Toxicity of three rare earth elements, and their combinations to algae, microcrustaceans, and fungi.

Rare earth elements (REEs) are naturally distributed in the environment, and are increasingly being used in agriculture and high technology materials worldwide, thereby increasing anthropogenic contamination and environmental risks. There exists scarce and contradictory toxicity information about REEs; hence, more studies are required, especially on their mixtures. Thus, this study aimed to assess the toxicities of La3+, Nd3+, Sm3+, and the combinations of these elements (binary 1:1 and ternary 1:1:1), to organisms from different trophic levels: producers (the microalgae Chlorella vulgaris and Raphidocelis subcapitata), primary consumers (the microcrustaceans Daphnia similis and Artemia salina), and decomposers (the fungi Penicillium simplicissimum and Aspergillus japonicus). Ecotoxicological bioassays were performed, and toxic concentrations were determined. Thereafter, toxicities of single and mixture REEs were classified as slightly to highly toxic according to their toxic units. Finally, a concentration addition (CA) model was used to estimate how REEs interact upon combining. Nd3+ was the most toxic element for all organisms, especially D. similis (48 h LC50 9.41 mg.L-1), and was therefore classified as highly toxic. Sm3+ promoted cell agglomeration in Chlorella vulgaris and was the most toxic of the tested elements for this organism (72 h IC50 25.78 mg.L-1). The CA model revealed synergistic responses for most of the combinations, principally Nd3+ + Sm3+, which was the most toxic combination for the tested organisms. Both fungi were the most resistant organisms, and A. japonicus produced exudate and sclerotia, which help in the detoxification of chemicals. Owing not only to the fact that fungi displayed a higher resistance to REEs, but also due to the absence of regulations for REEs released from the agricultural or industrial sector, and the lack of methods to treat effluents or to dispose of technological items containing REEs, these organisms should be considered as a model for the biosorption or bioremediation of REEs. Finally, the toxic effects of REEs, particularly Nd3+, on the biota and human health should be the focus of future studies due to their increased use in technology.

Do Riparian Buffers Protect Stream Invertebrate Communities in South American Atlantic Forest Agricultural Areas?

We investigated the influence and relative importance of insecticides and other agricultural stressors in determining variability in invertebrate communities in small streams in intensive soy-production regions of Brazil and Paraguay. In Paraguay we sampled 17 sites on tributaries of the Pirapó River in the state of Itapúa and in Brazil we sampled 18 sites on tributaries of the San Francisco River in the state of Paraná. The riparian buffer zones generally contained native Atlantic forest remnants and/or introduced tree species at various stages of growth. In Brazil the stream buffer width was negatively correlated with sediment insecticide concentrations and buffer width was found to have moderate importance in mitigating effects on some sensitive taxa such as mayflies. However, in both regions insecticides had low relative importance in explaining variability in invertebrate communities, while various habitat parameters were more important. In Brazil, the percent coverage of soft depositional sediment in streams was the most important agriculture-related explanatory variable, and the overall stream-habitat score was the most important variable in Paraguay streams. Paraguay and Brazil both have laws requiring forested riparian buffers. The ample forested riparian buffer zones typical of streams in these regions are likely to have mitigated the effects of pesticides on stream invertebrate communities. This study provides evidence that riparian buffer regulations in the Atlantic Forest region are protecting stream ecosystems from pesticides and other agricultural stressors. Further studies are needed to determine the minimum buffer widths necessary to achieve optimal protection.

The Danish Alzheimer intervention study: rationale, study design and baseline characteristics of the cohort.

BACKGROUND: There is a lack of appropriately designed trials investigating the efficacy of psychosocial interventions for patients with mild dementia and their family caregivers. This paper reports the rationale and design of the Danish Alzheimer Disease Intervention Study and baseline characteristics of the cohort. METHODS: The study was a 1-year multicentre randomized controlled rater-blinded trial with randomization to follow-up and a multifaceted semitailored intervention programme or to follow-up only (with extension of follow-up to 3 years). The intervention included a counselling programme, teaching courses, written information and logbooks. The outcomes included clinical efficacy parameters, patient satisfaction and health economic consequences. RESULTS: A total of 330 patients and their 330 caregivers were included during a period of 18 months. The majority (65.2 %) of the caregivers were spouses. At inclusion the mean age of the patients and caregivers was 76.2 and 66.0 years, respectively. CONCLUSION: The study will explore the added value of a multifaceted intervention programme and contribute to the design of future interventions for patients with mild dementia and their caregivers.

Impact of anti-cancer drugs and other determinants on serum protein binding of morphine 6-glucuronide.

BACKGROUND AND THE PURPOSE OF THE STUDY: The aim of the present study was to examine factors that may influence the protein binding of morphine 6-glucuronide (M6G), the most active metabolite of morphine. METHODS: An enzyme-linked immunoabsorbent assay technique was used to measure the M6G concentration in serum of 18 healthy adults, 18 neonatal and 7 children with cancer. Total and free M6G concentrations were measured following equilibrium dialysis for 3 hrs and at physiological pH at 37°C. The influence of vincristine, methotrexate, 6-mercaptopurine, morphine, human albumin, alpha-1-acid glycoprotein, palmitic acid, oleic acid and pH on M6G protein binding was examined. RESULTS: M6G was 66.87±0.73 percent free in human serum at physiological pH and temperature. The percentage free (unbound) was increased significantly by vincristine (4.33%) and methotrexate (9.68%), but 6- mercaptopurine and morphine had no significant effect on it. Free percentages of M6G was reduced by decreasing serum albumin concentration but was unaffected by the presence of alpa-1-acid glycoprotein (AAG) or changes in serum pH. Similar results were obtained in human serum albumin (HAS) solutions. Addition of palmitic acid and oleic acid reduced protein binding significantly by 6.3% and 7.4%, respectively. MAJOR CONCLUSION: Although M6G in this study was not highly bounded, but because of its high analgesic potency, any change in its free concentration due to concurrent medication or disease caused significant changes in its effects. This dearth of evidence has been implicated in the reluctance of professionals to be cautious in prescribing them to children, particularly in the neonatal period.

Biological stenciling of mineralization in the skeleton: Local enzymatic removal of inhibitors in the extracellular matrix.

Biomineralization is remarkably diverse and provides myriad functions across many organismal systems. Biomineralization processes typically produce hardened, hierarchically organized structures usually having nanostructured mineral assemblies that are formed through inorganic-organic (usually protein) interactions. Calcium­carbonate biomineral predominates in structures of small invertebrate organisms abundant in marine environments, particularly in shells (remarkably it is also found in the inner ear otoconia of vertebrates), whereas calcium-phosphate biomineral predominates in the skeletons and dentitions of both marine and terrestrial vertebrates, including humans. Reconciliation of the interplay between organic moieties and inorganic crystals in bones and teeth is a cornerstone of biomineralization research. Key molecular determinants of skeletal and dental mineralization have been identified in health and disease, and in pathologic ectopic calcification, ranging from small molecules such as pyrophosphate, to small membrane-bounded matrix vesicles shed from cells, and to noncollagenous extracellular matrix proteins such as osteopontin and their derived bioactive peptides. Beyond partly knowing the regulatory role of the direct actions of inhibitors on vertebrate mineralization, more recently the importance of their enzymatic removal from the extracellular matrix has become increasingly understood. Great progress has been made in deciphering the relationship between mineralization inhibitors and the enzymes that degrade them, and how adverse changes in this physiologic pathway (such as gene mutations causing disease) result in mineralization defects. Two examples of this are rare skeletal diseases having osteomalacia/odontomalacia (soft bones and teeth) - namely hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH) - where inactivating mutations occur in the gene for the enzymes tissue-nonspecific alkaline phosphatase (TNAP, TNSALP, ALPL) and phosphate-regulating endopeptidase homolog X-linked (PHEX), respectively. Here, we review and provide a concept for how existing and new information now comes together to describe the dual nature of regulation of mineralization - through systemic mineral ion homeostasis involving circulating factors, coupled with molecular determinants operating at the local level in the extracellular matrix. For the local mineralization events in the extracellular matrix, we present a focused concept in skeletal mineralization biology called the Stenciling Principle - a principle (building upon seminal work by Neuman and Fleisch) describing how the action of enzymes to remove tissue-resident inhibitors defines with precision the location and progression of mineralization.

Fermentation for Disinfesting Fruit Waste From Drosophila Species (Diptera: Drosophilidae).

Economic losses in a range of fruit crops due to the Drosophila suzukii (Matsumura) have become severe. Removal and treatment of fruit waste, which may harbor D. suzukii, is a key step in preventing reinfestation of fruit production. Natural fermentation for disinfesting fruit wastes from D. suzukii was examined at ambient air temperatures of 12-20 °C. Soft and stone fruit wastes infested with eggs, larvae, and pupae of Drosophila melanogaster (Meigen) or D. suzukii were placed in sealed vessels containing fruit wastes, and samples were retrieved at intervals and tested for the emergence of adults. Mean temperatures of the fruit waste in the sealed vessels during fermentation were 15-23 °C. Fermentation for 3 d was effective in disinfesting waste from different life stages of D. suzukii. Treatment for 4 d also ensured that the waste was free of viable life stages of D. melanogaster, which could be used as an indicator species for disinfestation of waste from D. suzukii owing to its greater tolerance of fermentation. The O2 concentration of the headspace air in the vessels became undetectable after 13-16 h, with a corresponding increase in CO2 concentration, which exceeded 80% vol/vol. The resulting hypoxia and hypercapnia may explain the efficacy of the fermentation treatment in disinfesting the waste. Fermented fruit remained attractive to D. suzukii and retained its capacity to rear a life cycle. Covering or mixing fermented fruit with a sufficient depth (0.1 m) or volume (×9) of soil or coir prevented the reinfestation of treated waste.

Localization of methyl benzoate synthesis and emission in Stephanotis floribunda and Nicotiana suaveolens flowers.

The emission of fragrances can qualitatively and quantitatively differ in different parts of flowers. A detailed analysis was initiated to localize the floral tissues and cells which contribute to scent synthesis in STEPHANOTIS FLORIBUNDA (Asclepiadaceae) and NICOTIANA SUAVEOLENS (Solanaceae). The emission of scent compounds in these species is primarily found in the lobes of the corollas and little/no emission can be attributed to other floral organs or tissues. The rim and centre of the petal lobes of S. FLORIBUNDA contribute equally to scent production since the amount of SAMT (salicylic acid carboxyl methyltransferase) and specific SAMT activity compensate each other in the rim region and centre region. IN SITU immunolocalizations with antibodies against the methyl benzoate and methyl salicylate-synthesizing enzyme indicate that the adaxial epidermis with few subepidermal cell layers of S. FLORIBUNDA is the site of SAMT accumulation. In N. SUAVEOLENS flowers, the petal rim emits twice as much methyl benzoate due to higher total protein concentrations in the rim versus the petal centre; and, both the adaxial and abaxial epidermis house the BSMT (salicylic acid/benzoic acid carboxyl methyltransferase).

Spatial and temporal distribution of benthic macroinvertebrates in a Southeastern Brazilian river.

Benthic macroinvertebrate assemblages are structured according to physical and chemical parameters that define microhabitats, including food supply, shelter to escape predators, and other biological parameters that influence reproductive success. The aim of this study is to investigate spatial and temporal distribution of macroinvertebrate assemblages at the Macaé river basin, in Rio de Janeiro state, Southeastern Brazil. According to the "Habitat Assessment Field Data Sheet--High Gradient Streams" (Barbour et al., 1999), the five sampling sites are considered as a reference condition. Despite the differences in hydrological parameters (mean width, depth and discharge) among sites, the physicochemical parameters and functional feeding groups' general structure were similar, except for the less impacted area, which showed more shredders. According to the Detrended Correspondence Analysis based on substrates, there is a clear distinction between pool and riffle assemblages. In fact, the riffle litter substrate had higher taxa in terms of richness and abundance, but the pool litter substrate had the greatest number of exclusive taxa. A Cluster Analysis based on sampling sites data showed that temporal variation was the main factor in structuring macroinvertebrate assemblages in the studied habitats.

Transport and metabolism of pyridoxine in rat liver.

Evidence, obtained with in situ perfused rat liver, indicated that pyridoxine is taken up from the perfusate by a non-concentrative process, followed by metabolic trapping. These conclusions were reached on the basis of the fact that at low concentrations (0.125 microM), the 3H of [3H]pyridoxine accumulated against a concentration gradient, but high concentrations (333 microM) of pyridoxine or 4-deoxypyridoxine prevented this apparent concentrative uptake. Under no conditions did the tissue water:perfusate concentration ratio of [3H]pyridoxine exceed unity. The perfused liver rapidly converted the labeled pyridoxine to pyridoxine phosphate, pyridoxal phosphate and pyridoxamine phosphate and released a substantial amount of pyridoxal and some pyridoxal phosphate into the perfusate. Since muscle and erythrocytes failed to oxidize pyridoxine phosphate to pyridoxal phosphate, it is suggested that the liver plays a major role in oxidizing dietary pyridoxine and pyridoxamine as their phosphate esters to supply pyridoxal phosphate which then reaches to other organs chiefly as circulating pyridoxal.

Low dose Ara-C for patients with myelodysplastic syndromes.

Forty patients with high risk myelodysplastic syndromes--refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia--were treated with subcutaneous low dose cytosine arabinoside, 10 mg/m2 twice daily for up to 42 days. In 38 evaluable patients there were nine (24%) complete and four (11%) partial responses. Response was associated with symptomatic improvement and resolution of the need for red cell and platelet transfusions. The median duration of complete response was 9.8 months (range, 2.4-17.9); these patients had a median survival of 15.7 months (range, 6.0-22.7). Toxicities were predominantly those associated with pancytopenia, i.e., infection and hemorrhage.

Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases.

PURPOSE: To determine the etiology and to evaluate the clinical consequences of an extremely elevated platelet count. PATIENTS AND METHODS: A review of the medical records was performed on all patients encountered during a 5 1/2-year period who had at least one platelet count of 1,000 x 10(9)/L or greater. RESULTS: Of the total of 280 patients with extreme thrombocytosis (EXT), 231 (82%) had reactive thrombocytosis (RT), 38 (14%) had a myeloproliferative disorder (MPD), and 11 (4%) had cases of uncertain etiology. RT was more common than MPD in all age groups except those in the eighth decade and older. Symptoms of bleeding and/or vaso-occlusive phenomena were noted in association with EXT in 21 (56%) of the MPD patients but in only 10 (4%) of the RT patients. Treatment to lower the platelet count and/or inhibit platelet function was employed in 36 MPD patients and 23 RT patients. Eight patients with MPD and 34 with RT are known to have died, but no patient in either group is known to have died of a thrombotic or bleeding event when the platelet count was greater than or equal to 1,000 x 10(9)/L. CONCLUSIONS: Platelet counts greater than or equal to 1,000 x 10(9)/L should not be considered rare events in the general, acute-care hospital population, and usually represent a reactive phenomenon.

Single high dose-large field irradiation in drug resistant non-Hodgkin's lymphoma.

Single high dose-large field irradiation (SHD-LFI), also described as half-body irradiation (HBI), has previously been reported as an effective modality for the palliation of symptoms in a number of solid tumors. This report concerns the ability of SHD-LFI to produce palliation of symptoms and/or objective response in patients with drug resistant non-Hodgkin's lymphoma (NHL). From 1981 to 1984, 34 patients with advanced drug resistant NHL were treated with SHD-LFI either to the whole abdomen (24 patients) or to the upper half body (10 patients). Overall, 19 of 23 patients achieved symptomatic improvement, while objective response was noted in 23 of 30 patients. We noted subjective and objective response in all histologies, and duration of response was not significantly different. Our results suggest a beneficial role for the early and judicious use of SHD-LFI in NHL.

Paraganglioma of the thyroid gland.

A case of a paraganglioma located within the thyroid gland is reported, and the light- and electron-microscopic features are described. Review of the literature reveals only one other case of intrathyroidal paraganglioma, which was associated with bilateral carotid body tumors. Regarding the present case, no similar tumors have been noted elsewhere. The findings support the view that the thyroid gland should be included among the unusual sites at which primary paragangliomas may occur.

Sexual strategies theory: an evolutionary perspective on human mating.

This article proposes a contextual-evolutionary theory of human mating strategies. Both men and women are hypothesized to have evolved distinct psychological mechanisms that underlie short-term and long-term strategies. Men and women confront different adaptive problems in short-term as opposed to long-term mating contexts. Consequently, different mate preferences become activated from their strategic repertoires. Nine key hypotheses and 22 predictions from Sexual Strategies Theory are outlined and tested empirically. Adaptive problems sensitive to context include sexual accessibility, fertility assessment, commitment seeking and avoidance, immediate and enduring resource procurement, paternity certainty, assessment of mate value, and parental investment. Discussion summarizes 6 additional sources of behavioral data, outlines adaptive problems common to both sexes, and suggests additional contexts likely to cause shifts in mating strategy.

Study of clonality in myelodysplastic syndromes: detection of trisomy 8 in bone marrow cell smears by fluorescence in situ hybridization.

The lineage involvement in myelodysplastic syndromes (MDS) is still unclear. To determine the clonality and the evolution of the disorder, a retrospective study on bone marrow smears from seven MDS patients with trisomy 8 was performed using fluorescence in situ hybridization (FISH). We observed that the trisomy of chromosome 8 was selectively expressed in the myeloid-derived cells. No mature lymphocytes or plasma cells expressed three signals. Our studies demonstrate here the value of FISH for identifying the affected cell lineage. Furthermore, the easy quantification of the abnormal cells can help in assessing the progression of the disease.

Usefulness and limitations of serum and urine lysozyme levels in the classification of acute myeloid leukemia: an analysis of 208 cases.

The revised French-American-British (FAB) classification system for acute myeloid leukemia (AML) recommends the determination of serum lysozyme (SL) or urine lysozyme (UL) levels as an aid in distinguishing acute myeloblastic leukemia with maturation (FAB M2) from acute myelomonocytic leukemia (M4). We reviewed retrospectively 208 cases of adult leukemia in which SL and/or UL were obtained. Elevated lysozyme levels were not found in any of the M0, M3, or M7 cases, but were increased (false positive) in three (14%) M1 cases, 18 (19%) M2 cases and one (20%) M6 case. Although a UL value in excess of 3x normal was found in most cases of AML M4 and M5, only five (11%) M4 cases and three (20%) M5 cases had SL elevations of this magnitude. Lysozyme levels need to be interpreted in conjunction with other parameters for FAB classification.

Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine.

BACKGROUND: Transdermal nicotine is of value in active ulcerative colitis but causes adverse events because of systemic absorption. Nicotine enemas may give rise to fewer adverse events. AIM: To assess the pharmacokinetics of nicotine enemas in three doses. METHODS: Thirteen volunteers, all non-smokers but three ex-smokers, were given enemas on separate occasions containing 3, 6 and 9 mg of nicotine, in ascending dose order. Adverse events were recorded and blood samples taken over 8 h for measurement of serum nicotine and cotinine. RESULTS: Enemas were retained by most subjects. Eleven of 14 adverse events were 'early'--30-105 min after the enema, corresponding to maximum plasma nicotine concentrations; three events were later, 4-8 h after the enema and unrelated to the tmax. 'Early' adverse events occurred in eight subjects--six with 9 mg. The three highest plasma nicotine concentrations were with 9 mg and associated with headache, nausea and sweating. Only one had adverse events with 3 mg and withdrew from the study. Nicotine Cmax with 6 and 9 mg doses were respectively two and three times the value with 3 mg. Peak nicotine concentrations occurred 44-50 min after the enema. CONCLUSION: The 6 mg dose of nicotine probably represents the dose to use in clinical practice - for the highest therapeutic dose with a low risk of adverse events.

Molecular comparisons of the Culex pipiens (L.) complex esterase gene amplicons.

The amplification of carboxylesterase genes is a mechanism of organophosphate resistance in Culex mosquitoes. Amplified carboxylesterase genes from an insecticide resistant Culex pipiens strain collected in Cyprus were analysed and compared to other Culex amplified carboxylesterase alleles. A 12 kb section of genomic DNA containing two gene loci coding for carboxylesterase alleles A5 and B5 was cloned and sequenced. A comparison between this amplicon and one from a strain with co-amplified carboxylesterase alleles A2 and B2 revealed a number of differences. The intergenic spacer was 3.7 kb in length in the A5-B5 amplicon (2.7 kb in A2-B2) and contained putative Juan and transposable elements upstream of B5. A fragment of a gene with high homology to aldehyde oxidase was also present immediately downstream of A5. The comparison revealed no differences that would explain the successful spread of the A2-B2 amplicon worldwide whilst the A5-B5 amplicon is restricted to the Mediterranean.

Chronic relapsing polyneuropathy associated with immunoblastic lymphadenopathy.

Two episodes of severe, relapsing sensorimotor polyneuropathy closely paralleled the course of systemic illness in a patient with immunoblastic lymphadenopathy. A review of the literature shows three other cases, although none with documented pathologic changes in muscles and nerves. Based on the pathologic findings in this patient, the peripheral neuropathy associated with immunoblastic lymphadenopathy can be classified under the group of relapsing inflammatory polyneuropathies associated with systemic disorders. Whether prednisone therapy helped this condition is uncertain.

Prolonged perfusion with a membrane oxygenator in awake ponies.

Prolonged extracorporeal membrane oxygenation (PEMO) was performed in 6 adult ponies with the membrane oxygenator in vein-to-artery bypass circuit. A flow rate equal to 46 per cent of control cardiac output was diverted through the PEMO circuit of 10 to 24 hours. Three of the 6 ponies were perfused for at least 20 hours and developed no complications. Immediately following initiation of PEMO, left ventricular output decreased; however, in the interval between 6 and 24 hours, left ventricular output was increased above control levels. Aortic pressure and left ventricular work were markedly elevated during PEMO. Pulmonary ventilation and oxygen uptake also decreased initially but were elevated during later stages of bypass. Pulmonary compliance did not change, except in those studies in which problems were encountered with perfusion techniques. Hepatic glycolysis and hyperglycemia occurred and were more severe in ponies with catheter-produced thrombi. Marked diuresis, which could be attributed only partially to the hyperglycemia, was present throughout PEMO. Based on the minimal morphologic changes observed in the ponies, extracorporeal circulation diverting one half of the cardiac output through a membrane oxygenator can be safely performed for up to 24 hours.