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PubMed2006

Pollution biomarkers in estuarine animals: critical review and new perspectives.

In this review, recent developments in monitoring toxicological responses in estuarine animals are analyzed, considering the biomarker responses to different classes of pollutants. The estuarine environment imposes stressful conditions to the organisms that inhabit it, and this situation can alter their sensitivity to many pollutants. The specificity of some biomarkers like metallothionein tissue concentration is discussed in virtue of its dependence on salinity, which is highly variable in estuaries. Examples of cholinesterase activity measurements are also provided and criteria to select sensitive enzymes to detect pesticides and toxins are discussed. Regarding non-specific biomarkers, toxic responses in terms of antioxidant defenses and/or oxidative damage are also considered in this review, focusing on invertebrate species. In addition, the presence of an antioxidant gradient along the body of the estuarine polychaete Laeonereis acuta (Nereididae) and its relationship to different strategies, which deal with the generation of oxidative stress, is reviewed. Also, unusual antioxidant defenses against environmental pro-oxidants are discussed, including the mucus secreted by L. acuta. Disruption of osmoregulation by pollutants is of paramount importance in several estuarine species. In some cases such as in the estuarine crab Chasmagnathus granulatus, there is a trade off between bioavailability of toxicants (e.g. metals) and their interaction with key enzymes such as Na(+)-K(+)-ATPase and carbonic anhydrase. Thus, the metal effect on osmoregulation is also discussed in the present review. Finally, field case studies with fish species like the croaker Micropogonias furnieri (Scianidae) are used to illustrate the application of DNA damage and immunosuppressive responses as potential biomarkers of complex mixture of pollutants.

Animals↗
PubMed2002

Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential.

A central development of the past decade has been in our understanding of the interactions between, and interdependence of, the innate and adaptive immune responses. Innate immunity recognizes 'danger' signals and activates adaptive immunity in a targeted, appropriate and effective response. Dendritic cells and macrophages have a central role in this process, and pharmacological agents that modulate the functions of these cells could have therapeutic value. The imidazoquinolone compounds, of which imiquimod, formulated as Aldara trade mark, is the best characterized to date, are such molecules. Imiquimod and its homologues act by activating macrophages and other cells via binding to cell surface receptors, such as Toll receptor 7, thereby inducing secretion of pro-inflammatory cytokines, predominantly interferon (IFN)-alpha, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. This locally generated cytokine milieu biases towards a Th1 cell mediated immune response with the generation of cytotoxic effectors, and this has been exploited clinically in the treatment of viral infections (human papillomavirus, herpes simplex virus, molluscum contagiosum) and nonmelanoma skin cancer. Imiquimod has been shown to be significantly more effective than placebo in clearing genital warts, and mechanism of action studies indicate that this is related to the ability to generate proinflammatory cytokines and a Th1 response. Intra-epithelial neoplasms of cutaneous and mucosal surfaces are associated with human papillomavirus infection and there is some evidence that immune response modifiers may have therapeutic value for these lesions. Topical immunotherapy with immunomodulators shows potential for effective and patient-friendly treatment of cutaneous viral infections. These compounds also have adjuvant properties that could significantly enhance conventional vaccine strategies.

Adjuvants, Immunologic↗
PubMed2000

Rewriting the regulations: how the World Trade Organisation could accelerate privatisation in health-care systems.

The World Trade Organisation (WTO) is drawing up regulatory proposals which could force governments to open up their public services to foreign Investors and markets. As part of the General Agreement on Trade in Services (GATS) negotiations, the WTO working party on reform of domestic regulation is developing a regulatory reform agenda which could mark a new era of compulsion in international trade law. Article VI.4 of the GATS is being strengthened with the aim of requiring member states to show that they are employing least trade-restrictive policies. The legal tests under consideration would outlaw the use of non-market mechanisms such as cross-subsidisation, universal risk pooling, solidarity, and public accountability in the design, funding, and delivery of public services as being anti-competitive and restrictive to trade. The domestic policies of national governments will be subject to WTO rules, and if declared illegal, could lead to trade sanctions under the WTO disputes panel process. The USA and European Union, with the backing of their own multinational corporations, believe that these new powers will advantage their own economies. Health-care professionals and public-health activists must ensure that this secretive regulatory reform process is opened up for public debate.

Delivery of Health Care↗
PubMedDate not supplied

Ancient origins of human developmental plasticity.

Animals have the ability to alter development, physiology, growth, and behavior in response to different environmental conditions. These responses represent critical assessments of both external and internal factors. For example, the timing of metamorphosis, hatching, or birth depends on the trade-offs between growth opportunity and mortality risk in the developmental habitat. Physiological sensors compute these trade-offs as a function of energy balance and environmental stress, and effectors initiate physiological, developmental, and behavioral responses to these determinations. The neuroendocrine stress axis provides a means for animals to integrate information from multiple sources and to respond accordingly. Considerable evidence now supports the view that the secretion of hormones critical to development (corticosteroid and thyroid hormones) is controlled by a common neuroendocrine stress pathway involving corticotropin-releasing factor (CRF) and related peptides. CRF produced in the hypothalamus stimulates the biosynthesis and secretion of both thyroid and corticosteroid hormones, leading to accelerated tadpole metamorphosis. Similarly, in mammals CRF of fetal and placental origin has been shown to influence the timing of birth. Studies in several experimental animal models and in humans show that early life experience can have long-term phenotypic consequences. Furthermore, there is evidence that phenotypic expression is strongly influenced by the actions of stress hormones produced during development. The integrated neuroendocrine response to stress, and its role in timing critical life history transitions and establishing long-term phenotypic expression, arose early in the evolution of vertebrates.

Adaptation, Physiological↗
PubMed2004

FDA-preapproved drugs targeted to the translational regulation and processing of the amyloid precursor protein.

The 5' untranslated region (5'UTR) of the transcript encoding the Alzheimer's amyloid precursor protein (APP) is a key regulatory sequence that determines the amount of intracellular APP holoprotein present in brain derived cells. Using neuroblastoma cells (SY5Y) we developed a transfection based screen of a library of FDA drugs to identify compounds that limited APP luciferase reporter expression translated from the APP 5'UTR. Paroxetine (Paxil trade mark ), dimercaptopropanol, phenserine, desferrioxamine, tetrathiolmobdylate, and azithromycin were six leads that were subsequently found to also suppress APP holoprotein levels or to alter APP cleavage (azithromycin). Since APP holoprotein levels are proportionate to Abeta peptide output in many systems we tested the efficacy of paroxetine and dimercaptopropanol to limit Abeta secretion as measured by ELISA assays. Paroxetine and dimercaptopropanol limited Abeta peptide secretion from lens epithelial cells (B3 cells). Interestingly, paroxetine changed the steady-state levels of transferrin receptor mRNAs. These data suggested that this serotonin reuptake inhibitor (SSRI) provided extra pharmacological action to chelate interacellular iron or change the intracellular iron distribution. An altered iron distribution would be predicted to indirectly limit APP holoprotein expression and Abeta peptide secretion.

5' Untranslated Regions↗
PubMed1984

[Clinical experiences with a new gel-like wound dressing after skin transplantation].

Free split skin grafting is now widely practised on a routine basis in accident surgery. All conventional wound dressing methods have considerable drawbacks, and this is one of the reasons why successful skin grafting is still an unsafe procedure even under the very best of conditions and quite often resembles an experiment more than a scientific procedure, with an unpredictable outcome. Today, however, we can command over a wound dressing, using the polyacrylamide agar hydrogel developed by the Max Planck Institute of Immunobiology at Freiburg and which is being marketed under the trade name of Geliperm. This dressing can maintain the physiological wound environment during the first few critical days following grafting; it enables conditioning of the wound; it protects the wound against bacterial invasion and prevents drying-out of the graft and the base of the wound; and it is capable of absorbing wound secretion to a certain degree. Healing chances of the graft can be considerably improved by the use of Geliperm. Thanks to its high measure of elasticity it can adapt itself to the wound surface without sticking to it. The transparent nature of the material enables to observe and assess the healing processes at any time and to recognize possible complications during healing. Failures are almost always due to prolonged deposition of the gel plates, but this can be safely avoided by regularly changing the deposit. Deposits inadvertently left for too long, so that they have started drying at the wound surface, can be detached without any trouble and painlessly without any risk of damaging the graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylamides↗
PubMed2003

Weighed in the balance? The corporation of apothecaries in Bordeaux, 1690-1790.

Based on a collective biography of apothecaries, surgeons, and physicians in Bordeaux between 1690 and 1790, this article offers a counterbalance to the prevailing view of apothecaries. It suggests that, although numbers may have been falling and corporations failing elsewhere in France, the favourable situation of Bordeaux aided the survival of the corporation of apothecaries in that city. It suggests that apothecaries were important in providing a wide range of goods and services to patients, and traces their involvement in retail, wholesale, and international trade. Control of numbers is shown to be linked to a desire to exploit their monopoly of the market, which led to increases in wealth for individual practitioners. A change in traditional inheritance strategies is linked to a new emphasis on merit, and to knowledge obtained through training outside the confines of the apprenticeship system. The 'secrets of the craft' are seen to be undermined by the public nature of the emerging science of chemistry. The corporation of apothecaries in Bordeaux was transformed through its absorption of three new types of practitioner-entrepreneurs, pharmacists, and scientists-yet it survived due to the substantial and continuing presence of traditional, locally born, and locally trained apothecaries.

France↗
PubMed2002

The contentious nature of gestational diabetes: diet, insulin, glyburide and metformin.

Gestational diabetes (GD) develops because pregnancy increases requirements for insulin secretion while increasing insulin resistance. Women with GD often have impaired pancreatic beta-cell compensation for insulin resistance. The nature of GD is currently contentious, with debate about its existence, diagnosis and ramifications for both mother and offspring from pregnancy into later life. Also contentious are the outcomes of intervention with diet, insulin, glyburide (Glynase trade mark, Pharmacia Upjohn) and metformin (Glucophage trade mark, Bristol-Myers Squibb). There is consensus that women with unequivocal GD have a significant risk of adverse perinatal outcomes and increased risk of later type 2 diabetes mellitus. Foetuses from pregnancies with GD have a higher risk of macrosomia (associated with higher rate of birth injuries), asphyxia, and neonatal hypoglycaemia and hyperinsulinaemia. Uncontrolled GD predisposes foetuses to accelerated, excessive fat accumulation, insulin resistance, pancreatic exhaustion secondary to prenatal hyperglycaemia and possible higher risk of child and adult obesity and type 2 diabetes mellitus later in adult life. However, there is no consensus as to whether glucose intolerance of a severity below unequivocal GD is related to adverse maternal, fetal or perinatal outcomes, and whether this relationship is a continuous one. If dietary intervention is not sufficient in the treatment of GD, then, historically, insulin has been added. Recent studies suggest that glyburide may be efficaciously substituted for insulin. Preliminary studies suggest that metformin may have the unique potential to prevent the development of GD.

Clinical Trials as Topic↗
PubMed2000

Sozodont powder dentifrice and Mrs. Winslow's Soothing Syrup: dental nostrums.

The Great Patent Medicine Era (1865-1907) was the golden age of secret remedies--quack, non-prescription medicinal products, sold over-the-counter. Making outrageous and unsubstantiated claims, the makers of dental nostrums purported to effectively treat stained teeth, bad breath, diseased gums, toothache and teething discomfort. No proof was required to substantiate the safety and effectiveness of these concoctions. Advertisements for patent medicines were widespread, appearing in newspapers, almanacs, magazines, trade cards and multiple other media forms. Many dental patent medicines contained acids, abrasive substances, alcohol and/or narcotics, such as heroin, cocaine and morphine. Sozodont Tooth Powder, the most widely promoted and successful dentifrice of this era, claimed to "harden and invigorate the gums, purify and perfume the breath and beautify and preserve the teeth from youth to old age." Early dental researchers found that this remedy contained harsh ingredients (such as acid, sharp abrasives and astringents) which could destroy tooth substance. Mrs. Winslow's Soothing Syrup, an extremely popular dental nostrum, was intended to quiet a fretful child during the teething process. However, it contained generous levels of alcohol and morphine sulfate which could cause coma, addiction or death in an infant. Although somewhat chemically altered, these two products were eventually removed from the market in the 1930s.

Analgesics, Opioid↗
PubMed1995

The steroidogenic and morphological effects of paclitaxel on cultured ovarian cancer cells.

We have studied the biochemical effects of paclitaxel (trade name Taxol) in three ovarian cancer (OV Ca) cell lines and JEG-3 choriocarcinoma cells. Paclitaxel (1 microgram/ml) was cytotoxic to approximately 80% of OV Ca cells, and the ED50 ranged from 6 to 9 ng/ml. Paclitaxel was also cytotoxic to JEG-3 cells (ED50 40 ng/ml), but even at 1 microgram/ml, 40-50% of the cells survived paclitaxel treatment. Paclitaxel increased 17 beta-estradiol secretion 3-4 fold in all three OV Ca cell lines with an ED50 range of 3-13 ng/ml. Similarly, paclitaxel increased estradiol secretion from JEG cells with an ED50 of 50 ng/ml. Colchicine also increased estradiol secretion significantly from OV Ca cells at 2 microM while reducing cell number approximately 40% (beta-lumicolchicine, an inactive isomer, was ineffective at this concentration). Paclitaxel (1 microgram/ml) treatment of BR OV Ca cells produced alterations in morphology leading to "rounding" of cells within 6 h of treatment. Simultaneously, paclitaxel increased immunohistochemical staining for aromatase, and this increase was coincident with morphological alterations. The present results demonstrate that low concentrations of paclitaxel can have significant steroidogenic, as well as cytotoxic, effects on OV Ca cells, suggesting that paclitaxel may activate signal transduction pathways in addition to disrupting microtubule function. These findings further suggest that paclitaxel could be efficacious at submicromolar concentrations.

Adenocarcinoma↗
PubMed2006

Genome sequence of Aeromonas hydrophila ATCC 7966T: jack of all trades.

The complete genome of Aeromonas hydrophila ATCC 7966(T) was sequenced. Aeromonas, a ubiquitous waterborne bacterium, has been placed by the Environmental Protection Agency on the Contaminant Candidate List because of its potential to cause human disease. The 4.7-Mb genome of this emerging pathogen shows a physiologically adroit organism with broad metabolic capabilities and considerable virulence potential. A large array of virulence genes, including some identified in clinical isolates of Aeromonas spp. or Vibrio spp., may confer upon this organism the ability to infect a wide range of hosts. However, two recognized virulence markers, a type III secretion system and a lateral flagellum, that are reported in other A. hydrophila strains are not identified in the sequenced isolate, ATCC 7966(T). Given the ubiquity and free-living lifestyle of this organism, there is relatively little evidence of fluidity in terms of mobile elements in the genome of this particular strain. Notable aspects of the metabolic repertoire of A. hydrophila include dissimilatory sulfate reduction and resistance mechanisms (such as thiopurine reductase, arsenate reductase, and phosphonate degradation enzymes) against toxic compounds encountered in polluted waters. These enzymes may have bioremediative as well as industrial potential. Thus, the A. hydrophila genome sequence provides valuable insights into its ability to flourish in both aquatic and host environments.

Aeromonas hydrophila↗
PubMed2006

Positive selection of the Hrp pilin HrpE of the plant pathogen Xanthomonas.

The plant-pathogenic bacterium Xanthomonas campestris pv. vesicatoria possesses a type III secretion (TTS) system which is encoded by the 23-kb hrp (hypersensitive response and pathogenicity) gene cluster. The TTS system is necessary for pathogenicity in susceptible hosts and induction of the hypersensitive response in resistant plants. At the cell surface, the TTS system is associated with an extracellular filamentous structure, the Hrp pilus, which serves as a conduit for the transfer of bacterial proteins into the plant cell cytosol. The major pilus component, the HrpE pilin, is unique to xanthomonads. Previous work showed that HrpE contains two regions: a hypervariable surface-exposed domain, including the N-terminal secretion signal, and a C-terminal polymerization domain. In this study, the evolutionary rate of the hrpE gene was analyzed. Twenty-one alleles were cloned, sequenced, and compared with five known hrpE alleles. The ratio of synonymous (K(s)) and nonsynonymous (K(a)) substitution rates shows that parts of the HrpE N terminus are subjected to positive selection and the C terminus is subjected to purifying selection. The trade-off between positive and purifying selection at the very-N terminus allowed us to ascertain the amphipathic alpha-helical nature of the TTS signal. This is the first report of a surface structure from a plant-pathogenic bacterium that evolved under the constraint of positive selection and hints to the evolutionary adaptation of this extracellular appendage to avoid recognition by the plant defense surveillance system.

Adaptation, Physiological↗
PubMed2004

Comparison of the LMA-ProSeal and LMA-Classic in children.

BACKGROUND: The LMA-ProSeal is a new laryngeal mask airway with a rear cuff and drainage tube that allows a higher seal pressure than the LMA-Classic for the same intra-cuff pressure, and it permits drainage of gastric secretions and access to the alimentary tract. The LMA-ProSeal can be used in children but it does not have a rear cuff. This study compared the LMA-ProSeal and the LMA-Classic in children for ease of insertion, airway sealing pressure and fibre-optic visualization. METHODS: Sixty ASA I-II children undergoing herniorrhaphy, orchiopexy or myringotomy were included. The patients were randomly assigned to size 2 LMA-Classic trade mark or size 2 LMA-ProSeal groups for airway management. We assessed success rates at first attempt of insertion, airway sealing pressure, fibre-optic position, success rates of gastric tube placement and postoperative blood staining of the device, tongue-lip-dental trauma and hoarseness. RESULTS: There was no statistical difference between the two groups for the success rates at first attempt of insertion, airway sealing pressure and fibre-optic position. Gastric tube insertion was successful in 90% of cases in the LMA-ProSeal group. The LMA-Classic had a higher rate of postoperative blood staining, but there was no tongue-lip-dental trauma or hoarseness in either group. CONCLUSION: We conclude that ease of insertion and airway sealing pressure are similar between the LMA-ProSeal and the LMA-Classic in children.

Anesthesia, Inhalation↗
PubMed2002

Renal vein renin measurements accurately identify renovascular hypertension caused by total occlusion of the renal artery.

OBJECTIVE: To assess the usefulness of indexes derived from renal vein renin measurements. DESIGN: A 12-year prospective study. SETTING: A tertiary institutional referral centre. PATIENTS AND METHODS: Between 1988 and 2000, we studied 152 consecutive hypertensive patients with a high pre-test probability of renovascular hypertension (RVH). RVH was diagnosed retrospectively on the basis of reduction in blood pressure after correction of ischaemia at follow-up. Renal vein renin measurements were used to calculate the ratios: Visch/Vctl (renal vein renin ratio; RVRR); Vctl/Viivc; (Visch - Viivc)/Viivc; (Vctl - Viivc)/Viivc, where Visch and Vctl indicate plasma renin activity (PRA) in the ischaemic and contralateral renal veins, respectively, and Viivc denotes PRA in the infrarenal inferior vena cava. A receiver operator characteristics (ROC) curve analysis was used to determine the cut-off value of renal vein renin measurement indexes that provided the best discrimination between patients with and without RVH and to identify patients with RVH caused by total occlusion of the renal artery. RESULTS: Sixty-seven patients were diagnosed as having RVH: 51 had significant renal artery stenoses (RVH non-occluded) and 16 had total renal artery occlusion (RVH occluded). Of the remaining 85 patients in whom RVH was excluded (non-RVH group), 27 had reno-parenchymal hypertension and 58 had essential hypertension. Of the renal vein renin measurement indexes, only RVRR and (Visch - Viivc)/Viivc in RVH-occluded patients differed significantly (P < 0.005) from those in the non-RVH group and showed the best performance by ROC curve analysis. This analysis also showed that, at any cut-off value, RVRR was far more accurate for identification of RVH-occluded patients than for identification of RVH non-occluded patients, both in the subgroup with unilateral and, even more so, in those with bilateral renal artery lesions. The best trade-off between sensitivity and false-positive rate was provided by cut-off values of 1.55 and 1.70 of the RVRR for identification of non-occluded and occluded RVH, respectively. CONCLUSIONS: RVRR is more useful for establishing an indication for nephrectomy in patients with renal artery occlusion than for identifying those patients with renal artery stenosis who will benefit from revascularization. In patients with RVH with bilateral renal artery lesions, lateralization of renin secretion occurs only in the presence of total renal artery occlusion. Different cut-off values are necessary for identification of non-occluded and occluded RVH.

Adolescent↗
PubMed2002

Trade-offs in group living: transmission and disease resistance in leaf-cutting ants.

Sociality can be associated with significant costs due to the increased risk of disease transmission. However, in some organisms the costs may be offset by benefits due to improvements in defences against parasites. To examine this possible trade-off between infection risk and disease resistance, we used Acromyrmex leaf-cutting ants and the entomopathogenic fungus Metarhizium anisopliae as the model system. Ants exposed to the parasite were found to have substantially improved survival when they were kept with nest-mates, while the cost of being in a group in terms of increased disease transmission was very low. The efficiency of transmission is described by the transmission parameter, which decreased with increasing host density showing that transmission rates are inversely density dependent. Both grooming and antibiotic secretions appeared to be important in resistance against the parasite, with the defences of small workers being particularly effective. The results indicate that leaf-cutting ant colonies may have much greater resistance to disease than would be predicted from the high densities of host individuals within them. Unlike most organisms, group living in these ants may actually be associated with a net benefit in terms of disease dynamics.

Animals↗
PubMed2002

Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload. Role of gastric acid secretion.

In normal subjects, the gastric ionisation of calcium and phosphate seems to be a prerequisite for their intestinal absorption. We investigated the behavior of the plasma calcium and phosphate profile in 30 patients on regular dialysis treatment in the 6 h following a meal containing 1 g of calcium and 2 g of phosphate. Moreover, to assess the role of gastric acidity, the study was repeated after 3 days on omeprazole administration, to nearly abolish gastric acid secretion. Both total plasma calcium and ionized calcium peaked after the meal (at 30 and 120 min, respectively) only in basal study, while no peak was observed after the administration of omeprazole. Surprisingly, both in basal and in the omeprazole study the levels of plasma phosphate did not increase after the test meal. In conclusion, as in normal subjects, the gastric ionization of dietary calcium promotes the intestinal absorption of calcium in uremic patients on dialysis treatment, while the acute gastric acid inhibition by omeprazole reduced the intestinal calcium transport. In contrast, with the "trade off" hypothesis we did not observe any postprandial phosphate peak after the dietary load, and, in contrast with normal subjects, omeprazole administration did not influence the phosphate profile.

Adult↗
PubMed2000

Pollen viability reduction as a potential cost of ant association for Acacia constricta (Fabaceae).

Field studies investigating the impact of ants on the reproduction of plants bearing extrafloral nectaries have traditionally focused on seed production, a component of female fitness. The purpose of this study was to test whether ants can affect the pollen viability, a component of male fitness, when they visit flowers of the shrub Acacia constricta. Acacia constricta inflorescences hand-pollinated with flowers over which Formica perpilosa ants had crawled set significantly fewer seed pods than inflorescences hand-pollinated by control flowers that had no contact with ants. Many ant species secrete antibiotic substances onto the integument that render pollen inviable, and these secretions are probably the mechanism for reduced pollen viability in this study. The ratio of seed pods produced by self-pollinated inflorescences to those produced by cross-pollinated inflorescences was 0.16, indicating that A. constricta is largely self-incompatible. Because F. perpilosa workers forage primarily on the acacia tree under which they nest, they are unlikely to serve as efficient vectors of outcrossing. Previous work showed that A. constricta shrubs with F. perpilosa ants produce approximately twice as many seeds as similarly sized plants not so associated. The results indicate that association with F. perpilosa could cause a reproductive trade-off for A. constricta: benefits to female function may be accompanied by costs to male function. Selection to discourage ant visitation to flowers may have affected the pollination biology of this and other ant-associated plant species.

Journal Article↗