Germination response of Phalaris paradoxa L. seed to different light qualities

The influence of different light regimes on the germination of Australian and English populations of Phalaris paradoxa L. (awned canary-grass) seed was investigated to determine the impact of changing tillage practices on weed infestation. Seeds of all biotypes were highly viable, but differed in levels of innate dormancy (26-99%). In one experiment seed from a single Australian biotype, either enclosed in the spikelet glumes or having the spikelet glumes removed, were exposed to nine light treatments. Germination was stimulated by red and white light, but was inhibited by far-red light. Time to 50%, germination was less for seed enclosed in the spikelet glumes than for naked caryopses, although the final percentage of seed germinating when still enclosed in the spikelet glumes was significantly lower than for naked caryopses. In another experiment, six Australian and English biotypes with varying dormancy characteristics were exposed to eight light treatments. Red light did not stimulate germination in the deeply dormant biotype, however stimulated all other biotypes. Germination in darkness was below 20% in all biotypes except for one where germination was 51%. To overcome dormancy seeds were imbibed and placed in darkness at 16degreesC for either 7 or 14 days prior to exposure to red or white light for a single 15-min period. Dormancy in all biotypes was overcome indicating that a period of burial may decrease the dormancy level and increase seed sensitivity to light. This increased light sensitivity suggests that exposure to light during tillage may stimulate germination in P. paradoxa seed.

Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation

The aim of this review is to analyse critically the recent literature on the clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplant recipients. Dosage and target concentration recommendations for tacrolimus vary from centre to centre, and large pharmacokinetic variability makes it difficult to predict what concentration will be achieved with a particular dose or dosage change. Therapeutic ranges have not been based on statistical approaches. The majority of pharmacokinetic studies have involved intense blood sampling in small homogeneous groups in the immediate post-transplant period. Most have used nonspecific immunoassays and provide little information on pharmacokinetic variability. Demographic investigations seeking correlations between pharmacokinetic parameters and patient factors have generally looked at one covariate at a time and have involved small patient numbers. Factors reported to influence the pharmacokinetics of tacrolimus include the patient group studied, hepatic dysfunction, hepatitis C status, time after transplantation, patient age, donor liver characteristics, recipient race, haematocrit and albumin concentrations, diurnal rhythm, food administration, corticosteroid dosage, diarrhoea and cytochrome P450 (CYP) isoenzyme and P-glycoprotein expression. Population analyses are adding to our understanding of the pharmacokinetics of tacrolimus, but such investigations are still in their infancy. A significant proportion of model variability remains unexplained. Population modelling and Bayesian forecasting may be improved if CYP isoenzymes and/or P-glycoprotein expression could be considered as covariates. Reports have been conflicting as to whether low tacrolimus trough concentrations are related to rejection. Several studies have demonstrated a correlation between high trough concentrations and toxicity, particularly nephrotoxicity. The best predictor of pharmacological effect may be drug concentrations in the transplanted organ itself. Researchers have started to question current reliance on trough measurement during therapeutic drug monitoring, with instances of toxicity and rejection occurring when trough concentrations are within 'acceptable' ranges. The correlation between blood concentration and drug exposure can be improved by use of non-trough timepoints. However, controversy exists as to whether this will provide any great benefit, given the added complexity in monitoring. Investigators are now attempting to quantify the pharmacological effects of tacrolimus on immune cells through assays that measure in vivo calcineurin inhibition and markers of immuno suppression such as cytokine concentration. To date, no studies have correlated pharmacodynamic marker assay results with immunosuppressive efficacy, as determined by allograft outcome, or investigated the relationship between calcineurin inhibition and drug adverse effects. Little is known about the magnitude of the pharmacodynamic variability of tacrolimus.

Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units

Objective. To determine the population incidence and outcome of severe sepsis occurring in adult patients treated in Australian and New Zealand intensive care units (ICUs), and compare with recent retrospective estimates from the USA and UK. Design. Inception cohort study. Setting. Twenty-three closed multi-disciplinary ICUs of 21 hospitals (16 tertiary and 5 university affiliated) in Australia and New Zealand. Patients. A total of 5878 consecutive ICU admission episodes. Measurements and results. Main outcome measures were population-based incidence of severe sepsis, mortality at ICU discharge, mortality at 28 days after onset of severe sepsis, and mortality at hospital discharge. A total of 691 patients, 11.8 (95% confidence intervals 10.9-12.6) per 100 ICU admissions, were diagnosed with 752 episodes of severe sepsis. Site of infection was pulmonary in 50.3% of episodes and abdominal in 19.3% of episodes. The calculated incidence of severe sepsis in adults treated in Australian and New Zealand ICUs is 0.77 (0.76-0.79) per 1000 of population. 26.5% of patients with severe sepsis died in ICU, 32.4% died within 28 days of the diagnosis of severe sepsis and 37.5% died in hospital. Conclusion. In this prospective study, 11.8 patients per 100 ICU admissions were diagnosed with severe sepsis and the calculated annual incidence of severe sepsis in adult patients treated in Australian and New Zealand ICUs is 0.77 per 1000 of population. This figure for the population incidence falls in the lower range of recent estimates from retrospective studies in the U.S. and the U.K.

A randomised controlled study of the efficacy of hypromellose and Lacri-Lube combination versus polyethylene/Cling wrap to prevent corneal epithelial breakdown in the semiconscious intensive care patient

Objective. To compare the efficacy of two forms of eye care (hypromellose and Lacri-Lube combination vs polyethylene/Cling wrap covers) for intensive care patients. Design. Randomised-controlled trial. Setting. University affiliated, tertiary referral hospital. Patients and participants. One hundred ten patients with a reduced or absent blink reflex were followed through until they regained consciousness, were discharged from the facility during study enrolment, died or developed a positive corneal ulcer or eye infection. Interventions. All patients received standard eye cleansing every 2 h. In addition to this, group one (n=60) received a treatment combining hypromellose drops and Lacri-Lube (HL) to each eye every 2 h. Group two (n=50) had polyethylene covers only placed over the eye to create a moisture chamber. Measurements and results. Corneal ulceration was determined using corneal fluorescein stains and mobile slit lamp evaluation, performed daily. No patients had corneal ulceration in the polyethylene cover group, but 4 patients had corneal ulceration in the HL group. Conclusions. Polyethylene covers are as effective as HL in reducing the incidence of corneal damage in intensive care patients.

The effect of adsorption, filter material and point of dilution on antibiotic elimination by haemofiltration - An in vitro study of levofloxacin

We studied an in vitro model of continuous venous-venous haemofiltration (CVVH), into which levofloxacin 100 mg was infused, to determine levofloxacin adsorption and to determine the effect of filter material and point of dilution (pre- or post-filter) on sieving coefficient. Mean (standard deviation; S.D.) adsorption was 18.7 (5.3) mg for the polyamide filter and 40.2 (2.0) mg for the polyacrylonitrile (PAN) filter (P < 0.001). Post-dilution resulted in a minor, but statistically significant, decrease in sieving coefficient (pre-dilution 0.96 (S.D. 0.10), post-dilution 0.88 (S.D. 0.11) with the PAN filter. These data indicate that the variability in published values for levofloxacin sieving coefficient are not due to variation in point of dilution or membrane type (PAN or polyamide). Significant adsorption of levofloxacin onto PAN filters occurs. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Effect of clarithromycin on nuclear factor-kappa B and transforming growth factor-beta in chronic rhinosinusitis

Objectives: Long-term, low-dose macrolide therapy is effective in the treatment of chronic rhinosinusitis. It is believed that macrolide antibiotics produce this benefit through an anti-inflammatory effect. In this study, the effect of clarithromycin treatment on the expression of transforming growth factor (TGF)-beta and the key pro-inflammatory nuclear transcription factor, NF-kappaB, was examined in vitro and in vivo. Study Design and Methods: In vitro: nasal mucosa was obtained from 10 patients with chronic sinusitis and was cultured for 24 hours in the presence of clarithromycin or control. Cellular expression of TGF-beta and NF-kappaB was determined by immunohistochemistry. In vivo: 10 patients with chronic rhinosinusitis were treated for 3 months with clarithromycin. Nasal mucosal biopsies were taken pre- and posttreatment. Cellular expression of TGF-beta and NF-kappaB was again determined by immunohistochemistry. Results: Clarithromycin, when applied to nasal biopsies in vitro, reduced cellular expression of TGF-beta and NF-kappaB. Nasal biopsies taken before and after clarithromycin treatment showed no differences in cellular expression of NF-kappaB or TGF-beta. Conclusion: Clarithromycin can reduce cellular expression of TGF-beta and NF-kappaB when applied in vitro, but its action during clinical therapy is less clear. Clarithromycin is capable of inhibiting pro-inflammatory cytokines in vitro, and reductions of TGF-beta and NF-kappaB may represent additional mechanisms by which macrolides reduce inflammation in chronic airway disease. Discrepancies between the actions of clarithromycin on nasal biopsies in vitro and after clinical therapy warrant further investigation.

Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis

Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), iron-regulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Iregl expression. In cirrhosis, the expression of DMT1 and Iregl was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Iregl and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Iregl. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload.

Resistance of three different populations of mulberry silkworm (Bombyx mori L.) to Bacillus thuringiensis

The relative resistance levels of three different populations of mulberry silkworm, Bombyx mori L. to Bacillus thuringiensis (Bt) has been studied. All three populations (two Australian and one Indonesian) were observed for similar characteristics including 3rd instar larval mortality at 24, 48, 72 and 96 h after treatment (HAT), LD50 ratio and probit mortality. Among the Australian two populations, the QuBill (yellow coloured, oval shaped cocoon) population showed higher larval mortality to Bt toxicity compared to the QuBite (white coloured, oval shaped cocoon) population. When all the populations were compared, the Insab (Indonesian population with white Coloured, peanut shaped cocoon) showed lower larval mortality and highest LD50 ratio up to 48 HAT. The Insab population also showed a 24 It longer incubation/latent period prior to the start Of Mortality.