Environmental monitoring through use of silica-based TLD.

The sensitivity of a novel silica-based fibre-form thermoluminescence dosimeter was tested off-site of a rare-earths processing plant, investigating the potential for obtaining baseline measurements of naturally occurring radioactive materials. The dosimeter, a Ge-doped collapsed photonic crystal fibre (PCFc) co-doped with B, was calibrated against commercially available thermoluminescent dosimetry (TLD) (TLD-200 and TLD-100) using a bremsstrahlung (tube-based) x-ray source. Eight sampling sites within 1 to 20 km of the perimeter of the rare-earth facility were identified, the TLDs (silica- as well as TLD-200 and TLD-100) in each case being buried within the soil at fixed depth, allowing measurements to be obtained, in this case for protracted periods of exposure of between two to eight months. The values of the dose were then compared against values projected on the basis of radioactivity measurements of the associated soils, obtained via high-purity germanium gamma-ray spectrometry. Accord was found in relative terms between the TL evaluations at each site and the associated spectroscopic results. Thus said, in absolute terms, the TL evaluated doses were typically less than those derived from gamma-ray spectroscopy, by ∼50% in the case of PCFc-Ge. Gamma spectrometry analysis typically provided an upper limit to the projected dose, and the Marinelli beaker contents were formed from sieving to provide a homogenous well-packed medium. However, with the radioactivity per unit mass typically greater for smaller particles, with preferential adsorption on the surface and the surface area per unit volume increasing with decrease in radius, this made for an elevated dose estimate. Prevailing concentrations of key naturally occurring radionuclides in soil, 226Ra, 232Th and 40K, were also determined, together with radiological dose evaluation. To date, the area under investigation, although including a rare-earth processing facility, gives no cause for concern from radiological impact. The current study reveals the suitability of the optical fibre based micro-dosimeter for all-weather monitoring of low-level environmental radioactivity.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta-analysis.

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

Levels of APE1 Repair Gene and CLEC4M in Lung Cancer Patients Receiving Cisplatin Chemotherapy.

This study aimed to detect the levels of apurinic/apyrimidinic endonuclease 1 (APE1) gene expression and C-type lectin domain family 4 member M (CLEC4M) and their association with cisplatin chemotherapy in lung cancer patients. Overall, 105 individuals who attended the Al-Amal National Hospital for Cancer Management, Baghdad, Iraq, were enrolled in the study and divided into three equal groups. The groups included the patients newly diagnosed with lung cancer, cancer patients who received cisplatin, and the healthy control group. All study groups were subjected to the sampling of the venous blood for molecular analysis by real-time polymerase chain reaction (RT-PCR) to detect the APE1 gene and enzyme-linked immunosorbent assay (ELISA) for serological testing to measure the concentration of CLEC4M protein. Significantly, the values of both cancer groups were higher than those reported in the control group. The relative index revealed a significant difference in the mean fold change level of APE1 in the newly diagnosed group (3 fold) and cisplatin therapy patients group (2 fold), compared to the control group (P=0.005). No significant differences were detected between the two cancer groups in terms of fold change mean of expression, demographic characteristics, and cancer histological type. Regarding human CLEC4M protein level, cases receiving cisplatin (139.2±25.9) and newly diagnosed patients (331.0±38.1) had a highly significant difference with the control group (100.3±47.5, P<0.001). There was no significant difference between the concentration level of CLEC4M and all parameters in demographic characteristics and cancer histological type. This was the first study to demonstrate that higher expression levels of new APE1, CLEC4M, and glutathione, especially after chemotherapy, are beneficial as diagnostic and prognostic markers for resistance to platinum chemotherapy in Iraqi lung cancer patients.

Thermoluminescence Response of Ge-Doped Cylindrical-, Flat- and Photonic Crystal Silica-Fibres to Electron and Photon Radiation.

Study has been made of the thermoluminescence (TL) response of silica-based Ge-doped cylindrical, flat and photonic crystal fibres (referred to herein as PCF-collapsed) to electron (6, 12 and 20 MeV) and photon (6, 10 MV) irradiation and 1.25 MeV γ-rays, for doses from 0.1 Gy to 100 Gy. The electron and photon irradiations were delivered through use of a Varian Model 2100C linear accelerator located at the University of Malaya Medical Centre and γ-rays delivered from a 60Co irradiator located at the Secondary Standard Dosimetry Laboratory (SSDL), Malaysian Nuclear Agency. Tailor-made to be of various dimensions and dopant concentrations (6-10% Ge), the fibres were observed to provide TL yield linear with radiation dose, reproducibility being within 1-5%, with insensitivity to energy and angular variation. The sensitivity dependency of both detectors with respect to field size follows the dependency of the output factors. For flat fibres exposed to 6 MV X-rays, the 6% Ge-doped fibre provided the greatest TL yield while PCF-collapsed showed a response 2.4 times greater than that of the 6% Ge-doped flat fibres. The response of cylindrical fibres increased with core size. The fibres offer uniform response, high spatial resolution and sensitivity, providing the basis of promising TL systems for radiotherapy applications.

Measurement of radioactivity and heavy metal levels in edible vegetables and their impact on Kuala Selangor communities of Peninsular Malaysia.

Vegetable is an essential daily diet item for the people of Malaysia. This work addressed the radiation and heavy metal exposure scenarios through the consumption of vegetables. Kuala Selangor is located in Sungai Selangor estuary in the west coast of Peninsular Malaysia, which is susceptible to pollution load due to the presence of large-scale industrial and human activities. Radioactivity and heavy metals level in human diet is of particular concern for the assessment of possible radiological and chemical hazards to human health. Therefore, a comprehensive study was carried out to determine the radioactivity levels ((226)Ra, (228)Ra and (40)K) and heavy metal concentrations (Cr, As, Cd, Mn, Mg, Al, Sr, Rb, Sb, Ba, Hg, Fe, Ni, Zn, Cu, Bi and Pb) in 10 varieties of vegetable collected from different farmlands in Kuala Selangor region. The committed doses for (226)Ra, (228)Ra and (40)K due to consumption of vegetables were found 16.6±1.3, 23.6±1.7 and 58±5 µSv y(-1), respectively, with a total of 98±8 µSv y(-1). This dose imposes no significant threat to human health. The estimated cancer risk shows that probability of increase in cancer risk from daily intake of vegetables is only a minor fraction of International Commission on Radiological Protection values. The concentrations of heavy metal were below the daily intake recommended by the international organisations.

Assessment of Radiation and Heavy Metals Risk due to the Dietary Intake of Marine Fishes (Rastrelliger kanagurta) from the Straits of Malacca.

The environment of the Straits of Malacca receives pollution as a result of various industrial and anthropogenic sources, making systematic studies crucial in determining the prevailing water quality. Present study concerns concentrations of natural radionuclides and heavy metals in marine fish (Rastrelliger kanagurta) collected from the Straits of Malacca, since aquatic stock form an important source of the daily diet of the surrounding populace. Assessment was made of the concentrations of key indicator radionuclides (226Ra, 232Th, 40K) and heavy metals (As, Mn, Fe, Cr, Ni, Zn, Cu, Co, Sr, Al, Hg and Pb) together with various radiation indices linked to the consumption of seafish. The annual effective dose for all detected radionuclides for all study locations has been found to be within UNSCEAR acceptable limits as has the associated life-time cancer risk. The overall contamination of the sampled fish from heavy metals was also found to be within limits of tolerance.

Natural radioactivity and effective dose due to the bottom sea and estuaries marine animals in the coastal waters around Peninsular Malaysia.

Malaysia is among the countries with the highest fish consumption in the world and relies on seafood as a main source of animal protein. Thus, the radioactivity in the mostly consumed marine animals such as fishes, crustaceans and molluscs collected from the coastal waters around Peninsular Malaysia has been determined to monitor the level of human exposure by natural radiation via seafood consumption. The mean activity concentrations of naturally occurring radionuclides (226)Ra ((238)U), (228)Ra ((232)Th) and (40)K ranged from 0.67 ± 0.19 Bq kg(-1) (Perna viridis) to 1.20 ± 0.70 Bq kg(-1) (Rastrelliger), from 0.19 ± 0.17 Bq kg(-1) (Teuthida) to 0.82 ± 0.67 Bq kg(-1) (Caridea) and from 34 ± 13 Bq kg(-1) (Caridea) to 48 ± 24 Bq kg(-1) (Teuthida), respectively. The mean annual committed effective dose due to the individual radionuclides shows an order of (228)Ra > (226)Ra > (40)K in all marine samples. The obtained doses are less than the global internal dose of 290 µSv y(-1) set by the United Nations Scientific Committee on the Effects of Atomic Radiation, discarding any significant radiological risks to the populace of Peninsular Malaysia.

Thermoluminescence characteristics of Ge-doped optical fibers with different dimensions for radiation dosimetry.

Important thermoluminescence (TL) properties of five (5) different core sizes Ge-doped optical fibers have been studied to develop new TL material with better response. These are drawn from same preform applying different speed and tension during drawing phase to produce Ge-doped optical fibers with five (5) different core sizes. The results of the investigations are also compared with most commonly used standard TLD-100 chips (LiF:Mg,Ti) and commercial multimode Ge-doped optical fiber (Yangtze Optical Fiber, China). Scanning Electron Microscope (SEM) and EDX analysis of the fibers are also performed to map Ge distribution across the deposited region. Standard Gamma radiation source in Secondary Standard Dosimetry Lab (SSDL) was used for irradiation covering dose range from 1Gy to 10Gy. The essential dosimetric parameters that have been studied are TL linearity, reproducibility and fading. Prior to irradiation all samples ∼0.5cm length are annealed at temperature of 400°C for 1h period to standardize their sensitivities and background. Standard TLD-100 chips are also annealed for 1h at 400°C and subsequently 2h at 100°C to yield the highest sensitivity. TL responses of these fibers show linearity over a wide gamma radiation dose that is an important property for radiation dosimetry. Among all fibers used in this study, 100µm core diameter fiber provides highest response that is 2.6 times than that of smallest core (20µm core) optical fiber. These fiber-samples demonstrate better response than commercial multi-mode optical fiber and also provide low degree of fading about 20% over a period of fifteen days for gamma radiation. Effective atomic number (Zeff) is found in the range (13.25-13.69) which is higher than soft tissue (7.5) however within the range of human-bone (11.6-13.8). All the fibers can also be re-used several times as a detector after annealing. TL properties of the Ge-doped optical fibers indicate promising applications in ionizing radiation dosimetry.

Management of severe ovarian hyperstimulation syndrome by ascitic fluid aspiration and intensive intravenous fluid therapy.

OBJECTIVE: To assess the value of intensive intravenous (IV) fluid therapy and ascitic fluid aspiration in the management of severe ovarian hyperstimulation syndrome. METHODS: Forty-two women with severe ovarian hyperstimulation syndrome were treated by ultrasonically guided transvaginal aspiration of ascitic fluid and IV fluid infusion. Ten women with the same condition treated conservatively constituted a comparison group. The main outcome measures included percentage change in hematocrit, creatinine clearance, and urine output before and after aspiration. The duration of hospital stay was compared between the groups. RESULTS: Marked improvement of symptoms and general condition followed soon after aspiration. Hematocrit readings decreased by 22%, creatinine clearance increased by 79.3%, and urine output increased by 220.7%. The average volume of aspirated fluid was 3900 mL. The average duration of hospital stay was 3.8 days in the treated women. In the comparison group, severe symptoms and electrolyte imbalance continued for an average of 9 days, and the average hospital stay was 11 days. CONCLUSION: Intensive IV fluid therapy and transvaginal aspiration of ascitic fluid are safe and effective in improving symptoms, preventing complications, and shortening the hospital stay in severe ovarian hyperstimulation syndrome.

Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters.

OBJECTIVE: To compare the results of IVF and intracytoplasmic sperm injection (ICSI) in tubal factor infertility with normal semen parameters. DESIGN: A prospective randomized study. SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: One hundred sixteen patients infertile due to tubal factor were divided randomly into two groups. Group A(n = 58) was treated with IVF and group B(m = 58) was treated with ICSI. INTERVENTION: In vitro fertilization and ICSI. MAIN OUTCOME MEASURE: Pregnancy rate. RESULTS: In group A, 736 oocytes were retrieved and normal (two pronuclear [2pN] fertilization occurred in 477 oocytes (64.8%). In group B, 748 oocytes were retrieved, 572 metaphase II oocytes were injected, and 2PN fertilization occurred in 400 oocytes (70% per injected oocyte and 53.5% per retrieved oocyte). Clinical pregnancy was diagnosed in 18 patients in group A (31%) and 19 patients in group B (32.8%). There was no significant difference in the pregnancy rate between the two groups. The fertilization rate per retrieved oocytes was significantly higher in group A. CONCLUSIONS: Intracytoplasmic sperm injection does not offer a higher pregnancy rate as compared with IVF in the treatment of tubal factor infertility with normal semen.

The effect of sperm parameters on the outcome of intracytoplasmic sperm injection.

OBJECTIVE: To investigate the influence of sperm parameters on the fertilization and pregnancy rates in intracytoplasmic sperm injection (ICSI). DESIGN: A retrospective analysis of 130 cycles of ICSI performed for the treatment of male factor infertility. SETTING: The Egyptian IVF-ET Center. PARTICIPANTS: One hundred thirty couples with the diagnosis of male factor infertility or with previous failed fertilization in conventional IVF or subzonal sperm injection. INTERVENTION: Ovum pick-up and ICSI. MAIN OUTCOME MEASURE: Fertilization and pregnancy rates in relation to different semen parameters. RESULTS: A total of 1,433 oocytes were retrieved and 1,071 metaphase II oocytes were injected. Normal fertilization occurred in 620 oocytes (58%). Embryo transfer was done for 128 (98.5%) patients, and a total of 46 (35%) clinical pregnancies were achieved. There was no statistically significant difference in the fertilization or pregnancy rates between patients who had previously failed fertilization in conventional IVF, patients with subfertile semen, patients with semen between 1 and 10 x 10(6)/mL, and patients with semen < 1 x 10(6)/mL. There was also no significant difference in the fertilization and pregnancy rates between patients with < 95% or > 95% teratozoospermia. CONCLUSION: In ICSI, the fertilization and pregnancy rates are not affected by different semen parameters as long as morphologically well-shaped live sperms could be used for the injection.

Oocyte quality in patients with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To study the oocyte quality in patients with ovarian hyperstimulation syndrome (OHSS). DESIGN: Retrospective study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Forty-two patients who developed severe OHSS (group A) were studied for the mean number of oocytes retrieved, percentage of high-quality oocytes, embryo quality, and fertilization, implantation, and pregnancy rates; these patients were compared with an age-matched control group who did not develop OHSS (group B; n = 183) after superstimulation for IVF or intracytoplasmic sperm injection. INTERVENTION(S): In vitro fertilization and ICSI. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates. RESULT(S): In group A, the mean number of oocytes retrieved was significantly higher, whereas the percentage of high-quality oocytes and the fertilization rate were significantly lower than that in group B. There were no statistically significant differences in the quality of embryos transferred or the implantation or pregnancy rate between the groups. The percentage of high-quality oocytes and the fertilization rate were significantly lower in patients with polycystic ovaries (PCO) in both groups. CONCLUSION(S): The inferior quality and maturity of oocytes in OHSS reduced the fertilization rate but did not affect the quality or the number of embryos transferred or the pregnancy rate. The effect on oocyte quality could be due to the prevalence of PCO in this group of patients.

Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm.

OBJECTIVE: To compare the fertilization rates and pregnancy rates (PRs) in intracytoplasmic sperm injection (ICSI) using sperm from ejaculates of normal and abnormal semen, epididymal sperm, and testicular sperm of obstructive and nonobstructive azoospermic patients. DESIGN: Retrospective study. SETTING: The Egyptian IVF-ET Center. PATIENT(S): Three hundred fifty patients underwent 366 ICSI cycles. INTERVENTION(S): ICSI, epididymal sperm aspiration, and testicular biopsy. MAIN OUTCOME MEASURE(S): Fertilization rates and PRs. RESULT(S): Patients were divided into five groups according to the quality and source of sperm. Patients in group 1 underwent 102 cycles of ICSI using ejaculated abnormal semen, group 2 underwent 44 cycles using epididymal sperm, group 3 underwent 82 cycles using testicular sperm from obstructive azoospermia, group 4 underwent 80 cycles using testicular sperm from nonobstructive azoospermia, and group 5 underwent 58 cycles using normal semen. There was no significant difference in the fertilization rates and PRs among groups 1, 2, and 3. In group 4, the fertilization rate and PR were significantly lower than in all other groups. In group 5, the fertilization rate was significantly higher than in all other groups. CONCLUSION(S): The fertilizing ability of sperm in ICSI is highest with normal semen and lowest with sperm extracted from a testicular biopsy in nonobstructive azoospermia. There was no significant difference in fertilization rates and PRs between ejaculated sperm of different parameters and surgically retrieved sperm in obstructive azoospermia.

Recombinant follicle-stimulating hormone in the treatment of patients with history of severe ovarian hyperstimulation syndrome.

OBJECTIVE: To compare the low-dose recombinant FSH and hMG protocols in treatment of patients with history of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: A prospective study on 22 patients with history of severe OHSS. Group A (n = 14) was treated with low-dose recombinant FSH 40 cycles and group B (n = 8) was treated with low-dose hMG in 26 cycles. SETTING: The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S): Twenty-two patients with a history of severe OHSS. INTERVENTION(S): Ovulation induction. MAIN OUTCOME MEASURE(S): Estradiol, number of follicles, number of hMG ampules, pregnancy rate (PR), and the development of OHSS. RESULT(S): The cancellation rate, mean E2 level on day of hCG, mean number of days of stimulation, and the mean number of ampules per cycle were 10%, 523 +/- 166 pg/mL (conversion factor to SI unit, 3.671), 17.8 +/- 5.4, and 19 +/- 6.5 in group A and 19.2%, 554 +/- 152 pg/mL, 14.6 +/- 2.5, and 16.1 +/- 3.6 in group B, respectively. Treatment resulted in eight pregnancies (20% per cycle) and two abortions (25%) in group A. In group B, four pregnancies resulted (15.4% per cycle) and two patients aborted (50%). No cases of OHSS developed in both groups. There were no significant differences in all parameters between the two groups. CONCLUSION(S): Recombinant FSH low-dose protocol proved to be as effective as low-dose hMG in producing reasonable ovulation and PRS in polycystic ovary syndrome patients with a history of severe OHSS and the protocol was safe concerning the risk of development of OHSS.

Multifetal pregnancy reduction: modification of the technique and analysis of the outcome.

OBJECTIVE: To modify the technique of multifetal pregnancy reduction and to study the outcome of reduced twins in comparison with nonreduced twins and high-order multiple gestations. DESIGN: Prospective controlled study. SETTING: The Egyptian IVF-ET Center, Cairo. PATIENT(S): Seventy-five patients with high-order multiple pregnancies resulting from assisted reproduction. Controls were 40 nonreduced twin pregnancies and 22 high-order multiple gestations. INTERVENTION(S): Transvaginal ultrasonically guided multifetal pregnancy reduction was performed. The first 30 cases were done using KCl as a cardiotoxic agent. The modified technique was used for the last 45 cases at an earlier gestational age (approximately 7 weeks) by eliminating the use of KCI and by aspirating the embryonic parts. MAIN OUTCOME MEASURE(S): Miscarriage rate, gestational age at delivery, birth weight, and pregnancy complications. RESULT(S): Using the modified technique, the miscarriage rate was 8.8% and 41 patients delivered between 32 and 39 weeks of gestation (mean+/-SD, 36.9+/-2.45 weeks). The mean (+/-SD) birth weight was 2,450.51+/-235.44 g. The miscarriage rate, fetal wastage rate, mean gestational age, and mean birth weight were similar in reduced and nonreduced twins and were significantly better than in nonreduced triplets and quadruplets. CONCLUSION(S): The modified technique of multifetal pregnancy reduction significantly improved outcomes, which were similar to those of nonreduced twins resulting from assisted reproduction and significantly better than those of nonreduced triplets and quadruplets.

Rationale for apparent differences in pharmacokinetic aspects of model compounds determined from blood level data and urinary excretion data in rats.

Results of studies carried out in rats for model compounds, D-(-) mandelic acid, benzoylformic acid, and some of their para-alkylated homologs, showed that their biological half-lives determined from the elimination phase of urinary excretion data were longer than those determined from the elimination phase of blood level data. With compounds that followed multicompartment open models, the initial distributive phase (alpha-phase) noted from the blood level data was not detected from the urinary excretion data. Based on the analysis of half-life data obtained in the absence and presence of DL-tropic acid (a competitive renal tubular secretion inhibitor of these compounds), it is proposed that, besides the shortness of the alpha-phase period, the factor accounting for these compounds is their retention and/or detention in the renal tubular membranes during their tubular secretion. Furthermore, it is proposed that the renal tubular membranes do not constitute a part of the central or peripheral compartment. Examples are cited to show that, where studies are reported for the same drugs in the same human subjects in the same laboratory, drugs usually exhibit longer biological half-lives when urinary excretion data rather than blood level data are used.

Utilization of model compounds to evaluate effects of slight chemical modifications on their distribution. Pharmacokinetic parameters in rats and mechanisms inferred for their transmembrane transport.

The pharmacokinetics of each of the model compounds benzoylformic acid (I), p-methylbenzoylformic acid (II), p-ethylbenzoylformic acid (III), D-(-)-mandelic acid (IV), D-(-)-p-methylmandelic acid (V), D-(-)-p-ethylmandelic acid (VI), and D-(-)-p-isopropylmandelic acid (VII) were studied in rats to determine the influence of slight chemical modifications of the compounds on their distribution pharmacokinetic parameters in rats. The effects of the specific chemical modifications considered were those of the less than CHOH group of IV against the less than C=0 group of I, the para-alkylation of I and IV, and the branched alkyl group (isopropyl) against the straight chain alkyl groups of the homologs of IV. While the disappearance of I from the blood was describable by the three-compartment open model, that of IV was describable by the two-compartment open model. The apparent volume of distribution of the central compartment (V1) for IV was smaller than that for I, but the volume of the peripheral compartment (V2) for IV was greater than that (V2 + V3) for I. The disappearance of V, VI, and VII from the blood was also describable by the two-compartment open model, but the apparent V1 and V2 for these compounds were lower than those for the parent compound, IV. However, the disappearance of II and II from the blood was describable by a one-compartment open model. Evaluation of the appropriate distribution pharmacokinetic parameters suggested that the peripheral compartment for the anions of these compounds consisted of moderately perfused tissues and that the transmembrane transport of these organic anions between the central and peripheral compartments occurs by diffusion mainly through the aqueous membrane pores, which are lined with polar portions of membrane proteins and/or phospholipids. The possible increased hydrophobic bonding between the alkyl groups of these compounds and the hydrophobic groups of the proteins and/or phospholipids of the membrane pores is implicated to decrease the distribution of the para-alkylated homologs into the peripheral compartments and, consequently, diminish the volumes of their peripheral compartments. The heteroporosity of the membranes of the tissues of the central compartment is proposed as the reason for the diminished volume of the central compartment for V and VI as compared to that of IV or VII.

Mechanistic evaluation of modifications of distribution. Pharmacokinetic parameters of model organic anions in presence of a model renal tubular secretion inhibitor in rats.

The effects of DL-tropic acid (VIII) on the distribution pharmacokinetic parameters of the model compounds benzoylformic acid (I), p-methylbenzoylformic acid (II), p-ethylbenzoylformic acid (III), D-(-)-mandelic acid (IV), D-(-)-p-methyl-mandelic acid (V), D-(-)-p-ethylmandelic acid (VI), and D-(-)-p-isopropylmandelic acid (VII) were studied in rats. Since VIII is a competitive inhibitor of renal tubular secretion of I-VII and since all of these compounds (I-VIII) are negligibly bound to plasma proteins and are neither metabolized nor reabsorbed from the renal tubules, they were considered as model compounds. Therefore, changes observed in the values of the distribution pharmacokinetic parameters of I-VII were attributed to the influence of VIII on the transmembrane transport of the compounds between body compartments in rats. The decrease in the apparent volumes of the central compartments for I, IV, and VII, the increase in the apparent volumes of the peripheral compartments for IV-VII, the absence of change in the volumes of the central or peripheral compartments for the other compounds, and the increase in the ratios of the rate constants of the transfer of compounds from one compartment into another for I and IV-VII were explained in terms of the "aqueous pore" mechanism for the transmembrane transport of the anions of the compounds as well as the heteroporosity of the tissue membranes.

Fluorocarbon aerosol propellants XII: Correlation of blood level of trichloromonofluoromethane to cardiovascular and respiratory responses in anesthetized dogs.

Anesthetized mongrel dogs were exposed to various concentrations of trichloromonofluoromethane. Before, during, and after the inhalation, arterial and venous blood samples were obtained for fluorocarbon analysis. After the cessation of fluorocarbon inhalation, a multiexponential decline for the blood was observed. This finding was similar to that of previous study in which the fluorocarbon was administered intravenously to unanesthetized dogs. The half-life calculated from the terminal phase was about 280 min, and the pseudodistribution equilibrium was reached about 100 min after dosing. Study of the relationship between blood fluorocarbon levels and effects on the respiration rate and arterial blood pressure indicates that the sites of these pharmacological activities are located in the blood or central compartment rather than in the peripheral compartment. The effect on the heart rate appears to be quite instantaneous after inhalation. These results might shed some light on the fast effect of the fluorocarbon propellants, which caused sudden deaths after inhalation of a large quantity.