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.

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.

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.

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.

Effects of fetal respiratory movements on the short-term fractal properties of heart rate variability.

We evaluated the effect of fetal respiratory movements (RM) on the heart rate (HR) fractal dynamics.Abdominal ECG recordings were collected from low-middle-risk pregnant woman at rest. Mean gestational age was 34.8 ± 3.7 weeks. Ultrasound images were simultaneously acquired determining if RM were exhibited by fetuses. 13 pairs of HR series were compared. Each pair included 5 min of data from the same fetus either during the manifestation of RM or when there was no persistent indication of them. Detrended fluctuation analysis was applied to these series for obtaining the scaling exponent α1. HR series were also assessed using the conventional parameters RMSSD and HF power.The main findings of this contribution were the lack of significant changes in the scaling exponent α1 of fetal HR fluctuations as a result of RM. By contrast, HF power and RMSSD did show significant changes associated with the manifestation of fetal RM (p < 0.001 and p < 0.05, respectively). Yet the scaling exponent was the only parameter showing a significant relationship with the particular frequency of fetal RM (r s  = 0.6, p < 0.03). Given the invariability of α1 regarding the manifestation of fetal RM, we consider that the HR short-term fractal properties are convenient for assessing the cardiovascular prenatal regulation.

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.

Fractal and nonlinear changes in the long-term baseline fluctuations of fetal heart rate.

The interpretation of heart rate patterns obtained by fetal monitoring relies on the definition of a baseline, which is considered as the running average heart rate in the absence of external stimuli during periods of fetal rest. We present a study along gestation of the baseline's fluctuations, in relation to fractal and nonlinear properties, to assess these fluctuations according with time-varying attracting levels introduced by maturing regulatory mechanisms. A low-risk pregnancy was studied weekly from the 17th to 38th week of gestation during long-term recording sessions at night (>6 h). Fetal averaged pulse rate samples and corresponding baseline series were obtained from raw abdominal ECG ambulatory data. The fractal properties of these series were evaluated by applying detrended fluctuation analysis. The baseline series were also explored to evaluate nonlinear properties and time ordering by applying the scaling magnitude and sign analyses. Our main findings are that the baseline shows fractal and even nonlinear anticorrelated fluctuations. This condition was specially the case before mid-gestation, as revealed by α values near to unit, yet becoming significantly more complex after 30 weeks of gestation as indicated by α(mag) values >0.5. The structured (i.e. not random) fluctuations and particular nonlinear changes that we found thus suggest that the baseline provides on itself information concerning the functional integration of cardiac regulatory mechanisms.

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%.

Hildebrand solubility parameter to predict drug release from hydroxypropyl methylcellulose gels.

An equation including the Hildebrand solubility parameter δ of the drugs is used for the first time to model drug release from hydroxypropyl methylcellulose (HPMC) gels: l nM = -21.578 + 2.102 δ-0.037 δ(2)+0.48 ln t + 1.028 ln C(i) (r(2) = 0.94 for a total of 286 cases). The experimentally determined release data of six drugs having different polarity (caffeine, theophylline, paracetamol, salicylic acid, naproxen and diclofenac) at several initial concentrations C(i) were included in the equation. In general, the amount of drug delivered is linear at the first 5-6h of the release profiles and the zero order constants K(o) increase as the solubility parameter of the drugs become larger. The Peppas exponential law M/M(∞) = Kt(n) is applicable to larger fractional release, until 67-87% (48-51 h) for the less polar drugs (diclofenac and naproxen, lower δ values) and more than 80% (26-28 h) for the more polar drugs (higher δ values, theophylline, salicylic acid, caffeine and paracetamol). The Peppas release rate (lnK) shows a parabolic relationship with the drug solubility parameter. The diffusional exponent n varies between 0.40 and 0.58 indicating that drug release is mainly controlled by diffusion. An extended form of the Peppas equation is also tested for each drug including all the initial concentrations: lnM = a + b ln t + c ln C(i) (r(2) = 0.88-0.94). The logarithm of the octanol-water partition coefficients can also be used in combination with the drug concentrations.

Short-term heart rate dynamics of pregnant women.

Aiming to detect the stage of gestation where dynamical changes of the RR fluctuations may occur, we assessed short-term fluctuations of low risk pregnant women. Ninety six, 10min ECG recordings were collected along gestation (7 to 39 weeks). Corresponding RR fluctuations series were analysed to obtain the RMSSD, α(1), α(1(mag)) and α(1(sign)) parameters. Four groups covering first, second and last trimesters of gestation were conformed. No significant changes in α(1), which was close to unit, and α(1(sign)) among gestational groups were identified. But, in accordance with previous findings, we did find a significant reduction of RMSSD along gestation, and significant short-term changes that indicate a higher degree of nonlinearity after about 26 weeks of gestation (α(1(mag))>0.5)). These results suggest that the short-term heart rate dynamics of low risk pregnant women do not become compromised during gestation, despite the increased haemodynamic demands and other ongoing adaptations. Yet the complexity of the mechanisms involved in the cardiac regulation of pregnant women does seem to increase from mid-pregnancy, possibly owing to new short-term control influences or to modifications regardless the strength of the regulatory interactions.

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.

Short-term heart rate dynamics of women during labor.

We studied 10 minutes segments of heartbeat interval fluctuations from 18 young women in labor with normal outcome of pregnancy. Data of each studied case were classified into two distinct groups. One group involving segments where the uterine activity was observable (three or more contractions in ten minutes), and the other group of reference having segments with fewer uterine activity or not presenting contractions at all. For comparison, we also included segments collected during the last trimester of gestation prior to labor from a third group of women. Corresponding RR interval series were analyzed to estimate RR(mean), RMSSD, α(1), α(1(MAG)) and α(1(SIGN)) parameters. No significant differences among groups were identified in RMSSD, α(1) and α(1(MAG)) Nevertheless, α(1(SIGN)) did present significant differences in comparison with the last trimester results (p<0.007), revealing a subtle change in the temporal organization of maternal RR series during labor. Results of these parameters then suggest that during labor, despite preserving a concomitant non-linear influence, the maternal short-term autonomic cardiac regulation behaves with less antagonism.

Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on the development of bovine embryos produced in vitro.

This study examined the influence of the following growth factors and cytokines on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF-II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF-beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture medium. We studied the development of bovine embryos produced in vitro and cultured until Day 9 after fertilization. TGF-beta1, bFGF, GM-CSF, and LIF used on their own significantly improved the yield of hatched blastocysts. IGF-I, bFGF, TGF-beta1, GM-CSF, and LIF significantly accelerated embryonic development, especially the change from the expanded blastocyst to hatched blastocyst stages. Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium produced higher percentages of blastocysts and hatched blastocysts than did use of SOF alone (45% and 22% vs. 24% and 12%; P<0.05) on Day 8 after in vitro fertilization and similar results to use of SOF+10% fetal calf serum (38% and 16%, at the same stages, respectively). The averages of total cells, inner cell mass cells, and trophectoderm cells of exclusively in vitro Day-8 blastocysts for pooled GF-CYK treatments were higher than those for SOF and similar to those for fetal calf serum. The presence of these growth factors and cytokines in the embryo culture medium therefore has a combined stimulatory action on embryonic development; in particular through an increase in hatching rate and in the number of cells of both the inner cell mass and trophoblast. These results are the first to demonstrate that use of a combination of recombinant growth factors and cytokine, as IGF-I, IGF-II, bFGF, TGF-beta1, LIF, and GM-CSF, produces similar results to 10% fetal calf serum for the development of in vitro-produced bovine embryos. This entirely synthetic method of embryo culture has undeniable advantages for the biosecurity of embryo transfer.

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.

Effects of dietary fibre intake on risk factors for cardiovascular disease in subjects at high risk.

BACKGROUND: Epidemiological studies and feeding trials with supplements suggest that fibre intake is associated with a reduction in cardiovascular risk. However, the effects of changes in dietary fibre on risk factor levels have not been evaluated in free-living individuals. Thus, the effects of changes in dietary fibre intake on cardiovascular risk factors were assessed over 3 months in free-living high-risk subjects. METHODS: 772 high-risk subjects (age 69+/-5 years) were assigned to a low-fat diet or two Mediterranean-style diets. All participants received behavioural and nutritional education, including recommendations for increasing the consumption of vegetables, fruits, and legumes. Changes in food and nutrient intake, body weight, blood pressure, lipid profiles, glucose control and inflammatory markers were evaluated. RESULTS: Most participants increased consumption of vegetable products, but the increase in dietary fibre exhibited wide between-subject variability (6-65 g/day). Body weight, waist circumference, and mean systolic and diastolic blood pressure decreased across quintiles of fibre intake (p<0.005; all). Reductions in fasting glucose and total cholesterol levels, and increments in HDL cholesterol were highest among participants in the upper 20% of fibre intake (p = 0.04 and 0.02 respectively). Plasma concentrations of C-reactive protein, but not those of inflammatory cytokines, decreased in parallel with increasing dietary fibre (p = 0.04). Significant reductions in LDL cholesterol were observed only among participants with the greatest increases in soluble fibre intake (p = 0.04). CONCLUSIONS: Increasing dietary fibre intake with natural foods is associated with reductions in classical and novel cardiovascular risk factors in a high-risk cohort.

Applying fractal analysis to short sets of heart rate variability data.

The aim of this study was to explore the interchangeability of fractal scaling exponents derived from short- and long-term recordings of real and synthetic data. We compared the alpha(1) exponents as obtained by detrended fluctuation analysis from RR-interval series (9 am to 6 pm) of 54 adults in normal sinus rhythm, and the alpha(1) estimated from shorted segments of these series involving only 50, 100, 200 and 300 RR intervals. Three series of synthetic data were also analysed. The principal finding of this study is the lack of individual agreement between alpha(1) derived from long and short segments of HRV data as indicated by the existence of bias and low intraclass correlation coefficient (r(i) = 0.158). The extent of variation in the estimation of alpha(1) from real data does not only appear related to segments' length, but also to different dynamics among subjects or lack of uniform scaling behaviour. However, we did find statistical agreement between the means of alpha(1) exponents from long and short segments, even for segments involving just 50 RR intervals. According to results of synthetic series, the 95% confidence interval found for the variation of alpha(1) using segments with 300 samples is [-0.1783 + 0.1828]. Caution should be taken concerning the use of short segments to obtain representative exponents of fractal RR dynamics; a circumstance not fully considered in several studies.

Thermodynamics of cosolvent action: phenacetin, salicylic acid and probenecid.

The solubility of phenacetin, salicylic acid, and probenecid in ethanol-water and ethanol-ethyl acetate mixtures at several temperatures (15-40 degrees C) was measured. The solubility profiles are related to medium polarity changes. The apparent thermodynamic magnitudes and enthalpy-entropy relationships are related to the cosolvent action. Salicylic acid and probenecid show a single peak against the solubility parameter delta(1) of both solvent mixtures, at 40% (delta(1) = 21.70 MPa(1/2)) and 30% (delta(1) = 20.91 MPa(1/2)) ethanol in ethyl acetate, respectively. Phenacetin displays two peaks at 60% ethanol in ethyl acetate (23.30 MPa(1/2)) and 90% ethanol in water (delta(1) = 28.64 MPa(1/2)). The apparent enthalpies of solution display a maximum at 30% (phenacetin and salicylic acid) and 40% (probenecid) ethanol in water, respectively. Two different mechanisms, entropy at low ethanol ratios, and enthalpy at high ethanol ratios control the solubility enhancement in the aqueous mixture. In the nonaqueous mixture (ethanol-ethyl acetate) enthalpy is the driving force throughout the whole solvent composition for salicylic acid and phenacetin. For probenecid, the dominant mechanism shifts from entropy to enthalpy as the ethanol in ethyl acetate concentration increases. The enthalpy-entropy compensation plots corroborate the different mechanisms involved in the solubility enhancement by cosolvents.

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.