in elderly than in young female subjects (9.7 +/- 1.9 micromol/L vs. 9.0 +/- 1.6 micromol/L, p < 0.05), but there was no difference between elderly and young men (10.6 +/- 2.1 micromol/L vs. 10.7 +/- 2.6 micromol/L). No differences in tHcy were observed between young and elderly subjects after adjustment for serum concentrations of PLP, vitamin B-12, and folate. Multiple linear regression analysis revealed a significant influence of age only in elderly, but not in younger subjects. CONCLUSION: Higher tHcy concentrations in the elderly, in comparison to younger women, are due to lower serum concentrations of PLP, vitamin B-12, and folate, whereas within the age group of elderly subjects alone tHcy concentrations increase with age irrespective of serum vitamin concentrations.

Adult↗

Associations between concentrations of alpha- and gamma-tocopherol and concentrations of glucose, glycosylated haemoglobin, insulin and C-peptide among US adults.

Our objective was to study the cross-sectional associations between concentrations of alpha- and gamma-tocopherol and concentrations of glucose, glycosylated haemoglobin, insulin and C-peptide among US adults. We used data for 1289 participants without self-reported diabetes who were aged > or =20 years in the National Health and Nutrition Examination Survey 1999-2000. Alpha-tocopherol concentration was inversely associated with glucose concentration (beta per mmol/l=-0.01064, SE 0.00356, P=0.004) after adjusting for age, sex, race or ethnicity, education, smoking status, concentrations of total cholesterol and triacylglycerols, systolic blood pressure, waist circumference, alcohol use, physical activity, time watching television or videos or using a computer, and use of vitamin/mineral/dietary supplements. Among 659 participants who did not report using supplements, this association was no longer significant whereas the concentration of alpha-tocopherol was inversely associated with concentration of C-peptide (beta per mmol/l=-0.01121, SE 0.00497, P=0.024). Gamma-tocopherol concentration was positively associated with concentration of glucose (beta per mmol/l=0.09169, SE 0.02711, P=0.001) and glycosylated haemoglobin (beta per mmol/l=0.04954, SE 0.01284, P<0.001), but not insulin or C-peptide. The relationships between physiologic concentrations of the various forms of vitamin E and measures of glucose intolerance deserve additional investigation.

Adult↗

Development and validation of a new bitumen fume generation system which generates polycyclic aromatic hydrocarbon concentrations proportional to fume concentrations.

Bitumen fumes emitted during road paving and roofing contain polycyclic aromatic compounds (PACs) of potential health concern. Little information is available for an experimental device devoted to inhalation experiments with animals exposed to bitumen fumes, and in all studies the systems were never validated for a range of fume concentrations, which prohibited their use for toxicological concentration-effect studies. Therefore, the purpose of this study was to validate a new experimental device able to generate bitumen fumes at different total particulate matter (TPM) concentrations with a linear correlation between TPM and the concentrations of different PACs, thus allowing toxicological dose-response studies with fumes representative of those in the field. Atmosphere samples collected from an animal exposure chamber allowed the determination of TPM, toluene soluble matter, polycyclic aromatic hydrocarbons (PAHs) and semi-volatiles. The particulate size distributions were determined in order to assess the deposition pattern in the respiratory tract. The temperature of 170 degrees C was chosen by analogy with the upper range of the temperature used during paving operations. The temperature of the air passing over the fume emission area was regulated to 20 degrees C and stirring of the heated bitumen was restricted to 90 r.p.m. The data show that the objective of developing a static fume generation system that reproducibly produces fumes in the inhalation chamber for specified target concentrations (TPM) were successful. The within-day variation coefficients for TPM were between 2.5 and 6.1%. The day-to-day variations for TPM concentration were between 4.1 and 5.8%. The concentrations of the 4-5 ring PAHs and the polycyclic aromatic sulphur heterocycles were proportional to the TPM concentration. The 2 and 3 ring PAH concentrations showed a deviation from proportionality with the TPM, probably due to their re-evaporation during sampling. The mass median aerodynamic diameter of airborne particles varied from 1.4 micro m at a fume concentration of 5 mg/m(3) to 3.2 micro m at 100 mg/m(3). In conclusion, this equipment was suitable for nose-only inhalation studies in the 5-100 mg/m(3) range of TPM. Bitumen fumes were generated with a good reproducibility under well-controlled conditions. Finally, the PAH profiles from atmospheric samples were in good agreement with those measured during road paving.

Hydrocarbons↗

The confounding effects of age, gender, serum creatinine, and electrolyte concentrations on plasma B-type natriuretic peptide concentrations in critically ill patients.

OBJECTIVE: To investigate the confounding effects of age, gender, serum creatinine, and electrolyte concentrations on plasma B-type natriuretic peptide (BNP) concentrations in critically ill patients. DESIGN: A prospective cross-sectional study. SETTING: A 20-bed general intensive care unit of a tertiary referral hospital. PATIENTS: Patients were 121 patients admitted to the intensive care unit over a period of 9 wks. INTERVENTIONS: Intravenous blood was collected for BNP measurements, and cardiac investigations including echocardiography were carried out for every patient on admission. MEASUREMENTS AND MAIN RESULTS: The mean BNP concentration was 201 +/- 317 pg/mL (n = 121). Thirty-five patients (28.9%), identified to have cardiac abnormalities, exhibited higher BNP concentrations than those without cardiac abnormalities (518 +/- 394 vs. 60 +/- 98 pg/mL, p <.001). The females exhibited higher concentrations of BNP than males in the noncardiac abnormality group (96 +/- 132 pg/mL, n = 39 vs. 31 +/- 38 pg/mL, n = 47, p =.016). BNP correlated significantly with age (r2 =.19) and creatinine (r2 =.084). The latter correlation became insignificant when patients with cardiac abnormality were excluded. No correlation was found between serum Na+ and K+ concentrations with BNP. Multivariate analyses demonstrated that the presence of cardiac abnormalities accounted for nearly 50% of the BNP variation. Addition of age and gender improved R2 to 60%. The contribution of creatinine was found to be insignificant. There was no association between BNP concentrations and serum Na+ and K+ concentrations. Logistic analysis confirmed that BNP is the strongest predictor for cardiac abnormalities in the critically ill patients. CONCLUSION: The current study demonstrated that plasma BNP concentrations increased with age and were higher in females than in males. Although the presence of cardiac disease was the most important determinant for BNP variations, age and gender also contributed significantly. The results suggest that age and gender need to be taken into account in the interpretation of BNP concentrations in critically ill patients.

APACHE↗

Do saliva concentrations predict plasma unbound theophylline concentrations? A problem re-examined.

On the assumption that plasma unbound drug concentrations are therapeutically active, the value of saliva concentrations in predicting plasma unbound theophylline concentrations was investigated in 25 ambulatory adults (aged 27 to 84 years) receiving theophylline (225-1350 mg aminophylline daily) for asthma or chronic bronchitis. Plasma samples from all patients were ultrafiltered, and the plasma unbound theophylline (F) concentrations were compared with the corresponding total plasma (P), citric acid stimulated saliva (S) and non-stimulated saliva (Ns) theophylline concentrations. Plasma unbound theophylline concentrations correlated significantly with P (r = 0.97) and S (r = 0.973), but less well with Ns (r = 0.883), emphasising the benefit of saliva stimulation. The ability of S to predict F theophylline concentrations was assessed using the mean ratio of 0.7297. In 92% of the patients, predicted F concentrations were within +/- 1 microgram/ml of the measured concentrations. Similarly, using the mean F/P ratio of 0.418, predicted P were within +/- 1 microgram/ml of obtained P in 84% patients, and using the mean S/P ratio of 0.568, predicted P were within +/- 1 microgram/ml of obtained P in 81%. An accuracy of +/- 1 microgram/ml in estimating F from S concentrations would be sufficient to indicate appropriate dose adjustments, and we therefore advocate the use of stimulated saliva samples for routine monitoring of theophylline therapy.

Adult↗

[An experimental examination of the significance of the peak antimicrobial concentration value in urine and time above MIC on the effect of antimicrobial agents--an examination using a severely complicated in vitro bladder model with an autosimulation system for antimicrobial concentration in urine].

Using a severely complicated in vitro bladder model with a computer-controlled autosimulation system for antimicrobial concentration in urine, we examined the significance of the peak concentration value and time above MIC, and obtained the following results. 1. Regarding the initial bactericidal speed, the higher the peak concentration value was, the more quickly the bacterial concentration decreased. 2. Concerning the minimum value of bacterial concentration in the model bladder, the higher the peak concentration value was, the more the level tended to decrease. 3. Regarding inhibition of regrowth of bacteria (ERT) 1) When a particular antimicrobial agent had no PAE on bacteria, the viable bacterial count curve was similar in cases of peak antimicrobial concentration values of higher than 8 MIC. 2) On the other hand, when an antimicrobial agent had PAE on bacteria, regrowth of bacteria occurred quickly below a certain peak concentration (24 MIC or 64 MIC value), although there was some difference depending on the type of antimicrobial agents. Thus, it was suggested that the peak concentration above that level be attained and maintration above that level be attained and maintained for some time were in order to obtain PAE adequately. 4. It is concluded from the aforementioned facts that two factors, a certain high concentration and a certain continued time are necessary for both antimicrobial agent with metabolic disorder and antimicrobial agent with cell wall synthetic inhibition to obtain proper antimicrobial effect. The condition of their necessity differed slightly according to the two different agents.

Adult↗

Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations.

OBJECTIVE: To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN: Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING: Urban Shanghai, China. SUBJECTS: 9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE: Death from coronary heart disease and other causes. RESULTS: The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION: Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death.

Cerebrovascular Disorders↗

Rapid decreases in adrenal and plasma corticosterone concentrations after drinking are not mediated by changes in plasma adrenocorticotropin concentration.

Rats given water to drink only during a brief daily period respond to water presentation with a rapid decline in plasma corticosterone concentration. To determine whether this response is consequent to a decrease in plasma ACTH concentration or whether it reflects a sudden reduction in adrenal responsiveness to ACTH, we allowed rats access to water for 2 h/day at lights on and measured plasma ACTH and adrenal and plasma corticosterone concentrations at 3- or 5-min intervals after the onset of drinking. Adrenal and plasma corticosterone concentrations decreased significantly within 2-3 min after water presentation in the absence of concomitant changes in plasma ACTH concentration. The effect was apparent by 5 days after initiating the restricted drinking schedule and became stronger with time up to 21 days. Further characterization of the response showed that the in vitro corticosterone secretion of adrenals removed at intervals after water presentation followed the same pattern as the in vivo concentration. When empty water bottles were presented, plasma ACTH and corticosterone concentrations increased. Neither adrenal medullary function nor plasma renin concentration was found to be associated with the decline in adrenal responsiveness to ACTH after drinking. Hemisection of the spinal cord of unilaterally adrenalectomized rats attenuated the corticosterone response regardless of whether the hemisection was contralateral or ipsilateral to the remaining adrenal. These data suggest that the decreases in plasma and adrenal corticosterone concentration occurring after drinking in water-restricted rats are not dependent on changes in plasma ACTH concentrations, but may be related to changes in adrenal blood flow, steroid metabolism and distribution, or neural input to the adrenal cortex.

Adrenal Cortex↗

Effect-site concentration of propofol for recovery of consciousness is virtually independent of fentanyl effect-site concentration.

UNLABELLED: Fentanyl reduces the amount of propofol necessary to prevent responses to surgical stimuli. However, opioids have relatively little effect on consciousness. We, therefore, tested the hypothesis that fentanyl minimally alters the effect-site concentration of propofol associated with awakening. Fifty women having gynecologic laparotomy with propofol anesthesia were randomly allocated into the following target effect-site fentanyl concentrations: 0.8, 1.0, 1.4, 2.0, and 3.0 ng/mL. Fentanyl was continued at the designated rate through the initial postoperative phase. The propofol effect-site concentration associated with eye opening in response to verbal command was regarded as the awakening concentration. The estimated propofol effect-site concentrations at awakening did not differ significantly among the groups and were 1.9 +/- 0.5 micro g/mL with a fentanyl effect-site concentration of 0.8 ng/mL; 1.6 +/- 0.4 micro g/mL with 1.0 ng/mL of fentanyl; 1.6 +/- 0.2 micro g/mL with 1.4 ng/mL of fentanyl; 1.7 +/- 0.4 micro g/mL with 2.0 ng/mL of fentanyl; and 1.6 +/- 0.34 micro g/mL with 3.0 ng/mL of fentanyl (mean +/- SD). Seventy percent of the subjects in the 0.8 ng/mL fentanyl group spontaneously complained of pain, whereas none of the patients in the 2 or 3 ng/mL groups did. Five (56%) of 9 women in the 3 ng/mL group had a postoperative respiratory rate <6 breaths/min. Heart rate in one of these women decreased to <40 bpm. These data suggest that the optimal fentanyl effect-site concentration in patients recovering from gynecologic laparoscopy is between 1.4 and 2.0 ng/mL. IMPLICATIONS: The effect-site concentration for propofol at awakening was virtually independent of the fentanyl effect-site concentration over the range of 0.8 to 3.0 ng/mL; however, 0.8 ng/mL of fentanyl was associated with inadequate postoperative analgesia, and 3.0 ng/mL of fentanyl was associated with respiratory toxicity. The optimal postoperative fentanyl effect-site concentration during recovery from propofol general anesthesia for laparotomy thus appears to be near 2 ng/mL.

Adult↗

Plasma renin activities, angiotensin II concentrations, atrial natriuretic peptide concentrations and cardiopulmonary function values in dogs with severe heartworm disease.

Relationships among plasma renin activities (PRA), plasma angiotensin II (ATII) concentrations, atrial natriuretic peptide (ANP) concentrations and cardiopulmonary function values were examined in dogs with ascitic pulmonary heartworm disease and acute- and chronic-vena caval syndrome (CS). PRA, plasma ATII concentration and plasma ANP concentration tended to be higher or were significantly higher in dogs with ascites, acute- and chronic-CS. PRA correlated significantly with plasma ATII concentration, WBC count, ALP activity, plasma concentrations of urea nitrogen, creatinine, sodium, potassium, and chloride, right ventricular endodiastolic pressure and right atrial pressure. Plasma ATII concentration correlated significantly with WBC count, plasma concentrations of urea nitrogen, sodium, and potassium, right ventricular endodiastolic pressure and right atrial pressure. Plasma ANP concentration did not correlate with PRA or ATII concentration, but correlated significantly only with pulmonary arterial pressure.

Angiotensin II↗

Circulating peptide YY concentrations are higher in preterm than full-term infants and correlate negatively with body weight and positively with serum ghrelin concentrations.

BACKGROUND: Peptide YY (PYY) and ghrelin are gastrointestinal tract-derived hormones that play roles in the regulation of food intake and energy balance. Negative energy balance often occurs in hospitalized preterm infants. METHODS: To measure serum concentrations of PYY in preterm and full-term infants and to investigate their correlations with anthropometric characteristics, food intake, and serum ghrelin concentrations, we measured serum PYY and ghrelin concentrations by RIA in 62 healthy preterm infants [mean (SD) gestational age, 32.0 (2.1) weeks; postnatal age, 40.9 (14.8) days] and 15 healthy full-term infants of comparable postnatal age. All of the infants were formula-fed every 3 h. RESULTS: PYY concentrations were significantly higher in preterm [1126.2 (215.4) ng/L] than in full-term infants [825.3 (234.4) ng/L; P < 0.001]. In the entire study population, serum PYY concentrations correlated negatively with gestational age and anthropometric measurements (birth weight, body weight, body length, body mass index, and head circumference) and positively with serum ghrelin concentrations, whereas there was no significant correlation between PYY concentration and caloric intake or weight gain. Multiple regression analysis, after correction for prematurity, revealed that serum PYY concentrations correlated independently with serum ghrelin concentrations and infant body weight or body mass index. CONCLUSIONS: Circulating concentrations of PYY may increase in preterm infants to compensate for the negative body-weight balance. The physiologic mechanisms behind the correlation between PYY and ghrelin remain to be elucidated.

Anthropometry↗

Circulating concentrations and pattern of luteinizing hormone and follicle-stimulating hormone in circulation are changed by the circulating concentration of 17 beta-estradiol in the bovine male and female.

The objectives of the present study were 1) to determine whether 17 beta-estradiol (E2) regulation of tonic secretion of LH and FSH is sexually differentiated in the bovine and 2) to evaluate the effects of various physiological concentrations of E2 on the profiles and concentrations of gonadotropins in circulation. This was accomplished by administering different numbers of implants containing E2 to gonadectomized bovine males and females. Mean age at initiation of the study was 18.5 mo. Animals received 1, 2, 4, 8, or 16 implants of E2 or a sham implantation. Mean concentrations of LH in circulation and amplitude of LH pulses were similar between males and females after administration of E2. There was a cubic response for mean concentrations of LH and amplitudes of LH pulses across the dosages of E2 administered; lower concentrations of E2 had little effect, whereas higher concentrations of E2 suppressed both mean LH and amplitude of LH pulses. A linear decline in frequency of LH pulses occurred as concentrations of E2 in circulation increased. A treatment x sex interaction resulted for mean concentrations of FSH in circulation. Low doses of E2 resulted in a greater enhancement of circulating concentrations of FSH in males than in females. Tonic secretion of LH in bovine males and females responded in a similar manner to administration of various physiological concentrations of E2; however, a differential response between sexes was observed for FSH.

Animals↗

Balance and serum concentration of biotin in sheep fed alfalfa meal-based diets with increasing level of concentrate.

The objective of this study was to test the hypothesis that serum biotin concentration and biotin balance (consumed - [urinary output + fecal output]) measured as total avidin-binding substances (biotin + biotin metabolites) are responsive to changes in the proportions of dietary alfalfa meal and concentrate fed to sheep. Eight sheep (initial BW = 40 kg) consumed a pelleted alfalfa meal-based diet that had 95:5, 48:52, 23:77, or 9:91% alfalfa meal:concentrate ratios (DM basis) in a replicated 4 x 4 Latin square design with 20-d periods (10 d of acclimation, 7 d of adaptation, and a 3-d collection period with jugular blood drawn on the last day). Replacing alfalfa meal with concentrate in the pelleted diets decreased dietary concentrations of biotin proportionally. As the percentage of alfalfa meal in the diet decreased, there was a linear decrease in daily DM intake (1,128 to 901 g of DMI/d; P < 0.01), with a linear (P < 0.01) and quadratic (P < 0.01) increase in the apparent total-tract DM digestibility of diets (51.0 to 80.0%). The biotin consumed decreased with alfalfa meal proportion in the diet (linear, P < 0.01). Both fecal biotin concentration (linear, P < 0.01) and fecal biotin output (quadratic, P < 0.05) increased, reaching peaks at 23% alfalfa meal. Fecal biotin output was not correlated with biotin intake, DMI, or intake of digestible DM. Mean urinary output, urinary biotin concentration, urinary biotin output, and serum biotin concentration were not affected by treatments. Means of biotin balance were negative and revealed the same trends among treatments as did fecal output. Biotin balance was a quadratic (P < 0.05) function of decreasing alfalfa meal in the diet, with more negative values at the alfalfa meal:concentrate ratio of 23:77. Results suggest that the greatest synthesis of biotin in the total digestive tract occurs with diets of either 52 or 77% concentrate for sheep; however, research addressing the significance of biotin metabolites on biotin balance and plasma biotin pool is needed.

Animal Feed↗

Prospective study on concentration-efficacy and concentration-toxicity: correlations with lamotrigine serum levels.

RATIONALE: The relationship between lamotrigine (LTG) serum concentration and clinical response in patients with epilepsy is still controversial. We therefore performed a prospective study in which LTG was added to the existing therapeutic regimen in patients with poorly controlled epilepsy. The goal of the study was to determine the serum levels of patients with seizure reduction of at least 50% after addition of LTG, and to assess a possible relationship between the occurrence of adverse effects due to LTG and its serum concentration. METHODS: Fifteen adult patients were evaluated with respect to seizure reduction. Nine patients had focal seizures with or without generalization, six patients had generalized seizures (Group I). The correlation between the occurrence of adverse effects and LTG serum concentration was calculated in a second group of 63 young adult, and adult patients with epilepsy (Group II). RESULTS: The range of the LTG serum concentration in the 15 patients with a 50% or greater reduction of seizure frequency was 1.3-7.1 microg/ml (median = 3.6 microg/ml). In group II patients the serum concentration associated with an adverse effect was not significantly different from the serum concentration in patients without adverse effects. There was, however, a tendency for higher serum concentrations in patients with adverse effects. In the serum concentration range of 5 to 13 microg/ml, the frequency of LTG levels which were accompanied by an adverse effect increased only slowly, whereas above 13-14 microg/ml, there was a steep increase in adverse effects. The serum concentration of four patients with tremor (mean = 14 +/- 2.8 microg/ml) was significantly higher than the LTG level which were in 42 patients who did not have adverse effects at any time (mean = 4.8 +/- 4.1 microg/ml), P = 0.003. CONCLUSION: Our results suggest a target range for LTG serum concentrations of 1-13 microg/ml, especially, if LTG is used as an add on-drug.

Adolescent↗

[Studies on tissue concentrations of cefoperazone and piperacillin classified by the site of the wall of gallbladder and concentration of piperacillin in the bile after operation].

In selection of drugs to be used in the treatment of biliary tract infections, sensitivity of causative organisms to drugs and tissue concentrations of the drugs constitute important factors. In the present study we treated patients with cholelithiasis with cefoperazone (CPZ) and piperacillin (PIPC), both of which have been reported to show high concentrations in the bile, and concentrations of the drugs in serum, cholecystic bile and various sites of the wall of gallbladder were determined. In addition the drug concentrations in the serum and bile at the 1st and 7th postoperative days were also determined. The following results were obtained. Comparison of concentrations of CPZ and PIPC at various sites of the wall of gallbladder revealed that both drugs showed high levels in the bottom, body and neck areas of the gallbladder with no difference by sites. The concentration ratios against serum for these drugs were 71.8 and 83.6%, showing good transference into tissue. The mean concentrations of CPZ and PIPC in the cholecystic bile were as high as 448.8 and 381.6 micrograms/ml, the ratio against serum being about 4:1. The serum concentrations of PIPC at the 1st and 7th postoperative days were 116 and 137 micrograms/ml at 60 minutes after starting drip infusion, with no difference between these 2 days. In the bile concentrations of PIPC on both postoperative days showed the peak levels of 2,587 and 1,157 micrograms/ml at 120 minutes after starting drip infusion. The concentrations at the 1st postoperative day were higher. The recovery rate of PIPC from the bile was also higher at the 1st postoperative day. From the results that both drugs showed high levels in the wall of gallbladder and also showed high levels in the bile immediately after the operation, PIPC and CPZ are considered to be effective drugs for biliary tract infections.

Bile↗

A comparison of the concentrations of certain chlorinated hydrocarbons and polychlorinated biphenyls in bone marrow and fat tissue of children and their concentrations in breast milk.

Chlorinated hydrocarbon (CHC) and polychlorinated biphenyl (PCB) concentrations in the bone marrow of 57 children were compared with the concentrations in adipose tissue of 50 children and the concentrations in breast milk in the Federal Republic of Germany from 1984 to 1991. The concentrations of hexachlorobenzene (HCB), the dichlorodiphenyltrichloroethane (DDT)-metabolites, and polychlorinated biphenyl (PCB) congeners no. 138 and no. 153 were increased threefold, while the concentrations of several hexachloro-cyclohexane (HCH)-isomers and PCB congener no. 180 were only increased twofold. Because breast feeding is the primary source of CHC and PCB in toddlers and infants we also compared the concentrations in bone marrow of children with the concentrations in breast milk and found approximately fourfold higher concentrations for the most highly chlorinated PCB congener no. 180, but only threefold higher concentration for PCB 138 and 153 and the DDT-metabolites. The concentrations of beta-HCH and HCB were only slightly higher in bone marrow.

Adipose Tissue↗