Seasonal variation of lead uptake in the earthworm Lumbricus terrestris and the influence of soil liming and acidification

The influence of seasonal temperature variations and liming and acidification of the soil on lead uptake in juveniles and adults of the earthworm species Lumbricus terrestris L. was studied by enclosing specimens for up to five months in net bags provided with lead-contaminated, sandy soil. Lead concentrations were analyzed in the pharynx, gizzard, muscles, seminal vesicles and cerebral ganglion. Lead distribution in whole animals was assessed after an injection of ²⁰³Pb. The lead concentrations of the tissues were mostly linearly correlated with the soil concentrations, which ranged from <0.5 to 310 mg/kg, and the highest concentrations were generally found in the ganglion. The effects on lead concentrations in tissues of lowered soil pH from 5.6 to 5.1 or raised to 5.9 were insignificant, though more lead became allocated to muscles than to ganglion when pH was lowered. The lead uptake was strongly dependent on the ambient temperature, especially in the muscles, and the concentrations were reduced by 50% or more during the cold spell in the winter season, presumably as a consequence of a low feeding activity. Though juveniles seemed more prone to take up lead, the concentrations were not significantly higher than those in adults during the winter period. The observations are discussed in the light of the use of earthworms in standardized programs for environmental hazard assessment, especially with respect to species and tissue selection.     

On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes

The cytotoxicity of acetaminophen (paracetamol) has been shown to be associated with a disruption of intracellular Ca2+ homeostasis caused by the interaction of its metabolite N-acetyl-p-benzoquinone imine (NAPQI) with hepatocyte thiols [Moore, M., et al. (1985) J. Biol. Chem. 260, 13035-13040]. Inasmuch as NAPQI can both covalently bind to thiols and oxidize thiols, we investigated the effects of two dimethylated analogues of NAPQI, one of which (2,6-dimethyl-NAPQI) primarily binds to thiols and the other of which (3,5-dimethyl-NAPQI) primarily oxidizes thiols. Of the three compounds, 2,6-dimethyl-NAPQI decreased protein thiols to the greatest extent and also inhibited hepatocyte plasma membrane Ca(2+)-ATPase to the greatest extent. The 3,5-dimethylated analogue decreased protein thiols to the least extent and inhibited the plasma membrane Ca(2+)-ATPase to a lesser extent. The cytotoxicity of all three compounds was preceded by a sustained elevation in cytosolic Ca2+ as compared to the transient rise caused by the alpha-agonist phenylephrine. Again, the 2,6-dimethyl analogue was the most potent of the three compounds. The thiol reagent dithiothreitol (DTT), which reversed the inhibition of the Ca(2+)-ATPase and the rise in cytosolic Ca2+, also protected against cytotoxicity. Agents that are known to inhibit either Ca(2+)-dependent proteases or phospholipases significantly delayed the onset of cytotoxicity caused by NAPQI and its analogues. Our results suggest that both arylation and oxidation of protein thiols may result in the elevation of cytosolic Ca2+ and in cytotoxicity and that arylation of critical thiol groups appears to be the more lethal reaction.     

Vasopressin release in response to acute hypotension induced at different time intervals in the conscious sheep

The renal arginine vasopressin (AVP) excretion in response to acute systemic hypotension induced by intravenous infusion of sodium nitroprusside (SNP) (30-40 micrograms/kg min-1) at different experiment intervals (0, 2, 4, 7 and greater than or equal to 12 days) was studied in the conscious hyperhydrated sheep. During the first post-infusion hour, 2.5 times more AVP was excreted in response to hypotension induced at greater than or equal to 12 day intervals than that observed at intervals of 0-7 days. No interexperimental time dependence of the AVP response to SNP infusion was seen with intervals of 0-7 days. The attenuated AVP release obtained with reduced experiment intervals (0-7 days) was accompanied by shorter antidiuresis and a less accentuated natriuresis during the post-hypotensive period in comparison to what was observed with greater than or equal to 12 day experiment intervals. There were no interval-dependent differences in maximal fall of mean arterial pressure, or onset and recovery of the hypotension induced by SNP administration. It is suggested that acute systemic hypotension causes such a massive AVP release that more than one week is needed for complete restoration of a releasable neurohypophyseal pool of the hormone.     

Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study

Purpose

To assess the ability of quantitative pupillometry [using the Neurological Pupil index (NPi)] to predict an unfavorable neurological outcome after cardiac arrest (CA).

Methods

We performed a prospective international multicenter study (10 centers) in adult comatose CA patients. Quantitative NPi and standard manual pupillary light reflex (sPLR)—blinded to clinicians and outcome assessors—were recorded in parallel from day 1 to 3 after CA. Primary study endpoint was to compare the value of NPi versus sPLR to predict 3-month Cerebral Performance Category (CPC), dichotomized as favorable (CPC 1–2: full recovery or moderate disability) versus unfavorable outcome (CPC 3–5: severe disability, vegetative state, or death).

Results

At any time between day 1 and 3, an NPi?≤?2 (n?=?456 patients) had a 51% (95% CI 49–53) negative predictive value and a 100% positive predictive value [PPV; 0% (0–2) false-positive rate], with a 100% (98–100) specificity and 32% (27–38) sensitivity for the prediction of unfavorable outcome. Compared with NPi, sPLR had significantly lower PPV and significantly lower specificity (p? <?0.001 at day 1 and 2; p ?=?0.06 at day 3). The combination of NPi?≤?2 with bilaterally absent somatosensory evoked potentials (SSEP; n?=?188 patients) provided higher sensitivity [58% (49–67) vs. 48% (39–57) for SSEP alone], with comparable specificity [100% (94–100)].

Conclusions

Quantitative NPi had excellent ability to predict an unfavorable outcome from day 1 after CA, with no false positives, and significantly higher specificity than standard manual pupillary examination. The addition of NPi to SSEP increased sensitivity of outcome prediction, while maintaining 100% specificity.

     

Effects of a training programme for elderly people on mineral content of the heel bone

Physical inactivity can cause rapid bone loss. Different forms of physical activity are recommended for osteoporosis. The scientific background for such recommendations, however, is usually weak.This study was performed to evaluate whether it is possible to influence bone mineral content in elderly people by regular exercise. A total of 15 women with a mean age of 72 yr took part in a study in which they were given 1 h of training twice a week for 9 mth. Physically inactive patients from an outpatient geriatric unit served as a control group. They were matched in age and did not suffer from diseases that affect the locomotor system.After 10 mth of training no significant increase in bone mineral content, measured in the heel bone, could be found among the participants in the training group. Bone mineral content in the trained subjects was however, significantly higher after this training period than in the control group. The decrease in bone mineral content in the control group was almost the same as in a representative group of the population aged 70 to 79 yr.The cause of the decreased loss of bone mineral content in the physically-active subjects in the study could not be determined, but some contributing factors are discussed. Thus, it appears that physical activity diminishes bone loss due to age and that physical training has a positive effect on bone mineral content compared to that of nonactive controls of the same age. As there are no negative side effects, it has advantages over other forms of therapy, such as pharmacological treatment.     

Clinical review: Continuous and simplified electroencephalography to monitor brain recovery after cardiac arrest

There has been a dramatic change in hospital care of cardiac arrest survivors in recent years, including the use of target temperature management (hypothermia). Clinical signs of recovery or deterioration, which previously could be observed, are now concealed by sedation, analgesia, and muscle paralysis. Seizures are common after cardiac arrest, but few centers can offer high-quality electroencephalography (EEG) monitoring around the clock. This is due primarily to its complexity and lack of resources but also to uncertainty regarding the clinical value of monitoring EEG and of treating post-ischemic electrographic seizures. Thanks to technical advances in recent years, EEG monitoring has become more available. Large amounts of EEG data can be linked within a hospital or between neighboring hospitals for expert opinion. Continuous EEG (cEEG) monitoring provides dynamic information and can be used to assess the evolution of EEG patterns and to detect seizures. cEEG can be made more simple by reducing the number of electrodes and by adding trend analysis to the original EEG curves. In our version of simplified cEEG, we combine a reduced montage, displaying two channels of the original EEG, with amplitude-integrated EEG trend curves (aEEG). This is a convenient method to monitor cerebral function in comatose patients after cardiac arrest but has yet to be validated against the gold standard, a multichannel cEEG. We recently proposed a simplified system for interpreting EEG rhythms after cardiac arrest, defining four major EEG patterns. In this topical review, we will discuss cEEG to monitor brain function after cardiac arrest in general and how a simplified cEEG, with a reduced number of electrodes and trend analysis, may facilitate and improve care.     

The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest

Introduction

Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability.

Methods

We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5).

Results

At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively.

Conclusions

The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.