Efficacy and Safety of Tranexamic Acid for the Control of Surgical Bleeding in Patients Under Liposuction.

Liposuction remains one of the most frequently performed cosmetic surgical procedures and its popularity is increasing every year. However, since its inception, justified concerns regarding patient safety have placed limits on the volume of fat that can be aspirated, influenced by hemodynamic fluctuations and blood loss during liposuction. Tranexamic acid (TXA) is an antifibrinolytic agent that competitively inhibits the conversion of plasminogen to plasmin, thus preventing the binding and degradation of fibrin. Despite the existence of evidence of the effectiveness of TXA in orthopedic and cardiac surgeries, there is little evidence of its use in liposuction. The objective of this study was to evaluate the efficacy and safety of tranexamic acid in the control of surgical bleeding in patients undergoing liposuction, through a prospective, open, randomized and controlled clinical trial. Two groups of 25 participants each were formed to whom the application of TXA in a tumescent solution prior to liposuction or liposuction with the traditional technique was randomly assigned. The results showed a decrease in blood loss reflected by the differences in the final hematocrit values, as well as decrease in the same per aspirated volume (p = 0.003). No adverse events were found related with the TXA application and no blood transfusions were required in this group, in contrast to the control group where the need for blood transfusion was present in 20% of the intervened participants. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Asthma and paracetamol: could we really know what happens between them?

An association between paracetamol use or exposure in different times of life, including gestation and childhood, and asthma has been observed in recent years. Causality cannot be established from observational studies because of the arguable presence of many confounding factors and biases. Randomised trials are needed to disclose the nature of the association, but are difficult to carry out because of ethic, economic and logistical issues as large patient samples should be involved for a long time in such studies. Pragmatic trials may be the best option to shed some light on this issue. Questions regarding the problems and difficulties of conducting such trials and the way to overcome them are discussed.

Solubilization and Controlled Release Strategy of Poorly Water-Soluble Drugs.

The processes of solubilization and controlled release of drugs that are poorly soluble in water are highly relevant in drug preformulation studies in pharmaceutical development [...].

Relationship between surface dissolved iron inventories and net community production during a marine heatwave in the subarctic northeast Pacific.

From winter 2013-14 to the end of 2015-16, a high pressure atmospheric system induced elevated sea surface temperatures in the offshore subarctic northeast Pacific, resulting in a marine heatwave. Increased stratification due to the heatwave resulted in shoaling of the winter mixed layer and a decrease in nutrient re-supply to the euphotic zone. Here, we investigate relationships between dissolved iron (dFe) and macronutrients, net community production (NCP), (micro)nutrient uptake ratios, and phytoplankton community composition in the winter and summer from 2012 to 2015 to gain insight into coupled biogeochemical responses to the heatwave. Our investigation highlights the importance of external dFe supply during marine heatwave events, as a more shallow mixed layer reduces the transport of essential (micro)macronutrients to the surface layer. We conclude that recycled dFe did not contribute to NCP in 2014, but rather the vertical displacement of dFe rich water unrelated to mixed layer deepening played a major role. In 2015, such transport was not detected, resulting in abnormally low dFe and shift toward higher biomass of pico- and nano-phytoplankton size-classes.

Titanium release in serum of patients with different bone fixation implants and its interaction with serum biomolecules at physiological levels.

Increased concentrations of circulating metal-degradation products derived from the use of Ti orthopaedic implants may have deleterious biological effects over the long term. Therefore, there is an increasing need to establish the basal level of Ti in the serum of the population (exposed and non-exposed) with appropriate highly sensitive techniques and strategies. With this aim, we have developed a quantitative strategy for the determination of total Ti concentration in human serum samples by isotope dilution analysis using a double-focussing inductively coupled plasma mass spectrometer. Minimizing sample handling and therefore contamination issues, we obtained detection limits of about 0.05 µg L(-1) Ti working at medium resolution (m/Δm 4000). Such extremely good sensitivity permitted us to establish the range of Ti concentration in serum of 40 control individuals (mean 0.26 µg L(-1)) and also to compare it with the level in exposed patients with different Ti metal implants. On the other hand, Ti transport "in vivo" studies have been enabled by online coupling of liquid chromatography (anion-exchange) separation and double-focussing inductively coupled plasma mass spectrometry for sensitive detection of Ti. The development of a postcolumn isotope dilution strategy permitted quantitative characterization of the Ti-transporting biomolecules in human serum. The results for unspiked serum revealed that 99.8% of the Ti present in this fluid is bound to the protein transferrin, with column recoveries greater than 95%.

Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk.

BACKGROUND AND AIMS: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. METHODS AND RESULTS: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin-Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100 g of F&V (Beta=0.150;P<0.001) had a greater contribution to TPE than 100 mL of coffee (Beta=0.141;P=0.001), and the latter two foods contributed more than the consumption of 100 mL of wine (Beta=0.120;P=0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio=0.64; 95% confidence interval 0.45 to 0.92; P=0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P=0.024 and P=0.003, respectively). CONCLUSIONS: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements.

Colloidal and polymeric contributions to the yielding of dense microgel suspensions.

HYPOTHESIS: Soft microgel colloids can be densely packed since particle networks can compress and interpenetrate. This evolution of the particle's internal structure associated with packing is expected to determine the linear viscoelastic properties and the yielding behavior of dense suspensions of microgel colloids. EXPERIMENTS: We investigated the volume fraction-dependent linear and non-linear rheological response of suspensions of soft core-shell particles formed by a poly(N-isopropylacrylamide) (PNIPAM) microgel core and a thin poly(ethylene glycol) (PEG) shell. FINDINGS: The linear viscoelasticity of suspensions reveals a transition from a fluid to a jammed glass state. Increasing volume fraction within the jammed state, the linear storage modulus and the yield stress show distinct regimes associated with the evolution of particle contacts, which involve progressive compression and interpenetration of the shell and core. The yielding of jammed suspensions occurs in two-steps: At small strains jammed cages are rearranged, while full disentanglement of interpenetrating networks only occurs at large deformations and results in fluidization. Yield strains and stresses increase with increasing shear rate or frequency, suggesting a progressive dominance of the timescale associated with shear over that associated with the internal dynamics of the system.

Randomized, crossover, single-blind, placebo-controlled, human pharmacology clinical trial with desoxypeganine, a new cholinesterase and selective MAO-A inhibitor: multiple-dose pharmacokinetics.

UNLABELLED: Desoxypeganine, a naturally occurring alkaloid, is being developed for its potential utility in the pharmacological treatment of alcohol abuse to reduce craving and depression in alcohol abusers, and might also be useful as a smoking cessation aid. During the preclinical development it was characterized as a cholinesterase inhibitor, acting preferentially on butyrylcholinesterase, and as a selective inhibitor of monoamine oxidase A but not monoamine oxidase B. OBJECTIVE: The aim of the present human pharmacology clinical trial was to assess the oral bioavailability, pharmacokinetic profile and tolerability of desoxypeganine, administered in a multiple-dose regimen to healthy volunteers. SUBJECTS AND METHODS: Eighteen healthy adult volunteers of both sexes received placebo, 50 mg and 100 mg desoxypeganine (b.i.d. for 3 days) in a single-blind, crossover, randomized manner. Main pharmacokinetic parameters after single and multiple doses were estimated. Clinical tolerability and clinical laboratory safety, including effect on QTc interval, were assessed. RESULTS: Non-compartmental estimations of Cmax, AUC, tmax, t1/2 and MRT at 12-h intervals are given. No significant dose effect was observed in tmax, t1/2 and MRT. Cmax and AUC are approximately double with the dose of 100 mg comparing with the dose of 50 mg. A significant increase (p < 0.05) on Cmax and AUC was also obtained with the highest dose administered in comparison with the lowest one, revealing a slight but clinically insignificant accumulation. Steady state of drug concentration was reached in both genders during the study period. Plasma protein binding of desoxypeganine amounted to approximately 18%. No severe adverse events were recorded and none of the subjects suffered from any adverse event that led to withdrawal from the study. Most frequently recorded adverse event was dizziness. No significant effects of desoxypeganine on vital signs, laboratory parameters or QTc interval were observed. CONCLUSIONS: The present clinical trial describes the pharmacokinetic profile of two doses of desoxypeganine, administered orally in multiple dose to healthy volunteers. The drug was well tolerated without any severe clinical, clinical laboratory, or ECG adverse events being recorded.

Serological Detection of Citrus tristeza virus with Antibodies Developed to the Recombinant Coat Protein.

Antibodies specific for the recombinant coat protein (rCP) of the p25 gene of Citrus tristeza virus (CTV) were developed in goats and rabbits and further evaluated as a complete kit for the detection of the virus using healthy and CTV-infected tissue. The combination of goat T1 used as primary (coating) and rabbit C3 as intermediate (detecting) rCP antibodies reacted efficiently, with optical density at 405 nm (OD405) values between 0.250 and 2.000 with samples from an international collection of diverse CTV isolates. The CTV isolates tested cause a broad spectrum of disease syndromes in different citrus hosts. The OD405 values for healthy tissue were less than 0.100. Likewise, the combination of goat T1 and rabbit C3 rCP antibodies gave consistent results for CTV-positive and -negative sample discrimination when directly compared with the Central California Tristeza Eradication Agency (CCTEA) antibodies used for large-scale CTV detection and a commercially available CTV serological detection kit. The combination of goat T1 and rabbit C3 rCP antibodies showed its suitability for large-scale indexing with samples collected in commercial groves as part of the CCTEA's regular monitoring program. The evaluation included 41,195 samples from 301 commercial groves from districts 1, 2, and 3. In total, 26 trees (0.063%) were found to be CTV positive using the T1/C3 rCP antibody combination. Results of this research provide evidence that rCP antibodies can be efficiently used for both capturing and detecting CTV antigens in double-antibody sandwich indirect enzyme-linked immunosorbent assay.

Phase I clinical trial with desoxypeganine, a new cholinesterase and selective MAO-A inhibitor: tolerance and pharmacokinetics study of escalating single oral doses.

Desoxypeganine (DOP) is a natural alkaloid that has been characterized as a cholinesterase inhibitor and a selective inhibitor of monoamine oxidase A. DOP has been investigated for its potential utility in the pharmacological treatment of alcohol abuse and as a smoking cessation aid. The aim of this clinical trial was to evaluate the tolerance and single-dose pharmacokinetic profile of DOP in healthy human volunteers. The study was an open-label, dose-escalation, phase I clinical trial involving the administration of increasing single oral doses of DOP (50, 100, 150 and 200 mg). The study was conducted according to the Declaration of Helsinki and Good Clinical Practice. Eighteen healthy adult volunteers (8 males and 10 females, age ranging 20-30 years) were recruited. DOP was administered sequentially, escalating in single doses of 50, 100, 150 and 200 mg in four experimental sessions with a washout period of at least 1 week between them. Progress to the next dose was allowed only if the previous dose was tolerated. Pharmacokinetic parameters were determined using noncompartmental methods. Clinical and analytical safety was assessed throughout the study, and QTc intervals were measured at regular intervals. The main pharmacokinetic parameters and renal excretion are described. No serious adverse events were registered, and none of the subjects discontinued the study because of lack of tolerance. All the adverse events recorded were mild to moderate and increased with the dose. The ECG measurements revealed that even at a higher dose, the QTc interval remained below the safety threshold. In summary, this first phase I study indicates that DOP has linear and dose-proportional pharmacokinetics, satisfactory oral bioavailability and plasma half-life and renal excretion. Also, DOP has shown an adequate safety profile that allows the continuation of clinical development.

Canine conjunctivitis and blepharitis.

The eyelids and conjunctiva are immunologically active structures with an extensive presence of blood vessels, lymphatics, and immune cells. Several immune-mediated phenomena can involve these structures either in isolation or in association with systemic clinical features. Immune-mediated blepharoconjunctival diseases are divided into two main categories: primary autoimmune disease in which the disease results from an attack against self-antigens and secondary immune-mediated disease in which the disorder results from exogenous material inducing autoimmune disease. Such causes of secondary immune-mediated disease include infectious agents and drugs. This article reviews the most important autoimmune and immune-mediated eyelid and conjunctival disorders in dogs.

Scaling patterns of heart rate variability data.

Detrended fluctuation analysis (DFA) is becoming a widely used technique for exploring the structure of correlations in heart rate variability (HRV) data. This method provides a scaling or fractal exponent alpha(x) derived from the behaviour of the root-mean-square fluctuations along different time scales n. Rather than just finding a single exponent, covering either short (alpha(1)) or long range (alpha(2)), we recently suggested tracking the local evolution of alpha(x), as in this way scaling patterns (SP), which seem to provide more detailed characterizations of HRV data, are revealed. Here, we evaluate such potential advantage by classifying long-term data from 51 subjects in normal sinus rhythm and 29 congestive heart failure patients. Using the SP we achieved a significantly better classification of these data than using alpha(x), or the statistic pNN20, thereby confirming that the SP provide a useful assessment of the correlation structure in HRV data.

Solubility parameter of drugs for predicting the solubility profile type within a wide polarity range in solvent mixtures.

The solubility enhancement produced by two binary mixtures with a common cosolvent (ethanol-water and ethyl acetate-ethanol) was studied against the solubility parameter of the mixtures (delta1) to characterize different types of solubility profiles. Benzocaine, salicylic acid and acetanilide show a single peak in the least polar mixture (ethanol-ethyl acetate) at delta1=22.59, 21.70 and 20.91 MPa1/2, respectively. Phenacetin displays two solubility maxima, at delta1=25.71 (ethanol-water) and at delta1=23.30 (ethyl acetate-ethanol). Acetanilide shows an inflexion point in ethanol-water instead of a peak, and the sign of the slope does not vary when changing the cosolvent. The solubility profiles were compared to those obtained in dioxane-water, having a solubility parameter range similar to that covered with the common cosolvent system. All the drugs reach a maximum at about 90% dioxane (delta1=23 MPa1/2). A modification of the extended Hildebrand method is applicable for curves with a single maximum whereas a model including the Hildebrand solubility parameter delta1 and the acidic partial solubility parameter delta1a is required to calculate more complex solubility profiles (with inflexion point or two maxima). A single equation was able to fit the solubility curves of all drugs in the common cosolvent system. The polarity of the drug is related to the shape of the solubility profile against the solubility parameter delta1 of the solvent mixtures. The drugs with solubility parameters below 24 MPa1/2 display a single peak in ethanol-ethyl acetate. The drugs with delta2 values above 25 MPa1/2 show two maxima, one in each solvent mixture (ethanol-water and ethanol-ethyl acetate). The position of the maximum in ethanol-ethyl acetate shifts to larger polarity values (higher delta1 values) as the solubility parameter of the drug delta2 increases.

Variations of pharmacokinetics of drugs in patients with cirrhosis.

Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies. As a consequence, therapeutic decisions in these patients are usually complex and subject to uncertainties. In this article, we review the regulatory guidelines to study responses to drugs according to pharmacokinetic variability and the published information that is useful for guiding the dosage adjustment of frequently used drugs in patients with cirrhosis (antivirals, antibiotics, analgesics, etc.) to obtain the best risk-benefit ratio.

[Complicated pleural infection: Analysis of 2 consecutive cohorts managed with a different policy]. / Derrame paraneumónico complicado: análisis de 2 cohortes consecutivas tratadas con distinto criterio.

INTRODUCTION: The treatment of complicated pleural infection (CPI) is controversial. Clinical guidelines recommend drainage, but with the lowest grade of evidence. Recent reports have observed good outcomes with antibiotics alone. We retrospectively compared the outcomes in two consecutive cohorts treated with different policies: the first treated according to pleural fluid charactersitics (2005-2009, interventional-prone, group 1) and the second according to clinical assessment (2010-2013, conservative-prone, group 2). METHODS: The clinical records of all children treated for CPI in our hospital between 2005 and 2013 were thoroughly reviewed. Primary outcomes were the proportion of children drained and the length of hospital stay (LHS). RESULTS: One hundred and nine patients (64 group 1 and 45 group 2) were analyzed. A chest tube was placed in 83% of patients in group 1 and 47% in group 2 (P<0.001). The mean LHS was 11.4 days for patients in group 1 and 12.3 for patients in group 2 (P=0.45); no differences were observed in other outcomes. CONCLUSION: Our results add to few recent observations reporting good outcomes in many children treated with antibiotics alone and challenge the need to drain most children with CPI. Clinical trials are now needed to identify when a drainage procedure would be useful.

Incidence of neutropenia during treatment of bone-related infections with piperacillin-tazobactam.

Of 41 patients with bone-related infections who were treated for > or =10 days with piperacillin-tazobactam, 14 (34%) developed neutropenia. Cumulative doses of piperacillin administered to neutropenic patients were higher than those administered to nonneutropenic ones (330 vs. 237 g; P=.008), and an inverse correlation was detected between the absolute neutrophil count at the end of treatment and the cumulative dose of piperacillin (r=-0.47, P=.002). Moreover, the incidence of piperacillin-tazobactam-induced neutropenia increased with an increase in the cumulative dose of piperacillin: 0% of patients in the first quartile of cumulative piperacillin doses, 33.3% in the second quartile, 40% in the third quartile, and 66.7% in the fourth quartile.

Serological techniques for detection of citrus tristeza virus.

Citrus tristeza virus (CTV) is the most economically important virus disease of citrus. In the last ten years, remarkable progress has been achieved in the development and improvement of new serological methods for CTV detection so that serology has become a dependable tool for many research, extension and regulatory purposes worldwide. CTV-specific polyclonal antisera and monoclonal antibodies have been developed in different research laboratories and used extensively in a wide range of different studies. This review describes the diverse serological methods developed for CTV detection and analyzes the advantages, disadvantages, relative sensitivity, applications, and present status of each method.

Development of a dot-immunobinding assay for detection of citrus tristeza virus.

The dot-immunobinding assay (DIBA) was adapted for detection of citrus tristeza virus (CTV) and compared with DAS-ELISA and DAS-indirect ELISA. DIBA was easy to perform and as sensitive as either ELISA procedure for CTV diagnosis. The entire test could be performed in 2-3 h using polyclonal antibodies, with minimal laboratory equipment. Three different polyclonal antibodies gave a strong positive reaction with 12 selected CTV isolates; however, each serum had to be cross-absorbed with sap from healthy plants before use. The broad spectrum 3DF1 monoclonal antibody reacted with most of the CTV isolates. The MCA-13 strain-specific monoclonal antibody was specific for most severe CTV isolates. As blocking agents, 3% bovine serum albumin (BSA), 3% gelatin, 0.5% non-fat dry milk or 5% Triton X-100 gave an adequate white background on the nitrocellulose membranes and permitted discrimination between infected and healthy samples. However, 3% gelatin gave the best contrast between green for the healthy samples, and purple color for infected samples.

Breakthrough in the direct conversion of methane into c1-oxygenates.

The partial oxidation of methane to CH3OH and HCHO (C1-oxygenates) was evaluated over a low surface area V2O5/SiO2 catalyst. The introduction of low amounts of NO (0-2.92% vol) to the reaction feed strongly enhanced both the conversion of methane and selectivity to C1-oxygenates. In the presence of NO, both the reaction temperature and the CH4/O2 ratio affected selectivity to CH3OH and HCHO. Selectivity values of C1-oxygenates as high as 40% at a methane conversion close to 40% were obtained.

Folate levels and N(5),N(10)-methylenetetrahydrofolate reductase genotype (MTHFR) in mothers of offspring with neural tube defects: a case-control study.

BACKGROUND: Neural tube defects (NTDs) have been associated with biochemical factors involved in the conversion of homocysteine to methionine as folate deficiency and the mutation 677T in the N(5),N(10)-methylenetetrahydrofolate reductase gene (MTHFR). METHODS: A case-control study was performed to detect this mutation in 38 unrelated women with NTD deceased products and 31 mothers without antecedents of NTD offspring. All products were born in Nuevo León (northeastern Mexico) during 1997. Erythrocyte and plasmatic folate levels and the genotype of the 677 polymorphism at the MTHFR locus were analyzed in both groups. RESULTS: Although no significant differences were found in mean blood folate levels, the percentage of women in the case group with erythrocyte folate levels <160 ng/mL was significantly higher than in the control group (75 vs. 51.2%, p <0.05). The proportion of women with plasma folate levels <3.5 ng/mL was higher in the case group (16.2 vs. 0%, p <0.01). Genotype analysis demonstrated a significantly higher proportion of 677T homozygous mothers with NTD products (39.6 vs. 9.1%, p <0.05). Allele frequencies for the 677T mutation were 0.55 and 0.36 for cases and controls, respectively. The odds ratio (OR) for having a NTD product was 6.1 (95%, CI 1.56-23.6) for homozygous 677T mothers vs. homozygous 677C and heterozygous mothers. Significantly low levels of erythrocyte folate were found in the 677C homozygous case group and in plasma folate in the 677C/677T heterozygous case mothers. CONCLUSIONS: Our study suggests that folate deficiency and MTHFR unfavorable genotype in mothers are important risk factors for severe NTD phenotype in our population.