Total Blood Samples Research Articles

Effect of polymorphism on in vitro-in vivo properties of carbamazepine conventional tablets

The objective of the present study was to investigate the effect of polymorphism on in vitro-in vivo properties of carbamazepine (CBZ). For this purpose, three different polymorphs and a dihydrate of CBZ were obtained and the conventional tablets of these crystalline forms at the dose of 200 mg were prepared. The polymorphs were examined by the IR and DSC analysis. The tablets were investigated by the in vitro dissolution test. Tegretol was selected as a reference. The tablets of β CBZ demonstrated the lowest dissolution rate, while the α form tablets exhibited the highest. Dissolution rates were significantly changed by the polymorphic forms of CBZ. Tegretol, bulk powder and β CBZ tablets were selected for the bioavailability study. Six healthy volunteers participated in an open-randomized cross-over designed clinical trial. After a total blood sampling period of 96 h, plasma levels of CBZ were determined by HPLC analysis by using a CN column and an acetonitril-water (30:70) mobile phase. There were no significant differences between the plasma concentration-time curves of Tegretol, bulk powder and β CBZ tablets. The only marked difference was the time required to reach plasma peak concentrations.

Simultaneous onset of acute inflammatory response, sepsis-like symptoms and intestinal mucosal injury after cancer chemotherapy.

Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5-fluorouracil (5-FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus-amebocyte-lysate test. In the 5-FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFalpha and IL-6 were seen to increase, peaking at day 6 (IL-6, 350.0 +/- 67.8 pg/ml; TNFalpha, 26.1 +/- 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5-FU group showed dramatic sepsis-like manifestations, whereas the control group did not. Within the 5-FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis-like manifestations after systemic chemotherapy.

A new ultrasound principle for characterizing erythrocyte aggregation: in vitro reproducibility and validation.

There is no method currently available to quantify erythrocyte aggregation in vivo. In this work, using a Couette system, we defined new ultrasound indexes potentially applicable for non-invasive investigations. Two ultrasound protocols were developed: (1) a protocol in which decreasing shear rates ranging from 200 to 1 s-1 were applied to solutions; and (2) a protocol in which a 200 s-1 shear rate was initially applied followed by stoppage of flow (a kinetics protocol). New ultrasound indexes were defined as: the power PUS at the nominal frequency of each transducer, Rayleigh's slope (tangent of the curve PUS = f(log(F)) through the 3.5 to 15 MHz frequency bandwidth) and kinetic indexes characterizing the aggregation/aggregability of the suspension. Using washed erythrocytes resuspended in saline, it was shown that the ultrasound intensity is dependent at 3.54 +/- 5.9% (NS) to the power of the frequency (theoretical value = 4). Using 10 total blood samples extracted from a single pig, good reproducibility for all indexes (5%) was demonstrated. A suitable and reproducible methodology was developed and validated for studying erythrocyte aggregation in calibrated in vitro conditions.

DNA damage-related RNA expression to assess individual sensitivity to ionizing radiation.

Predictive markers of intrinsic radiosensitivity in healthy individuals are needed in monitoring their occupational or environmental radiation exposure and may predict a patient's response to radiotherapy. Ionizing radiation can induce a large spectrum of DNA lesions, but under optimal DNA repair conditions, the principal residual lesions of importance are misrepaired double-strand breaks. The micronucleus (MN) assay represents a useful test in measuring radiosensitivity since it reflects non-repaired DNA breaks at the time of cell division. Spontaneous and radiation-induced MN vary greatly between individuals, and little is known about the molecular mechanisms of this variability. DNA repair and apoptosis processes are involved in the cellular response to radiation-induced DNA damage, and variation in gene expression related to these cellular pathways could be linked to individual radiosensitivity. In this study we analysed by real-time quantitative RT-PCR the basal expression of 12 genes involved both in DNA repair and apoptosis in a series of blood samples obtained from 32 healthy male donors. Relationships between basal RNA expressions and MN frequency and distribution per bi-nucleated cell were studied after ex vivo irradiation of total blood samples. Our results indicate that the variability of mRNA gene expression among the 32 subjects appears to be of the same magnitude or higher than that found for spontaneous or radiation-induced MN frequency and that RAD51 gene expression is negatively correlated with radiation-induced MN frequency.

Sequential V(A)/Q distributions in the normal rabbit by micropore membrane inlet mass spectrometry.

We developed micropore membrane inlet mass spectrometer (MMIMS) probes to rapidly measure inert-gas partial pressures in small blood samples. The mass spectrometer output was linearly related to inert-gas partial pressure (r(2) of 0.996-1.000) and was nearly independent of large variations in inert-gas solubility in liquid samples. We infused six inert gases into five pentobarbital-anesthetized New Zealand rabbits and used the MMIMS system to measure inert-gas partial pressures in systemic and pulmonary arterial blood and in mixed expired gas samples. The retention and excretion data were transformed into distributions of ventilation-to-perfusion ratios (V(A)/Q) with the use of linear regression techniques. Distributions of V(A)/Q were unimodal and broad, consistent with prior reports in the normal rabbit. Total blood sample volume for each VA/Q distribution was 4 ml, and analysis time was 8 min. MMIMS provides a convenient method to perform the multiple inert-gas elimination technique rapidly and with small blood sample volumes.

The effects of medium-strength electric impulses on human blood

Leukocyte subsets, total leukocyte isolates or full blood samples were subjected to medium-strength square-wave electric impulses (100 V/cm field force, 5 ms duration). On the surface of the leukocytes, the expressions of several markers (CD3, CD4, CD8, CD11a, CD11b and ICAM-1) were determined in order to study the influence of pulsed ionic currents on different aspects of the cellular immune response. Large individual differences were observed among randomly chosen healthy donors, both in the initial expression rate and in the response patterns of different antigens. As a general conclusion, it can be stated that electric impulses with the above parameters activate the state of immune response alertness of human leukocytes. Changes in the activities of several enzymes in the serum in response to electric impulses were also tested in order to examine the feasibility of ex vivo electric treatment of human blood for the establishment of an antiviral and immune activated condition. Slightly elevated lactate dehydrogenase (LDH) levels point to a possibility of enhanced haemolysis, while the lack of an elevation in the membrane-bound peroxidase activity indicates the absence of haemolysis. Significant rises were detected in the serum superoxide dismutase (SOD) activities. Since most ex vivo blood manipulations are characterised by the appearance of superoxide radicals in the serum, a SOD activity enhancement is considered beneficial in these cases. A mild, but significant reduction in the blood clotting time indicates that electric treatment of human blood should be performed with special attention to thrombosis-prone conditions, and adequate precautions and countermeasures should be introduced. Although wider examinations are required before this method can be fully recommended, ex vivo blood treatment with medium-strength electric impulses seems to be a promising adjuvant course for the establishment of acute immune potentiation and an antiviral state in patients undergoing dialysis treatment.

Peripherally inserted central venous catheters (PICC)

Venepuncture and repeated peripheral venous cannulations are the most frequently performed painful procedures in hospitalized children, resulting in an unpleasant experience for both the child and parents.1 Peripheral cannulae are short lasting, easily dislodged and can be difficult to maintain. On the other hand, tunnelled catheters are invasive, require specialized expertise and may be associated with significant risks and costs.2 Aim: To evaluate the role of peripherally inserted central venous catheters (PICC) for intermediate term venous access in hospitalized children. Methods: A prospective descriptive study, evaluating insertion of PICC in hospitalised children requiring venous access for intermediate term (7 days to 2 months). Silicon catheters were inserted in the antecubital fossa under strict aseptic conditions using a modified Seldinger technique under appropriate sedation and analgesia.3 Pain experienced during insertions, was quantified using validated pain scales.4 During the course of the study, a sample of children (n = 55) requiring peripheral venous cannulation (PVC) was also studied as a cohort for comparison of pain experienced during the procedures. Results: PICC insertion was attempted in 90 patients (median age 4 years; range 8 days – 16 yr) over a period of 18 months, between October 1997 and April 1999 with a success rate of 92%. Median time for procedure was 45 min (range 15–210). Median pain scores as assessed by nurses and parent/child were 1 (1– 5) and 2 (0–4) respectively. Therapy was completed in 75 (83%) patients with PICC. Fifteen PICC were prematurely removed. Median length of timein situ was 10 days, a total of 1081 catheter days. There were no cases of clinically detectable thrombotic complications or PICC related sepsis. Coagulase-negative staphylococci were grown from 8/90 (9%) catheter tips. PICC were used for intravenous antimicrobials, total parenteral nutrition, blood transfusions, erythropoetin and blood sampling (n = 529). In addition, 55 patients (median age 2 years; range 10 days – 17 yr) subjected to peripheral venous cannulations (PVC) were also evaluated. Median time for procedure was 10 min (1–60) with median pain scores of 2 (1– 5) and 3 (0–4) by nurses and parent/child respectively. Conclusions: PICC provide an effective alternative to repeated peripheral venous cannulations and can be inserted by designated trained medical and nursing team with a high success rate. PICC are long lasting, better tolerated, allow repeated blood sampling, have few complications and may facilitate home care for some patients. PICC should be the vascular access of choice for adults and children requiring intermediate-term vascular access and intensivists have a role in setting up and providing this service in the UK.

Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats.

1. The aim of this work was to study the influence of the metabolic control, estimated by the levels of glycosylated haemoglobin in total blood samples (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced diabetic rats. Four groups of animals with different levels of insulin treatment were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to 12% and > 12%, respectively. 2. The parameters analysed were: (1) the endothelium-dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in aorta: and (3) the existence of oxidative stress by studying the influence of the free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to both ACh and NO. 3. In both isolated aortic segments and mesenteric microvessels, the endothelium-mediated concentration-dependent relaxant responses elicited by ACh were significantly decreased when the vessels were obtained from diabetic animals but only with HbA1c values higher than 7.5%. There was a high correlation between HbA1c levels and the impairment of ACh-induced relaxations, measured by pD2 values. 4. The concentration-dependent vasorelaxant responses to NO in endothelium-denuded aortic segments were significantly reduced only in vessels from diabetic animals with HbA1c values higher than 7.5%. Again, a very high correlation was found between the HbA1c values and pD2 for NO-evoked responses. 5. In the presence of SOD, the responses to ACh or NO were only increased in the segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels <7.5%). 6. These results suggest the existence of: (1) a close relation between the degree of endothelial dysfunction and the metabolic control of diabetes, estimated by the levels of HbA1c; and (2) an increased production of superoxide anions in the vascular wall of the diabetic rats, which is also related to the metabolic control of the disease.

Pharmacokinetics of factor IX in patients with haemophilia B

The aims of this study were to investigate the influence of total blood sampling time on the estimated pharmacokinetic parameters of Factor IX procoagulant activity (FIX:C) and to relate the pharmacokinetics of FIX:C to the putative physiological disposition of Factor IX (FIX). Six patients with severe haemophilia B each received 2 infusions of FIX and on both occasions blood samples were collected for 104 h. Each FIX:C decay curve was processed with successive deletion of the last (remaining) datapoint. The fitted terminal half-life (t1/2 beta) and the calculated model-independent mean residence time (MRTMI), elimination clearance (CLMI) and volume of distribution at steady state (Vss) stabilised close to their final values when FIX:C data corresponding to at least 56 h of sampling were used. The final mean values were t1/2 beta = 34 h, MRTMI = 37 h, CLMI = 4.0 ml.h-1.kg-1 and Vss = 0.15 l.kg-1. The disposition of FIX could be characterised by a two-compartment pharmacokinetic model. On average, FIX molecules spent 44% of their total MRT in the second (or "extravascular") compartment. The distribution clearance was comparable to estimated total lymph flow. The volume of the central compartment was twice the estimated plasma volume, which may reflect the rapid and reversible binding of FIX to vascular endothelium. This explains the common clinical finding that the peak activity of FIX:C is less than the injected dose divided by the estimated plasma volume of the patient.

Bioavailability of a new sustained‐release theophylline capsule in fasted and non‐fasted healthy subjects: Single and multiple dosing studies

Eighteen healthy, non-smoking, adult volunteers participated in single and multiple dose three-way crossover studies to evaluate a sustained-release, pellet-filled capsule of theophylline, Austyn. The effect of food on the bioavailability of the sustained-release capsule was investigated by administering 300 mg single doses of Austyn, with a high-fat meal and without food and a divided 300 mg dose of the reference product Elixophyllin elixir, given after fasting. Plasma theophylline concentrations were measured by fluorescence polarization immunoassay (FPIA) which had been validated against HPLC. The single dose study data showed that there were no significant differences (n = 18, ANOVA, p greater than 0.05) between the three regimens with respect to AUC0-infinity values (mg h l-1), (mean +/- SD); Elixophyllin fasting = 97.1 +/- 33.7, Austyn with food = 90.9 +/- 31.3, Austyn fasting = 91.2 +/- 33.8. Similarly, multiple dosing with rapid-release Nuelin tablets, Austyn capsules, and sustained-release Theo-Dur tablets demonstrated that there were no significant differences between regimens with respect to AUC0-24h, AUC0-12h, and AUC12-24h values calculated from the steady-state concentrations (5th day, 24 h sampling). However, the percentage fluctuation at steady-state over the total blood sampling period was significantly less for treatment with the sustained-release capsule. Austyn, compared with the sustained-release tablet, Theo-Dur (Austyn = 36.7 +/- 13.7 per cent, Theo-Dur = 53.1 +/- 14.1 per cent). The results of the single and multiple dose studies indicate that Austyn capsules demonstrate complete bioavailability, and good controlled release characteristics not influenced by concomitant intake of a high-fat meal and with no evidence of dose dumping.

Determination of bromide ions in total blood, plasma and urine by ion chromatography with amperometric detection

A direct injection method is described for the determination of bromide ions in plasma and urine by ion chromatography. After being diluted 10-20 times with eluent, the sample was directly injected into an ion chromatograph equipped with amperometric detection. Calibration curves were obtained in the range of 0.05 to 5 micrograms/ml of bromide ions. The coefficient of variation was calculated to be in the range of 1.3-9.4% for 10 repeated measurements and recovery was over 93%. The correlation between analytical results by the proposed method (Y) and those by a spectrophotometric method (X) of 169 urine samples in fumigators was expressed by the equation Y = 0.952 + 1.012X (correlation coefficient (r): 0.952). On the other hand, the correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 47 total-blood samples in fumigators was expressed by the equation Y = 1.070 + 0.841 X (correlation coefficient (r): 0.931). The correlation between analytical results by the proposed method (Y) and those by neutron activation analysis (X) of 40 plasma samples in healthy workers was expressed by the equation Y = 0.633 + 0.871 X (correlation coefficient (r): 0.955). The proposed method is much more practical than other methods such as the spectrophotometric method and neutron activation analysis in epidemiological studies, because the proposed method is highly accurate and reproducible over longer periods. The proposed method is useful in biological fluid monitoring of bromide ions.

Pulsatile secretion of prolactin and luteinizing hormone and their synchronous relationship during the human menstrual cycle.

Recent investigations have demonstrated the pulsatile nature of prolactin (PRL) secretion and the synchronous relationship between PRL and LH pulses in normal and hypogonadal women. The present study was designed to confirm this synchrony and to investigate the characteristics of PRL pulses at different stages of the menstrual cycle. Blood samples were obtained at 10-minute intervals, beginning at 10.00 hours, for a duration of 4-7 hours, from women during the follicular (n = 11), preovulatory (n = 2) and luteal (n = 10) phases. Detectable pulses in plasma PRL concentrations were present in almost all subjects during each phase of the cycle. During the total 121-hour blood sampling throughout the 3 phases, 62 PRL pulses and 74 LH pulses were detected and about 80% of the PRL pulses were observed to coincide with LH pulses. The mean (+/- SD) pulse frequency of PRL was significantly lower during the luteal phase (0.28 +/- 0.17 pulses/hour) than during the follicular (0.64 +/- 0.25 pulses/hour) and preovulatory (0.72 +/- 0.16 pulses/hour) phases, while the mean pulse amplitude of PRL was significantly greater during the luteal phase (6.8 +/- 2.3 ng/ml) than during the follicular (3.6 +/- 1.2 ng/ml) and preovulatory (4.1 +/- 1.0 ng/ml) phases. These changes in pulse frequency and amplitude were also observed in LH pulses between the follicular and luteal phases, except at the LH surge, when LH pulse amplitude increased markedly, but that of PRL did not alter. Furthermore, a positive linear correlation between the pulse frequency of PRL and LH (r = 0.74, p less than 0.001) was found throughout the 3 phases of the cycle. These results demonstrate that a marked degree of synchrony between PRL and LH pulses is observed during the menstrual cycle and suggest that the frequency and amplitude of PRL pulses vary from the follicular to luteal phases, except at the LH surge, almost in parallel with those of LH pulses.

Flow cytometric analysis of T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia: correlation with clinical stage.

Several authors have studied the T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia (B-CLL), but previous studies were performed after preceding enrichment procedures, which are known to cause selective losses of certain subpopulations. To correct for this deficiency we used flow cytometric analysis, which enabled us to measure subpopulations directly on total blood samples. We studied T-lymphocyte subsets with OKT monoclonal antibodies in 45 patients with B-CLL. Serum levels of IgG, IgA and IgM were assayed simultaneously and findings were correlated with clinical stage (Rai classification). The absolute number of CD4-positive cells decreased in more advanced Rai stages, while the absolute number of CD8-positive cells increased, resulting in a progressive reduction in CD4/8 ratio. Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups.

The determination of chromium-50 in human blood and its utilization for blood volume measurements

Possible relationships between insufficient blood volume increases during pregnancy and infant mortality could be established with an adequate measurement procedure. An accurate and precise technique for blood volume measurements has been found in the isotope dilution technique using chromium-51 as a label for red blood cells. However, in a study involving pregnant women, only stable isotopes can be used for labeling. Stable chromium-50 can be determined in total blood samples before and after dilution experiments by neutron activation analysis (NAA) or mass spectrometry. However, both techniques may be affected by insufficient sensitivity and contamination problems at the inherently low natural chromium concentrations to be measured in the blood. NAA procedures involving irradiations with highly thermalized neutrons at a fluence rate of 2·1013 n·cm−2·s−1 and low background gamma spectrometry are applied to the analysis of total blood. Natural levels of chromium-50 in human and animal blood have been found to be <0.1 ng/ml; i.e., total chromium levels of <3 ng/ml. Based on the NAA procedure, a new approach to the blood volume measurement via chromium-50 isotope dilution has been developed which utilizes the ratio of the induced activities of chromium-51 to the iron-59 in three blood samples taken from each individual, namely blank, labeled and diluted labeled blood.

An isolated skeletal muscle model suitable for acute ischemia studies

A modified isolated canine gracilis model of acute complete muscle ischemia was developed and then tested metabolically and histologically in 25 animals to assess its validity. In each dog, both gracili were isolated on their major vascular pedicles. One muscle underwent ischemia and reperfusion by placing and removing microvascular clips on the artery and vein. The other gracilis muscle was used as a control. Total muscle blood flow measurements, blood samples, and muscle biopsies were taken every other hour for up to 11 hr after preparation. The fiber-type profile of the gracilis was determined bilaterally using a myosin ATPase stain ( n = 10). The results verified these hypotheses: (1) after surgical preparation, the right and left muscles in the same dog are equivalent metabolically, (2) after a 2-hr stabilization period, gracilis blood flow, oxygen and glucose uptake, lactate release, and tissue glycogen, lactate, phosphocreatine, and ATP levels remain within normal limits and unchanged for the next 9 hr, (3) the surgical isolation of the gracilis muscle on a single vascular pedicle does not result in significant metabolic changes, (4) in this model, a 2-hr ischemia is reversible, but a 7-hr ischemia results in irreversible ischemic injury. As well, fiber-type profile, muscle blood flow, and metabolic parameters can vary significantly among animals supporting the necessity of a contralateral control. Therefore, this modified gracilis muscle model with its contralateral muscle as a control is suitable for acute skeletal muscle ischemia experiments of at least 9-hr duration.

Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.

Influence of removal from occupational lead exposure on blood and saliva lead concentrations

Samples of total blood and unstimulated mixed saliva were obtained from 5 male workers occupationally exposed to lead at various time intervals after removal from their work environment. Initial blood lead concentrations were elevated in all workers and then slowly decreased upon removal. Lead concentrations in saliva fell much more abruptly than those in blood, the saliva half-lives being estimated at 5–7 days. Temporary return to work in 2 workers resulted in relatively marked increases of salivary lead concentrations. These results suggest that salivary lead is closely related to recent lead exposure.

Distribution of chloroquine and its metabolite desethyl-chloroquine in human blood cells and its implication for the quantitative determination of these compounds in serum and plasma

The amount of chloroquine and desethyl-chloroquine was determined in samples of total blood and in blood cell fractions from three normal subjects after one oral dose of 1000 mg of chloroquine diphosphate. About 70–85% of the total whole blood content of choroquine and its metabolite desethyl-chloroquine were recovered in blood cells isolated from whole blood, indicating that these compounds have a high cell/plasma concentration ratio. They were mainly present in thrombocytes and granulocytes. A study of 40 patients taking chloroquine regularly as a treatment for rheumatoid arthritis showed significantly higher concentrations of chloroquine and desethyl-chloroquine in serum than in plasma. The concentration of chloroquine was about two times higher in serum than in plasma and for desethyl-chloroquine the concentration was about four times higher in serum than in plasma. These differences may be explained by a release of chloroquine and desethyl-chloroquine from thrombocytes during the coagulation of blood. The practical implication of the results is that the samples taken for chloroquine determination must be clearly identified as serum or plasma.

Presence of cadmium in the saliva of adult male workers

Samples of mixed saliva were collected from 16 workers exposed to cadmium dusts and fumes and 19 unexposed co-workers. Samples of total blood and plasma were also obtained. Cadmium (Cd) was measured by flameless atomic absorption spectrometry. Cd was found in higher concentrations in saliva than in blood. The concentration of Cd in saliva was markedly elevated in exposed subjects; the difference was less important in blood. Smokers had more Cd in their blood than non-smokers, but this was not the case for saliva. In vitro studies measuring uptake of Cd by slices of rat submaxillary glands indicated that movement of the metal occurs passively.

Dosage des médicaments par spectrophotométrie in situ des chromatogrammes en vue de leur étude pharmacocinétique : I. Sulpiride et autres benzamides, vincamine, naftazone

Quantitative determination of drugs by in situ spectrophotometry of chromatograms for pharmacokinetic studies. I. Sulpiride and other benzamides, vincamine, naftazone. Assays are proposed for sulpiride and other benzamides, vincamine and naftazone in plasma (or blood) and urine with direct UV reflectance spectrophotometry on thin-layer chromatography (TLC) at 293, 280 and 270 nm respectively. Urine samples are applied directly on TLC along with a calibration curve on each plate. Plasma (or total blood) samples are extracted, and an internal standard is added before application; slopes of the obtained calibration curves do not change significantly from plate to plate, thus allowing several determinations on the same plate. The sensitivity is 2 μg in a 1-ml sample (amount applied 30 ng) for sulpiride and related compounds and about the same for vincamine. Naftazone is determined in plasma with simultaneous reflectance and transmittance spectrophotometric measurements at 520 nm on chromatoplates sprayed with lead acetate, the sensitivity reached is 10 ng in a 1-ml sample (amount applied 0.5 ng). For all drugs studied, the proposed techniques are specific, reliable and sensitive enough and can be used to perform pharmacokinetic studies in human or in animal after administration of doses in the therapeutic range.