CO2 storage and release in the deep Southern Ocean on millennial to centennial timescales.

The cause of changes in atmospheric carbon dioxide (CO2) during the recent ice ages is yet to be fully explained. Most mechanisms for glacial-interglacial CO2 change have centred on carbon exchange with the deep ocean, owing to its large size and relatively rapid exchange with the atmosphere1. The Southern Ocean is thought to have a key role in this exchange, as much of the deep ocean is ventilated to the atmosphere in this region2. However, it is difficult to reconstruct changes in deep Southern Ocean carbon storage, so few direct tests of this hypothesis have been carried out. Here we present deep-sea coral boron isotope data that track the pH-and thus the CO2 chemistry-of the deep Southern Ocean over the past forty thousand years. At sites closest to the Antarctic continental margin, and most influenced by the deep southern waters that form the ocean's lower overturning cell, we find a close relationship between ocean pH and atmospheric CO2: during intervals of low CO2, ocean pH is low, reflecting enhanced ocean carbon storage; and during intervals of rising CO2, ocean pH rises, reflecting loss of carbon from the ocean to the atmosphere. Correspondingly, at shallower sites we find rapid (millennial- to centennial-scale) decreases in pH during abrupt increases in CO2, reflecting the rapid transfer of carbon from the deep ocean to the upper ocean and atmosphere. Our findings confirm the importance of the deep Southern Ocean in ice-age CO2 change, and show that deep-ocean CO2 release can occur as a dynamic feedback to rapid climate change on centennial timescales.

Acute cardiotoxicity induced by doxorubicin in right ventricle is associated with increase of oxidative stress and apoptosis in rats.

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents, but its efficiency is seriously limited by the risk of developing cardiomyopathy. The most recognized cardiotoxic effect is left ventricular (LF) dysfunction, but MRI and echocardiography data demonstrated significant right ventricle (RV) function impairment. In order to clarify this aspect, the present study investigated the potential of DOX to induce acute RV cardiotoxicity at the same time as LV impairment. Rats were intraperitoneally (i.p.) injected with a single dose of 15 mg/kg DOX. DOX-treated rats were characterized by decreased body and heart weights, elevated levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) activities compared to controls. Biochemical analyses on RV tissue revealed that the level of malondialdehyde (MDA) was significant increased (p<0.05) and activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPX) antioxidant enzymes were decreased by 13%, 27% and 18%, respectively, compared to control. Histopathogical and electron microscopic studies revealed DOX-induced damage in both ventricles and an increase of interstitial collagen fibers compared to controls (p<0.001), whereas immunohistochemical analysis showed weak and irregular desmin expression. Furthermore, mitochondrion-induced apoptotic pathways were also activated in both ventricles, as reflected by the up-regulation of Bax/Bcl-2 mRNA expression ratio (p<0.001) and increase of Bax and caspase-3 protein expression, as well as by the significant elevation of TUNEL positive nuclei, compared to controls (p<0.001). The results showed that DOX exerted RV toxic effects at the same time as those reported in the LV, which might be mediated through the mitochondrial-dependent apoptosis.

Radon and radium concentration in water from North-West of Romania and the estimated doses.

In the present study, the measurements of radon were carried out using the LUK-VR system based on radon gas measurements with Lucas cells. The radium concentration in water was determined, with the same device, immediately after was established the radon equilibrium with radium. The results presented here are from a survey carried out in the N-W region of Transylvania (Romania) in which were investigated the radon concentrations in natural (spring, well and surface) and drinking (tap) waters. The results showed radon concentrations within the range of 0.4-187.3 Bq l(-1) with an average value of 15.9 Bq l(-1) whereas radium concentration varied between 0.05 and 0.825 Bq l(-1) with an average value of 0.087 Bq l(-1) for all types of water covered within this survey. The corresponding annual effective ingestion dose due to radon and radium from water was determined from drinking water used by the population inhabiting the area.

Anti-inflammatory effect of Chandrashura (Lepidium sativum Linn.) an experimental study.

Lepidium sativum Linn. (Chandrashura) of Family Cruciferae (Brassicaceae) is being used by the people of Gujarat for treating inflammatory condition like arthritis. To evaluate its anti-inflammatory activity, Charles Foster albino rats were selected and experiments were carried out in three groups, therapeutic dose group, twice of therapeutic dose group and control group. In Carrageenan-induced paw oedema, the test drug produced moderate anti-inflammatory activity; however, the effect did not show statistically significant activity due to variation in the data of the control group. In formaldehyde-induced paw oedema in rats, the test drug produced moderate to significant suppression. This indicates that Chandrashura has a strong inhibitory effect on proliferation of fibroblasts and also probably has connective tissue modulation effect.

Indicators of the Fukushima radioactive release in NW Romania.

As a result of the Fukushima nuclear release, (131)I was found in different environmental media (rainwater, sheep and cow milk, herbage, sheep meat and thyroid tissue) in north-west Romania. On April 4, 2011 a maximum value of 1.40 ± 0.21 Bq/L in (131)I activity was found in rainwater obtained from the Arad region. The obtained value corresponded with the maximum of (131)I concentration in air, as measured by Toma et al. (2011) for the Pitesti area. One day later, sheep milk from the Cluj area was found to contain a maximum activity of 9.22 ± 0.95 Bq/L. A value of 0.85 ± 0.07 µSv was calculated as the total monthly effective dose received by the population as a result of the ingestion of sheep milk and sheep meat contaminated with (131)I. Only rainwater samples contained (134)Cs and (137)Cs at levels close to minimum detectable activity. Since the determined values could be influenced by Chernobyl (137)Cs, the (137)Cs concentrations are subject to uncertainty. The radioiodine transfer coefficients (Fm) and the concentration ratio (CR) from herbage to sheep milk, as well as sheep meat, from the Cluj-Apahida area are also presented.

Pharmacognostic study of Lepidium sativum Linn (Chandrashura).

Pharmacognosy is the study of naturally occurring biological substances, principally those derived from plants that find use in medicine. The word "Pharmacognosy" is derived from the Greek "Pharmacon," "a drug" and "gignosco," to acquire knowledge of. It is closely related to both botany and plant chemistry and both originated from the earlier scientific studies on medicinal plant. The plant kingdom still holds many species of plants containing substances of medicinal value which have yet to be discovered large number of plants constantly being screened for their possible pharmacological value. The plant Chandrashura is being used for the treatment of Amavata, Sandhivata, and Katishula successfully. Here, an attempt is made to study the plant pharmacognostically; the part taken for study is the seed. Diagnostic features of seed and seed powder were also worked out and the details were presented.

Recommendations for enhancing clinical trials education: a review of the literature.

This study aims to apply the evidence-based practice (EBP) process to determine the factors that influence patients' understanding of, participation in, and satisfaction with clinical trials, the informed consent process, and treatment decisions and to make recommendations for improving clinical trials education. Beginning with evidence retrieval, the authors identified key search terms and searched MEDLINE--Ovid, MEDLINE--PubMed, and the Cumulative Index to Nursing and Allied Health Literature to identify articles published between July 2001 and July 2006 that highlighted clinical trials education. The articles were reviewed for clinical trials patient education information, clinician methods of communicating clinical trial information to patients, and patient satisfaction with the clinical trials process, including the informed consent process. As a result, practice changes were recommended for the patient/family, staff/community, and institution. From the literature review, 81 articles were identified. Recurring themes included decision-making, patient education, staff education, and pediatrics. Most articles focused on methods and strategies aimed at improving education at the patient/family, staff/community, and institutional levels. The issues surrounding clinical trial education are complex due to multiple variables interfering with poor patient understanding of, participation in, and satisfaction with clinical trial treatment decisions. On the basis of our findings, we recommend that clinicians involved in educating patients, families, staff, and communities about clinical trials have an awareness of and understanding for very complex issues.

Analgesic effect of Lepidium sativum Linn. (Chandrashura) in experimental animals.

Lepidium sativum Linn, which is known as "Aselio" locally, is frequently used by the villagers for the treatment of Sandhivata (osteoarthritis), with good therapeutic relief. Here, we have to observe the analgesic activity of the seed of Lepidium sativum Linn in albino rats and Swiss albino mice with different parameters. The analgesic study was performed with acetic acid-induced writhing response in mice, formaldehyde-induced paw licking response in rats and tail flick response in mice. Experiments were carried out in two groups - therapeutic dose group and double dose group - with comparison with the control group. In the acetic acid-induced writhing syndrome, latency of onset was highly significantly increased in the therapeutic dose group and significant increase was found in the double dose group. In the formaldehyde-induced paw licking response, the test drug produced significant inhibition of neurogenic pain in the double dose group and significant inhibition of inflammatory pain in the therapeutic dose group. In the tail flick response, the test drug produced a mild to moderate effect in the therapeutic dose group and also in the double dose group.

Endogenous activation of adenosine A1 receptors promotes post-ischemic electrocortical burst suppression.

Following transient global cerebral ischemia (GCI), spontaneous electrocortical activity resumes from the isoelectric line through a sequence of "bursts" of activity alternating with periods of electrical "suppression," commonly referred to as the post-ischemic burst suppression (BS) pattern. Several lines of evidence suggest that BS reflects an impairment of neocortical connectivity. Here we tested in vivo whether synaptic depression by adenosine A1 receptor (A1R) activation contributes to BS patterns following GCI. Male Wistar rats were subjected to 1, 5 or 10 min of GCI using a "four-vessel occlusion" model under chloral hydrate anesthesia. Quantification of BS recovery was carried out using BS ratio. During GCI full electrocortical suppression was attained (BS ratio reached 100%). During the following reperfusion the BS ratio returned to 0. The time course of the decay was exponential after 1 and 5-min GCI and bi-exponential after 10-min GCI. The BS recovery was progressively delayed with the duration of ischemia. Administration of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 1.25 mg/kg i.p.) accelerated the post-ischemic BS recovery for all GCI durations. Following the 10-min GCI the effect of DPCPX was only apparent on the initial fast decay of the BS ratio. These data suggest that endogenous adenosine release promotes BS patterns during reperfusion following transient cerebral ischemia. Furthermore, the endogenous A1R activation may be the primary underlying cause of post-ischemic BS patterns following brief ischemic episodes. It is likely that synaptic depression by post-ischemic A1R activation functionally disrupts the connectivity within the cortical networks to an extent that promotes BS patterns.

Mitochondria, endoplasmic reticulum, and alternative pathways of cell death in critical illness.

Dying cells are distinguished by their biochemical and morphologic traits and categorized into three subtypes: apoptosis, oncosis (necrosis), and cell death with autophagy. Each of these types of cell death plays critical roles in tissue morphogenesis during normal development and in the pathogenesis of human diseases. Given that tissue homeostasis is controlled by the intricate balance between degeneration and regeneration, it is essential to understand the mechanisms of different forms of cell death to establish and improve therapeutic interventions for prevention and rescue of these cell death-related disorders. Critical illness, including sepsis, trauma, and burn injury, is often complicated by multiple organ dysfunction syndrome and is accompanied by increased cell death in parenchymal and nonparenchymal tissues. Accumulating evidence suggests that augmented cell death plays an important role in the organ failure in critical illness. We discuss possible therapeutic approaches for prevention of cell death, particularly apoptotic cell death.

Callosal responses of fast-rhythmic-bursting neurons during slow oscillation in cats.

The cortically generated slow oscillation consists of long-lasting hyperpolarizations associated with depth-positive electroencephalogram (EEG) waves and neuronal depolarizations accompanied by firing during the depth-negative EEG waves. It has previously been shown that, during the prolonged hyperpolarizations, the transfer of information from prethalamic pathways to neocortex is impaired, whereas the intracortical dialogue is maintained. To study some of the factors that may account for the maintenance of the intracortical information transfer during the hyperpolarization, intracellular recordings from association areas 5 and 7 were performed in anesthetized cats, and the synaptic responsiveness of fast-rhythmic-bursting, regular-spiking and fast-spiking neurons was tested using single pulses to the homotopic sites in the contralateral areas. During the long-lasting hyperpolarizations callosal volleys elicited in fast-rhythmic-bursting neurons, but not in regular-spiking or fast-spiking neurons, large-amplitude excitatory post-synaptic potentials crowned by single action potentials or spike clusters. Our data show that callosal volleys excite and lead to spiking in fast-rhythmic-bursting neurons during prolonged hyperpolarizations, thus enabling them to transmit information within intracortical networks during slow-wave sleep.

Long-term effects of botulinum toxin on neuromuscular function.

BACKGROUND: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium. METHODS: Rats (n=30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n=9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated. RESULTS: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups. CONCLUSION: Botulinum toxin causes dose-dependent long-term neuromuscular changes. The loss of tension generating capacity is almost exclusively related to muscle atrophy, because the specific tension did not change. The decreased ED10, unaltered ED50, and increased ED90 to atracurium suggest its interactions with different isoforms of receptors having varying sensitivity to atracurium. The absence of fade, despite the persistent botulinum toxin-induced denervation (increased nAChRs), suggests that the up-regulated nAChRs may have compensated for the prejunctional effects of botulinum toxin.

Hyperpolarisation rectification in cat lateral geniculate neurons modulated by intact corticothalamic projections.

The intrinsic properties of thalamic neurons are influenced by synaptic activities in ascending pathways and corticofugal projections, as well as by the actions of neurotransmitters released by generalised modulatory systems. We focused on the effects of corticothalamic projections on the hyperpolarisation-activated cation current Ih. Intracellular recordings of thalamocortical neurons in the dorsal lateral geniculate (dLG) nucleus were performed in cats under ketamine-xylazine anaesthesia. At variance with the conventional way of recording intracellularly from thalamic neurons after partial or total ablation of the grey and white matter overlying the dLG, we preserved intact corticothalamic neuronal loops. Stimulating electrodes inserted into the optic tract and light-emitting-diodes as photic stimulation were used to identify the dLG neurons. The expression of the depolarising sag due to Ih depended on the state of cortical networks. Thalamic dLG Ih, induced by hyperpolarising current steps, was detected during the periods of cortical disfacilitation that occur during the cortical slow (< 1 Hz) oscillation, whereas Ih was absent during the active (depolarised) periods. The possibility that the excitatory corticothalamic projections could preclude the generation of the Ih was tested by applying a concentrated K+ solution (3 M) to the primary visual cortex. The same dLG neurons that did not display Ih before application of K+ were able to produce hyperpolarisation-activated depolarising sags during K+-induced cortical depression. Our data suggest that the thalamic clock-like delta oscillation, which results from an interplay between Ih and the low-threshold calcium current (IT), as described in preparations without cerebral cortex, is prevented in dLG neurons when corticothalamic loops are intact.

Automation of a series of cutaneous topography measurements from silicon rubber replicas.

BACKGROUND/AIMS: Skin relief is a matter of interest for dermatologists and surgeons. One of the methods available for surface topography measurement is based on 3D profilometry using skin surface replicas. and most studies use statistical results obtained from a large number of skin replica samples. The advent of optical profilometers (without contact) made it possible to remove the solid positive replica and to reduce the duration of the profilometric data acquisition. Nevertheless this saving of time, to be really interesting, needs to automate the data acquisition on a series of negative replicas. METHODS/RESULTS: By adding a video camera to the optical profilometer and then by processing the resulting images, we have conceived a system able to carry out topographic measurements on a series of replicas loosely organized on a sample holder, without any human intervention. The silicon replicas in use have a very light colour: nearly white, sometimes slightly blue or green. The laser spot of the profilometer is so luminous that its red colour looks white through the camera. When choosing a replica holder with a matt dark colour and marking the left upper corner of the study area on the replica in black ink, the colours to be differentiated on the image are then close to the black one and the white one. We accordingly change the colour camera image into a black and white image (with 256 grey levels) and then carry out thresholdings to separate the different objects or information included in this image. With the use of a perfectly circular replica, of an accurately known size, laid on the sample holder at the center of the area filmed by the camera, we adjust the threshold level, which allows separation of the replica from its holder. We then move this calibrated replica in order to find the relationship between the size in pixels and the real size on the sample holder, in various positions of the video image. The software has four main built-in stages: Moving the sample holder beneath the sensor until a part of a replica is detected in the field of view of the camera; Moving the sample holder until this replica lies just in the middle of the image given by the camera; Recognition of the mark of the upper left corner of the surface area to be measured out inside this replica; and Moving the sample holder until the laser spot of the profilometer coincides with the origin of the surface area to be measured out, then carrying out this measurement. From the upper left corner of the sample holder, a scanning, line-by-line or column-by-column (according to the selected priority direction), is carried out until the successive replicas are found, and is stopped as soon as the number of replicas entered by the operator is reached. CONCLUSION: The simplicity of the algorithms used makes it possible to distinguish the next measurement area from the preceding one in a few seconds.

Oxidative damage following cerebral ischemia depends on reperfusion - a biochemical study in rat.

The extent of brain injury during reperfusion appears to depend on the experimental pattern of ischemia/reperfusion. The goals of this study were: first, to identify the rate of free radicals generation and the antioxidant activity during ischemia and reperfusion by means of biochemical measurement of lipid peroxidation (LPO) and both enzymatic (superoxide dismutase - SOD, catalase - CAT, glutathione peroxidase - GPx) and non-enzymatic antioxidants activity (glutathione - GSH); and second, to try to find out how the pattern of reperfusion may influence the balance between free radical production and clearance. Wistar male rats were subject of four-vessel occlusion model (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two atraumatic arterial microclamps placed on carotid arteries. The level of free radicals and the antioxidant activity were measured in ischemic rat brain tissue homogenate using spectrophotometrical techniques. All groups subjected to ischemia shown an increase of LPO and a reduction of the activity of enzymatic antioxidative systems (CAT, GPx, SOD) and non-enzymatic systems (GSH). For both groups subjected to ischemia and reperfusion, results shown an important increase of LPO but less significant than the levels found in the group with ischemia only. Statistically relevant differences (p<0.01) between continuous reperfusion and fragmented reperfusion were observed concerning the LPO, CAT, SOD and GSH levels, oxidative aggression during fragmented reperfusion being more important.

3-D profilometer using a CCD linear image sensor: application to skin surface topography measurement.

BACKGROUND/AIMS: Measurement of cutaneous surface topography can be made by three-dimensional (3-D) profilometry. Different equipment is used for this measurement. The magnitude of the vertical scale required, which can vary from several tens of micrometers (microrelief) to several millimeters (skin pathologies), depends also on the precision required and the duration of acquisition time. Over the last few years, different apparatuses have been produced, with a vertical range that is most frequently used for classical industrial applications, i.e., 0-1000 µm. METHODS: The system developed here has a wide range of about 7 mm and is accurate enough to analyse each of the different skin surfaces that fall in this range without changing magnification. An optical principle, operating without any contact with a skin replica, allows a precise measurement with a high scanning speed. RESULTS: The profilometer has a vertical sensitivity of 4 µm within a vertical range of 7 mm. This sensitivity is lower than that of a mechanical or focusing profilometer, but the vertical range is wider. CONCLUSIONS: The system has several advantages: because of its verticale range, it can measure large surfaces with great roughness variations; the initial position of the replica beneath the profilometer must be within the 7 mm vertical range; and skin topography can be quantified, without contact, in a short time.

The quantification of intrahemispheric EEG asymmetry in rat.

We have developed a simple model to quantify the intrahemispheric asymmetries (IA) present in the background EEG activity (BEA), of the adult rat during restrained wakefulness and anesthesia with Ether and chloral hydrate (CHL). We used a collectivity of 40 adult (140 g) male Wistar rats. The epidural EEG activity, was quantified within the 1-30 Hz band by six numerical parameters: root mean square (RMS), mean spectral frequency (MSF), spectral edge frequency at 95% (SEF95) and the relative spectral power (RSP) within the Theta (4.5-7.5 Hz), Alpha (7.5-12 Hz) and Beta (12.5-30 Hz) bands. A significant IA was considerate when simultaneously present in both hemispheres at p (t-Test) < 0.05. The only IA detected in the BEA of the awake restrained rat was the increased theta RSP over the fronto-parietal areas. The theta asymmetry was abolished under both types of anaesthesia. While ether had a global effect on BEA, CHL induced a strong IA reflected in all parameters except RMS and Theta RSP. The fronto-parietal areas seem to be relatively resistant to CHL. It is discussed that the intrahemispheric theta dominance over the frontoparietal areas should be regarded as an indicator of alertness in rats.

Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats.

Free radicals and platelet activating factor (PAF) have been implicated as important mediators in neuronal injury after cerebral ischemia-reperfusion and, particularly, in postischemic hypoperfusion. The electroencephalography (EEG) is a real time reflection of changes in neuronal activity and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats (p < 0.0015). Computerized spectral analysis of EEG has shown that the percentage of slow waves at 10 minutes after reperfusion was 117% higher in control group than in Ginkgo biloba group (p < 0.015) and the percentage of slow waves after 15 minutes of reperfusion was 100% higher in the control group than in the Ginkgo biloba group (p < 0.02). Five days after cerebral ischemia--reperfusion the percentage of slow waves was unsignificantly higher in the control group than in the Ginkgo biloba group (p > 0.05).