Real-Time Electron Solvation Induced by Bursts of Laser-Accelerated Protons in Liquid Water.

Understanding the mechanisms of proton energy deposition in matter and subsequent damage formation is fundamental to radiation science. Here we exploit the picosecond (10^{-12} s) resolution of laser-driven accelerators to track ultrafast solvation dynamics for electrons due to proton radiolysis in liquid water (H_{2}O). Comparing these results with modeling that assumes initial conditions similar to those found in photolysis reveals that solvation time due to protons is extended by >20 ps. Supported by magnetohydrodynamic theory this indicates a highly dynamic phase in the immediate aftermath of the proton interaction that is not accounted for in current models.

A thermoluminescence dosimetry system for personal monitoring in Ireland.

In 1993 the decision was taken to replace film badges with thermoluminescence dosemeters (TLDs) as the main form of dosemeter for both whole-body and extremity monitoring at the Dosimetry Service of the Radiological Protection Institute of Ireland (RPII) in Dublin. A review of commercially available automatic TLD systems was carried out to identify the system which best met the RPII's requirements. This paper describes the dosimetry system used, and, in addition, discusses the problems encountered and how these were addressed.

Analysis of whole-body doses received by occupationally exposed workers in Ireland (1996-1999).

The work described in this paper is based on the results of routine whole-body measurements carried out by the Radiological Protection Institute of Ireland Dosimetry Service from 1996 to 1999. Data on the occupational radiation exposures of monitored personnel are examined and have been found to follow the skewed distribution reported by UNSCEAR. The annual average effective dose for each major work practice over the 4 years is given and compared with the UNSCEAR reference value of 1.1 mSv per year for all occupations. Evidence suggests that improvements in procedures and the use of better equipment have resulted in a reduction in the numbers of workers receiving measurable doses.

In vitro and in situ permeability of a 'second generation' hydroxypyridinone oral iron chelator: correlation with physico-chemical properties and oral activity.

PURPOSE: The in vitro and in situ transport of CGP 65015 ((+)-3-hydroxy-1-(2-hydroxyethyl)-2-hydroxyphenyl-methyl-1H-pyridin-4-on e), a novel oral iron chelator, is described. The predictive power of these data in assessing intestinal absorption in man is described. METHODS: Caco-2 epithelial monolayer and in situ rat jejunum perfusion intestinal permeability models were utilized. In vivo iron excretion and preliminary animal pharmacokinetic experiments were described. Ionization constants and octanol/aqueous partition coefficients were measured potentiometrically. Solubilities and intrinsic dissolution rates were determined using standard procedures. RESULTS: Caco-2 cell (Papp approximately 0.25 x 10(-6) cm x s(-1)) and rat jejunum (Pw approximately 0.4) permeabilities of CGP 65015 were determined. The log D(pH 7.4) of CGP 65015 was 0.58 and its aqueous solubility was < 0.5 mg x ml(-1) (pH 3-9). The intrinsic dissolution rate of CGP 65015 in USP simulated intestinal fluid was 0.012 mg x min(-1) x cm(-2). CGP 65015 promotes iron excretion effectively and dose dependently in animals. CONCLUSIONS: Caco-2 and rat intestinal permeabilities predict incomplete oral absorption of CGP 65015 in man. Preliminary rat pharmacokinetics support this. Physico-chemical data are, also, in line and suggest that CGP 65015 may, in addition, be solubility/dissolution rate limited in vivo. Nevertheless, early animal pharmacological data demonstrate that CGP 65015 is a viable oral iron chelator candidate.

Caco-2 cell permeability of a new (hydroxybenzyl)ethylenediamine oral iron chelator: correlation with physicochemical properties and oral activity.

This study describes the transport of CGP 75254A, a novel oral iron chelator, across Caco-2 cells in an attempt to model intestinal epithelial cell permeability in man. CGP 75254A was dosed to the apical side of Caco-2 cell monolayers, together with [14C]mannitol as an internal permeability standard. The apparent permeability (Papp) was calculated from the cumulative appearance of drug in the basolateral fluid with time. The [14C]mannitol Papp indicated that the Caco-2 monolayers remained intact and that the iron chelator was not toxic to the cells. Permeabilities of CGP 75254A were compared with the Caco-2 permeabilities of compounds of known absorption in man. The results predict that absorption of CGP 75254A is likely to be virtually complete at pH values between 5.5 and 7.0. However, at pH 8.0 permeability is predicted as negligible. Cell permeability data are in full accordance with key physicochemical properties of CGP 75254A and suggest that the drug is passively absorbed. The results, which suggest likely quantitative absorption in vivo, are supported by preliminary pharmacological experiments in marmosets.

Light intensity and the oestrous cycle in albino and normally pigmented mice.

The effects of light intensity (15-20 lux & 220-290 lux) on the oestrous cycle of albino and normally pigmented mice were examined. The oestrous cycle of both types of mice was shorter at the lower intensity but the difference was significant only with the black mice. The proportion of albino mice from which embryos were recovered was significantly smaller than the proportion of black mice at 15-20 lux but not at 220-290 lux. No significant differences due to strain or light intensity were found in the number of embryos recovered. We conclude that pigmented mice respond in the same way as albino mice to changes in light intensity within the range normally found in laboratory animal accommodation. That is, increased light intensity prolongs the oestrous cycle and the period of vaginal cornification.

Distribution of pentamidine in patients with AIDS.

We used a bioassay to measure pentamidine concentrations in autopsy specimens from 22 patients with AIDS. Patients received pentamidine isethionate (approximately 4 mg/kg per day) parenterally for Pneumocystis carinii pneumonia; one received monthly prophylaxis. We found that lung levels of 30 micrograms/g were achieved only after the fifth dose; tissue accumulation was usually greater in the liver, kidney, adrenal, and spleen than in the lung; detectable levels were present in some tissues as late as one year after the last dose; and low but detectable levels were present in the brain of six of 17 patients. Two patients had no detectable lung levels after two days of therapy; one had a level of 17.5 micrograms/g after four doses, and two had levels of 30 micrograms/g after five doses. A more rapid and effective method of delivery, such as aerosol, should achieve higher concentrations earlier. Because pentamidine persists in lung tissue over days to weeks, daily administration may not be necessary.

2'-Fluoro-5-iodoarabinosylcytosine, a new potent antiviral agent: efficacy in immunosuppressed individuals with herpes zoster.

2'-Fluoro-5-iodoarabinosylcytosine (FIAC) has potent antiviral activity in vivo against herpes simplex virus types 1 and 2 and cytomegalovirus. For examination of the clinical efficacy of FIAC, a randomized, double-blind study of FIAC versus adenine arabinoside (ara-A) was conducted in 34 immunosuppressed individuals with varicella-zoster virus infections. The median time to the appearance of the last new lesion was shorter in patients who received FIAC relative to those who received ara-A (two versus five days, respectively; P less than .001) FIAC also reduced pain and accelerated initial crusting within 72 hr in a significantly greater proportion of patients when compared with ara-A (P = .004 and P = .0009, respectively). FIAC caused few toxic reactions (mild nausea and transient elevation in activity of serum aspartate aminotransferase). Thus FIAC is therapeutically superior to ara-A for the treatment of varicella-zoster virus infections in immunosuppressed subjects.

Use of a new bioassay to study pentamidine pharmacokinetics.

We developed a sensitive and specific agar-diffusion bioassay for pentamidine by using an amphotericin B-resistant isolate, Candida tropicalis ATCC 28707, as the test organism. We determined levels of pentamidine in serum of rats given intramuscular or intravenous injections and levels in serum, urine, and tissues of humans who had received the drug by slow intravenous infusion. Rats given intravenous pentamidine at a dose of 2 mg/kg had higher serum levels than those given intramuscular injection at a dose of 10 mg/kg; however, the drug was detectable in serum for 4 hr after intramuscular administration. The serum half-life in rats after intravenous injection was 2 min. Humans treated with 4 mg of pentamidine/kg by slow (1-2 hr) intravenous infusion had peak serum concentrations ranging from 0.5 to 3.4 micrograms/ml. The mean half-life of elimination from serum in humans was 17 +/- 4 min (n = 3). In two patients, studied after completion of therapy, urinary excretion rates declined with a half-life of five and nine days. In tissues obtained at autopsy from four patients who had received pentamidine, the drug was present in highest concentration in the spleen and liver, followed by kidneys, adrenals, and lungs.

Continuous high-grade mycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome.

Serial quantitative blood cultures were performed before and during treatment in four patients with the acquired immune deficiency syndrome (AIDS) and Mycobacterium avium-intracellulare bacteremia. Initial colony counts were 350 to 28,000 cfu/ml, the counts declined substantially with treatment in two patients, and they declined modestly with treatment but rose when it was stopped in the other two. In one patient who was studied in detail, most of the circulating organisms were within the leukocytes, colony counts in blood subjected to lytic agents were 1.9- to 5.2-fold higher than in unlysed blood, and there were 10(5) to 10(6) times more organisms per gram in several tissue specimens obtained at autopsy than per milliliter of blood. It is concluded that continuous high-grade bacteremia is common in patients with AIDS and severe M. avium-intracellulare infections and that serial quantitative blood cultures provide a potential means for studying treatment in these patients.

L(2) Cohomology of the Bergman metric.

The L(2) cohomology of the Bergman metric is infinite dimensional in the middle degree and vanishes for all other degrees. Asymptotic expansions are given for the Schwartz kernels of the corresponding projections onto harmonic forms.

Geometry and analysis of Shimizu L-functions.

The values of 0 of Shimizu L-functions are realized as the signature defects of framed manifolds. This settles a conjecture of Hirzebruch [Hirzebruch, F. (1973) Enseign. Math. 19, 183-281] affirmatively. The proof employs the spectral theory of elliptic operators.

Oxygen consumption, activity and body fat in normal and hairless mice.

The oxygen consumption spontaneous activity of A2G (hr/+), A2G (hr/hr) and NMRI mice in groups of 2, 3, or 5 were measured, and body fat content was also determined. Average rates of oxygen consumption were found to be lowest in the A2G (hr/+) and highest in the A2G (hr/hr) mice, and conversely for the proportion of total body fat. There was no difference in activity of A2G (hr/+) and A2G (hr/hr), but the NMRI mice were more active.

Survey of the numbers and species of amphibia used in the United Kingdom in 1977.

This survey suggests that about 115 000 amphibia, of which more than half were Rana temporaria, were supplied for use in teaching and research in the UK during 1977. As only 27 000 were recorded as being used by universities, polytechnics and research institutes, probably mostly for teaching, it must be assumed that the majority are used for teaching purposes in schools. There has been an increase in the proportion of amphibia supplied by Recognised Suppliers, and also in that being 'purpose-bred' although breeding in the laboratory is still restricted to Xenopus laevis and Ambystoma mexicanum. Probable cost appears to be a deterent to the use of purpose-bred amphibia. A large number of respondents had encountered problems with using amphibia, mainly losses due to 'red leg' and arrival from the supplier in poor condition, probably interrelated.

Anaemia and veal calf production.

Calves have been raised for veal on liquid diets containing different amounts of iron. A concentration of 25-30 mg soluble iron/kg dietary dry matter provided sufficient haemaglobin for normal appetite, growth and oxygen transport, and also produced carcases light coloured enough for the veal trade. When anaemia was induced in calves or sheep the first measurable response from the animals was a fall in appetite which provided a more sensitive indicator than more complicated physiological or biochemical measurements.