Lake eutrophication and its implications for organic carbon sequestration in Europe.

The eutrophication of lowland lakes in Europe by excess nitrogen (N) and phosphorus (P) is severe because of the long history of land-cover change and agricultural intensification. The ecological and socio-economic effects of eutrophication are well understood but its effect on organic carbon (OC) sequestration by lakes and its change overtime has not been determined. Here, we compile data from ~90 culturally impacted European lakes [~60% are eutrophic, Total P (TP) >30 µg P l(-1) ] and determine the extent to which OC burial rates have increased over the past 100-150 years. The average focussing corrected, OC accumulation rate (C ARFC ) for the period 1950-1990 was ~60 g C m(-2) yr(-1) , and for lakes with >100 µg TP l(-1) the average was ~100 g C m(-2) yr(-1) . The ratio of post-1950 to 1900-1950 C AR is low (~1.5) indicating that C accumulation rates have been high throughout the 20th century. Compared to background estimates of OC burial (~5-10 g C m(-2) yr(-1) ), contemporary rates have increased by at least four to fivefold. The statistical relationship between C ARFC and TP derived from this study (r(2) = 0.5) can be used to estimate OC burial at sites lacking estimates of sediment C-burial. The implications of eutrophication, diagenesis, lake morphometry and sediment focussing as controls of OC burial rates are considered. A conservative interpretation of the results of the this study suggests that lowland European meso- to eutrophic lakes with >30 µg TP l(-1) had OC burial rates in excess of 50 g C m(-2) yr(-1) over the past century, indicating that previous estimates of regional lake OC burial have seriously underestimated their contribution to European carbon sequestration. Enhanced OC burial by lakes is one positive side-effect of the otherwise negative impact of the anthropogenic disruption of nutrient cycles.

The Eocene Arctic Azolla bloom: environmental conditions, productivity and carbon drawdown.

Enormous quantities of the free-floating freshwater fern Azolla grew and reproduced in situ in the Arctic Ocean during the middle Eocene, as was demonstrated by microscopic analysis of microlaminated sediments recovered from the Lomonosov Ridge during Integrated Ocean Drilling Program (IODP) Expedition 302. The timing of the Azolla phase (approximately 48.5 Ma) coincides with the earliest signs of onset of the transition from a greenhouse towards the modern icehouse Earth. The sustained growth of Azolla, currently ranking among the fastest growing plants on Earth, in a major anoxic oceanic basin may have contributed to decreasing atmospheric pCO2 levels via burial of Azolla-derived organic matter. The consequences of these enormous Azolla blooms for regional and global nutrient and carbon cycles are still largely unknown. Cultivation experiments have been set up to investigate the influence of elevated pCO2 on Azolla growth, showing a marked increase in Azolla productivity under elevated (760 and 1910 ppm) pCO2 conditions. The combined results of organic carbon, sulphur, nitrogen content and 15N and 13C measurements of sediments from the Azolla interval illustrate the potential contribution of nitrogen fixation in a euxinic stratified Eocene Arctic. Flux calculations were used to quantitatively reconstruct the potential storage of carbon (0.9-3.5 10(18) gC) in the Arctic during the Azolla interval. It is estimated that storing 0.9 10(18) to 3.5 10(18) g carbon would result in a 55 to 470 ppm drawdown of pCO2 under Eocene conditions, indicating that the Arctic Azolla blooms may have had a significant effect on global atmospheric pCO2 levels through enhanced burial of organic matter.

1-Benzyl-3,3-dichloro-1H-indol-2(3H)-one.

The title compound, C(15)H(11)Cl(2)NO, was synthesized from N-benzyl isatin. The compound crystallizes as stacks of molecules running down the c axis. Molecules within each of these stacks interact with each other through pi-pi and C-H...pi interactions, and interact with neighbouring stacks through C-H...O interactions.

Fatal occupational inhalation of hydrogen sulfide.

A young man aged 22 years, a sewer worker by profession, died after massive inhalation of hydrogen sulfide while at work. He was rescued by the emergency services and admitted to the critical care department, where he died due to massive myocardial necrosis less than 24 h after admission. In this case, where the causes of the accident were not clearly established, autopsy and anatomopathologic examination made it possible to confirm the causal lesions which resulted in death and to question the initial version of the circumstances of the accident. Medicolegal investigation was valuable in determining possible liabilities and repercussions on coverage as an industrial accident by the national health insurance system.

Correlation between in vitro release from topical delivery vehicles and microbicidal activity of triclosan.

This study reports the formulation, stability, in vitro release and microbicidal activity of a cream, emulsion, foot gel, cover stick and after sun spray containing triclosan. Triclosan is a broad-spectrum antimicrobial agent with activity against a wide range of both gram-negative and gram-positive bacteria that has found increasing popular use in personal care products. These products were stable for up to 3 months when stored at 5, 25, and 40 degrees C. Antimicrobial zone inhibition tests showed that that was a liner relationship, R2 > 0.92, between the release of triclosan from these products and the size of the inhibition zones. This means the in vitro/in vivo correlation for these products was good and that release studies can be used to predict the antimicrobial activity of triclosan.

Atmospheric detection of water dimers via near-infrared absorption.

Weakly bonded pairs of water molecules (H2O)2, or water dimers (WDs), may play an important role in photochemistry and climate, but the overlap of most of its spectral features with the water monomer (WM) has made detection difficult. We report on WD absorption measurements by means of atmospheric long-path (18.34 kilometers) differential optical absorption spectroscopy of the near-infrared OH stretching mode 0>f 4>b overtone transition predicted to be located near 746 nanometers. Our observation is in reasonable agreement with the known thermochemistry, calculated and measured structure, and spectroscopy (band strength, shape, and width) of the WD. The observation implies that the WD 0>f 4>b band is located at 749.5 nanometers, with a full width at half maximum of approximately 19.4 wave numbers, and that its band strength ranges between 1.23 x 10(-22) and 5.25 x 10(-22) centimeters per molecule.

Structure analysis of high resolution magnetic resonance imaging of the proximal femur: in vitro correlation with biomechanical strength and BMD.

The purpose of this study was to use high resolution magnetic resonance imaging (HR-MRI) combined with structure analysis to investigate the trabecular structure of the human proximal femur and to compare this technique with bone mineral density (BMD) using dual energy X-ray absorptiometry (DXA) in the prediction of bone strength in vitro. Thirty-one fresh human proximal femur specimens were examined with HR-MRI using a T1-weighted 3D spinecho-sequence in a coronal plane (voxel size: 0.195 x 0.195 x 0.9 mm and 0.195 x 0.195 x 0.3 mm). In these images structure parameters analogous to standard bone histomorphometry were obtained in a femoral head, neck, and trochanteric region of interest (ROI). In addition, BMD measurements were obtained using DXA and finally, all specimens were tested biomechanically in a materials testing machine, and maximum compressive strength (MCS) was determined. Correlations between BMD and MCS were significant (p <0.01) with R-values up to 0.74. Correlating structure parameters and MCS R-values up to 0.69 (P <0.01) were obtained. Using multivariate regression analysis, combining structure parameters and BMD, improved correlations versus MCS substantially (up to R = 0.93; P <0.01). In conclusion, this study showed that in an experimental setting, structure parameters determined in high resolution MR images of the proximal femur correlated significantly with bone strength. The highest correlations, however, were obtained combining BMD and structure measures.

Does the trabecular bone structure depicted by high-resolution MRI of the calcaneus reflect the true bone structure?

RATIONALE AND OBJECTIVES: The purpose of this study was to compare trabecular bone structure parameters assessed with high-resolution magnetic resonance imaging (HR-MRI) with those determined in specimen sections. METHODS: High-resolution MR images were obtained for 30 calcaneus specimens with a three-dimensional, T1-weighted spin-echo sequence (spatial in-plane resolution 0.195 mm, slice thicknesses of 0.3 and 0.9 mm). Thirty-eight sections were obtained from the specimens, and contact radiography was performed. In the corresponding sections, structural parameters analogous to bone histomorphometry were determined. RESULTS: Significant correlations between MRI-derived structural parameters and those derived from macro pathological sections were found: r values of up to 0.75 were obtained (P < 0.01). The highest correlations were found for apparent bone volume/total volume and trabecular thickness. Image thresholding techniques showed a significant impact on these correlations (P < 0.01). The thinner MR sections were less susceptible to the different thresholding algorithms. CONCLUSIONS: Trabecular bone structure depicted by HR-MR images is significantly correlated with that shown in macro sections (P < 0.01); however, a number of limitations have to be considered, including the substantial impact of thresholding techniques and slice thickness.

Characterization of the solubility and dissolution properties of several new rifampicin polymorphs, solvates, and hydrates.

Based on reports that tuberculosis is on the increase, this investigation into the physicochemical properties of rifampicin when recrystallized from various solvent systems was undertaken. Rifampicin is an essential component of the currently recommended regimen for treating tuberculosis, although relatively little is known about its solubility and dissolution behavior in relation to its solid-state properties. A rifampicin monohydrate, a rifampicin dihydrate, two amorphous forms, a 1:1 rifampicin:acetone solvate, and a 1:2 rifampicin:2-pyrrolidone solvate were isolated and characterized using spectral, thermal, and solubility measurements. The crystal forms were relatively unstable because except for the 2-pyrrolidone solvate, all the hydrated or solvated materials changed to amorphous forms after desolvation. Fourier transform infrared (FTIR) analysis confirmed the favorable three-dimensional organization of the pharmacophore to ensure antibacterial activity in all the crystal forms except the 2-pyrrolidone solvate. In the 2-pyrrolidone solvate, the strong IR signals of 2-pyrrolidone interfered with the vibrations of the ansa group. The 2-pyrrolidone solvate was the most soluble in phosphate buffer at pH 7.4. This solvate also had the highest solubility (1.58 mg/ml) and the fastest dissolution in water. In 0.1 M HCl, the dihydrate dissolved the quickest. A X-ray amorphous form (amorph II) was the least soluble and had the slowest dissolution rate because the powder was poorly wettable and very electrostatic.

Changes in calcaneal trabecular bone structure after heart transplantation: an MR imaging study.

PURPOSE: To use high-spatial-resolution magnetic resonance (MR) imaging to analyze the trabecular bone structure of the calcaneus in patients before and after heart transplantation and to compare this technique with bone mineral density (BMD) measurement in predicting therapy-induced bone loss and vertebral fracture status. MATERIALS AND METHODS: High-spatial-resolution 1.5-T MR imaging of the calcaneus was performed in 40 men 11-120 months after heart transplantation, in 11 men before heart transplantation, and in 10 age-matched male volunteers. Sagittal and transverse T1-weighted spin-echo images with a voxel size of 0.195 x 0.195 x 1.000 mm were obtained, and structure measurements analogous to bone histomorphometric values were calculated. In addition, the BMD of the lumbar spine was determined in the transplant recipients pre- and postoperatively by using quantitative computed tomography, and vertebral fracture status was assessed. RESULTS: Significant differences in structure and BMD measurements were found between patients before and after heart transplantation (P <. 05). In 17 (42%) of 40 transplant recipients, vertebral fractures were found. Although structure measurements were significantly different between patients with and those without fractures (P <.05), BMDs were not. Correlations between time after transplantation and some structure measurements were moderately significant (P <. 05), but such correlations with BMD measurements were not. CONCLUSION: MR imaging-derived structure measurements in the calcaneus are useful for monitoring bone changes after heart transplantation and assessing vertebral fracture status.

Characterization of zopiclone crystal forms found among generic raw materials.

This paper deals with the occurrence of polymorphs and pseudopolymorphs and their effect on the solid-state properties of zopiclone, a poorly water soluble nondiazepine sedative and hypnotic drug. X-ray powder diffraction (XRPD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), particle size analysis, dissolution studies, and solubility determinations were used to characterize the zopiclone raw materials. An anhydrated form, a dihydrated form, and a mixture of these two crystal forms were found and characterized among the zopiclone powders.

Solubility and dissolution properties of generic rifampicin raw materials.

Rifampicin shows polymorphism; therefore, it is necessary to select a suitable crystal form at an early stage of development to ensure optimum solubility and dissolution rates. This study was an investigation into the crystal properties of several rifampicin raw materials currently being used by manufacturers of generic rifampicin raw materials in South Africa. Powders were characterized by X-ray diffraction (XRD), infrared (IR) spectroscopy, and differential scanning calorimetry (DSC). The solubility in water and dissolution properties in water, buffer pH 7.4 and 0.1 M HCl, were also measured. The main difference between the powders was the amorphous content. XRD, IR, and DSC methods could detect the presence of amorphous rifampicin. In contrast to expectations, an increase in amorphous content significantly reduced the dissolution rate of the powders in water and buffer pH 7.4. This behavior was attributed to the electrostatic properties of the very fine particles in the amorphous powders. The results of this study showed that the physical properties of rifampicin raw materials varied not only among manufacturers, but also among batches from the same manufacturer.

The diagnosis and management of insomnia in clinical practice: a practical evidence-based approach.

Insomnia, or the dissatisfaction with the quantity, quality or timing of sleep, is a common complaint. Because the definition of "normal" sleep is not well established, the estimates of the prevalence and severity of insomnia vary widely. Insomnia is often secondary to underlying psychiatric and medical conditions, and these should be evaluated and treated as a first measure. Nonpharmacological interventions for insomnia including sleep hygiene manoeuvres and exercise are recommended, although the success of these interventions has not been well documented. Benzodiazepines have been the pharmacologic agents of choice for the treatment of insomnia, but there is reason to exercise caution with their use; their overall benefit compared with placebo appears to be minor, and they are often associated with adverse cognitive effects. Unfortunately, no other class of drugs has proven to be superior to the benzodiazepines in terms of benefit:risk ratio. Given the importance of sleep for health and normal daily functioning the diagnosis, prognosis and treatment of insomnia should be a research priority.

Meta-analysis of benzodiazepine use in the treatment of insomnia.

OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable.

The effect of polymorphism on powder compaction and dissolution properties of chemically equivalent oxytetracycline hydrochloride powders.

In South Africa, oxytetracycline is identified as an essential drug; many generic products are on the market, and many more are being developed. In this study, six oxytetracycline hydrochloride powders were obtained randomly from manufacturers, and suppliers were compared. It was found that compliance to a pharmacopoeial monograph was insufficient to ensure the optimum dissolution performance of a simple tablet formulation. Comparative physicochemical raw material analysis showed no major differences with regard to differential scanning calorimetry (DSC), infrared (IR) spectroscopy, powder dissolution, and particle size. However, the samples could be divided into two distinct types with respect to X-ray powder diffraction (XRD) and thus polymorphism. The two polymorphic forms had different dissolution properties in water or 0.1 N hydrochloride acid. This difference became substantial when the dissolution from tablets was compared. The powders containing form A were less soluble than that containing form B.

Preformulation stability screening of ivermectin with non-ionic emulsion excipients.

As an important and complementary step during a preformulation study differential scanning calorimetry (DSC) and high-pressure liquid chromatography (HPLC) were used to determine the compatibility between ivermectin and commonly used excipients for preparing non-ionic emulsions. Ivermectin was found to exhibit interactions with 21 excipients, while it was compatible with 25 excipients. HPLC showed a significant decrease in drug amount +20%, when substances interacted with invermectin.

Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal.

OBJECTIVE: To analyse the evidence for the efficacy and potential harmful effects of benzodiazepines compared with other therapies in the treatment of acute alcohol withdrawal. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1997 that described randomized controlled trials (RCTs) of benzodiazepines in the treatment of acute alcohol withdrawal. Key words included "benzodiazepines" (exploded) and "randomized controlled trial." Bibliographies of relevant articles were reviewed for additional RCTs, and manufacturers of benzodiazepines were asked to submit additional RCT reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were RCTs involving patients experiencing acute alcohol withdrawal and comparing a benzodiazepine available in Canada with placebo or an active control drug. Of the original 23 trials identified, 11 met these criteria, representing a total of 1286 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analysis of benefit (therapeutic success within 2 days) showed that benzodiazepines were superior to placebo (common odds ratio [OR] 3.28, 95% confidence interval [CI] 1.30-8.28). Data on comparisons between benzodiazepines and other drugs, including beta-blockers, carbamazepine and clonidine, could not be pooled, but none of the alternative drugs was found to be clearly more beneficial than the benzodiazepines. The meta-analysis of harm revealed no significant difference between benzodiazepines and alternative drugs in terms of adverse events (common OR 0.67, 95% CI 0.34-1.32) or dropout rates (common OR 0.68, 95% CI 0.47-0.97). INTERPRETATION: Benzodiazepines should remain the drugs of choice for the treatment of acute alcohol withdrawal.

Diagnosis and management of acute alcohol withdrawal.

Alcohol abuse produces a considerable burden of illness in the Canadian population. The diagnosis of alcohol dependence and withdrawal can be difficult, particularly in the setting of covert intake or comorbidity. Two validated scales, the CAGE questionnaire to screen for alcohol abuse and dependence and the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale to assess the severity of withdrawal, are valuable tools for clinicians to use on a regular basis. For the treatment of alcohol withdrawal, compelling anecdotal evidence supports the routine administration of thiamine, but not necessarily other vitamins. Phenytoin has not been shown to be superior to placebo for uncomplicated withdrawal seizures. Neuroleptics are not recommended for routine use. Sedation with benzodiazepines guided by the CIWA-Ar results is recommended. There is good evidence that the management of alcohol withdrawal can be improved with the routine use of the CIWA-Ar scale to assess severity, treatment with adequate doses of benzodiazepines and follow-up monitoring of patients in alcohol withdrawal.

A study of the changes during heating of paracetamol.

The orthorhombic form of paracetamol has been shown to exhibit greater compressibility and faster dissolution than the monoclinic form. The orthorhombic form is produced by melting of monoclinic crystals of paracetamol followed by cooling at specific rates. Cooling rate, although a very important factor, is not the only factor influencing the formation of either of the two morphs. To study the cooling rate required for production of form II, paracetamol samples were melted in a differential scanning calorimeter, cooled at three specific rates, and melted again. In all of the samples, cooling resulted in the glassy form followed by recrystallization and the melting of form II. On the hot-stage microscope both forms were produced in one sample. Standardizing conditions for prediction of the resulting form remains a problem. There seems to be a great deal of overlap of the two forms' transition phases, which would make it difficult to force the crystallization of one form by keeping the solution or melt at a specific temperature. The thermal behavior of paracetamol during the heating and cooling phases must be understood in order to manipulate the process. A video camera mounted on a hot-stage microscope was used to follow the changes during heating and cooling of both forms. Nucleation, crystal growth, habit transformation, sublimation, and the final melt are shown on snap shots taken from the video.