Where to next with animal health in Latin America? The transition from endemic to disease-free status.

The Latin American and Caribbean region (LAC) is a leading global producer and exporter of animal products. Its livestock production systems are diverse, ranging from large-scale commercial enterprises to family farms. Countries in this region have sought to improve their animal health status through both public and private efforts. Despite significant advances in eradicating such diseases as foot and mouth disease and classical swine fever, other animal health challenges remain; constraining exports, causing negative economic impacts and threatening food security. Obtaining certification of disease-free status is only the first step towards gaining benefits from improvements in animal health. Increasing international trade means that countries must manage the sustainability of their disease-free status in conjunction with trade partners and must comply with additional food safety and animal welfare standards. This paper comments on the challenges created by this new scenario in relation to the epidemiology and economics of animal health, when seeking to improve decisionmaking for animal health management. The authors characterise the current LAC livestock landscape and animal health situation, describing transitions in disease control and the use of economics in improving animal health. They conclude with remarks on the challenges presented by decision-making, economic rationality, sources of benefits, distribution and incentives.

La région Amérique latine et Caraïbes est l'une des principales régions productrices et exportatrices de produits d'origine animale dans le monde. Les systèmes de production du secteur de l'élevage y sont très diversifiés, depuis les petites exploitations familiales jusqu'aux élevages commerciaux à grande échelle. Les pays de la région ont cherché à améliorer la situation de la santé animale sur leur territoire en y consacrant les efforts de leur secteur public et privé. Malgré les avancées considérables réalisées dans l'éradication de maladies comme la fièvre aphteuse et la peste porcine classique, la santé animale est encore confrontée à des problèmes qui freinent les exportations et ont un impact économique négatif, tout en menaçant la sécurité de l'approvisionnement alimentaire. La reconnaissance officielle du statut indemne de maladie ne représente qu'une première étape dans le processus visant à générer des bénéfices grâce à une meilleure santé animale. L'intensification des échanges internationaux impose aux pays de s'assurer de la durabilité de leur statut indemne aux côtés de leurs partenaires commerciaux et de respecter de nouvelles normes relatives à la sécurité sanitaire des aliments et au bien-être animal. Les auteurs analysent les conséquences de ce scénario sur l'épidémiologie et l'économie de la santé animale ainsi que ses enjeux dans la recherche d'une meilleure prise de décisions dans la gestion de la santé animale. Ils définissent ensuite le paysage actuel de l'élevage et la situation de la santé animale en Amérique latine et dans les Caraïbes et décrivent les évolutions à l'oeuvre en matière de lutte contre les maladies animales et d'utilisation de l'économie dans l'amélioration de la santé animale. Ils concluent sur quelques remarques concernant les difficultés qui se présentent en matière de prise de décision, de rationalité économique, de sources de profit, de distribution et d'incitation.

La región de América Latina y el Caribe es uno de los principales productores y exportadores de productos animales del mundo. Sus sistemas de producción ganadera exhiben gran heterogeneidad, pues van desde las grandes empresas de dimensión industrial hasta las pequeñas explotaciones familiares. Apoyándose en la iniciativa tanto pública como privada, los países de la región vienen tratando de mejorar su situación zoosanitaria. Pese a los importantes progresos registrados en la erradicación de enfermedades como la fiebre aftosa o la peste porcina clásica, subsisten otros problemas de sanidad animal que restringen las exportaciones, lastran la economía y amenazan la seguridad alimentaria. La certificación de «ausencia de enfermedad¼ es solo el primer paso para beneficiarse de las mejoras conseguidas en el terreno de la sanidad animal. Habida cuenta de la intensificación del comercio internacional, los países deben gestionar la continuidad a largo plazo de su estatuto de «libres de enfermedad¼ conjuntamente con sus socios comerciales y, para ello, cumplir normas adicionales en material de inocuidad de los alimentos y bienestar animal. Los autores exponen las dificultades que se plantean en esta nueva coyuntura de la epidemiología y la economía de la sanidad animal a la hora de mejorar los procesos decisorios en materia de gestión zoosanitaria. Tras caracterizar el actual paisaje de la ganadería y la situación zoosanitaria en América Latina y el Caribe, describen la transición que se está operando en cuanto al control de enfermedades y al uso de la economía para mejorar la sanidad animal y concluyen con una serie de observaciones sobre los problemas que surgen en relación con la adopción de decisiones, la racionalidad económica, las fuentes de beneficios y las cuestiones ligadas a la distribución y los incentivos.

Evaluation of the non-catalytic binding function of Ts26GST a glutathione transferase isoform of Taenia solium.

Taenia solium glutathione transferase isoform of 26.5 kDa (Ts26GST) was observed to bind non-catalytically to porphyrins, trans-trans-dienals, bile acids and fatty acids, as assessed by inhibition kinetics, fluorescence spectroscopy and competitive fluorescence assays with 8-anilino-1-naphthalene sulfonate (ANS). The quenching of Ts26GST intrinsic fluorescence allowed for the determination of the dissociation constants (KD) for all ligands. Obtained data indicate that Ts26GST binds to all ligands but with different affinity. Porphyrins and lipid peroxide products inhibited Ts26GST catalytic activity up to 100% in contrast with only 20-30% inhibition observed for bile acids and two saturated fatty acids. Non-competitive type inhibition was observed for all enzyme inhibitor ligands except for trans-trans-2,4-decadienal, which exhibited uncompetitive type inhibition. The dissociation constant value KD = 0.7 µM for the hematin ligand, determined by competitive fluorescence assays with ANS, was in good agreement with its inhibition kinetic value Ki = 0.3 µM and its intrinsic fluorescence quenching KD = 0.7 µM. The remaining ligands did not displace ANS from the enzyme suggesting the existence of different binding sites. In addition to the catalytic activity of Ts26GST the results obtained suggest that the enzyme exhibits a ligandin function with broad specificity towards nonsubstrate ligands.

Using Ant Programming Guided by Grammar for Building Rule-Based Classifiers.

The extraction of comprehensible knowledge is one of the major challenges in many domains. In this paper, an ant programming (AP) framework, which is capable of mining classification rules easily comprehensible by humans, and, therefore, capable of supporting expert-domain decisions, is presented. The algorithm proposed, called grammar based ant programming (GBAP), is the first AP algorithm developed for the extraction of classification rules, and it is guided by a context-free grammar that ensures the creation of new valid individuals. To compute the transition probability of each available movement, this new model introduces the use of two complementary heuristic functions, instead of just one, as typical ant-based algorithms do. The selection of a consequent for each rule mined and the selection of the rules that make up the classifier are based on the use of a niching approach. The performance of GBAP is compared against other classification techniques on 18 varied data sets. Experimental results show that our approach produces comprehensible rules and competitive or better accuracy values than those achieved by the other classification algorithms compared with it.

Pediatric group B coxsackievirus infections.

The CVB have long been recognized as significant pathogens of infants and children. Although the major route for transmission of the CVB is fecal-oral, vertical transmission from mother to infant is also possible. This review will focus on the more common or clinically relevant CVB-related syndromes, their diagnosis, treatment, and prevention.

Dynamics of Eimeria oocyst excretion in dairy calves in the Province of Buenos Aires (Argentina), during their first 2 months of age.

Clinical coccidiosis is associated with high fecal contamination and stress situations, mainly in animals under 1 year of age. Artificially fed dairy calves are one of the categories most prone to suffer from this parasitic disease. The study was carried out in a commercial dairy farm. Feces samples of heifer calves between 2 and 8 weeks old were taken monthly for oocyst counts and Eimeria spp. identification. Of the 862 feces samples analyzed, 48% presented oocysts. When grouping the results of monthly samplings of each age group, it was observed that this percentage increased in the group of calves between 20 and 40 days of life, reaching the peak average of 85% of infection prevalence in the group with between 26 and 30 days of age. The discharge of oocysts observed between 21 and 35 days of age was superior to the rest (p<0.05). This trend appeared every month throughout the whole year. However, during March, April, June, September and November, the curves in the group categories were higher than in the remaining months (p<0.05). Twelve Eimeria species were identified, being E. ellipsoidalis, E. bovis, E. zuernii and E. auburnensis those in highest numbers. E. ellipsoidalis had an important predominance in the opg composition, >75% up to 25 days of life (p<0.05). E. bovis reached peak values in the 26 and 30 days group (p<0.05), remaining without significant variations in the last stage of the artificial milk feeding period (approximately 60 days of life), when the oocyst counts were significantly low. Oocysts of E. auburnensis appeared in great proportion (46%) in the cultures later than the previous species (p<0.05), in calves of the age groups of between 46 and 50 days of age. Oocysts of E. zuernii showed no trend associated with age. The highest prevalence of infection and of oocyst values appeared during the periods with better environmental conditions for sporulation, survival and dispersion of oocysts (spring and autumn), coincident with the highest birth rates and an elevated number of calves in the paddock. Calves developed a process of natural "vaccination" against coccidiosis. This was demonstrated by the decrease in the quantity of animals shedding oocysts and in the number of oocysts eliminated at the end of the artificial milk feeding period.

Ganciclovir population pharmacokinetics in neonates following intravenous administration of ganciclovir and oral administration of a liquid valganciclovir formulation.

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.

[Metastasis in maxilar sinus as only manifestation of disseminate renal adenocarcinoma]. / Metástasis en seno maxilar como única manifestación de adenocarcinoma renal diseminado.

Paranasal sinuses and nose metastasis are very uncommon. About 50 have been reported. Renal cell carcinoma is the primary neoplasm which most frequently metastasizes in the nasosinusal region, followed by breast and lug. Symptoms are unspecific, but the epistaxis constitutes the most common sign due to the significant vascularizations of the tumor. Prognosis is poor. The survival rate fluctuates between 15-30% at 5 years. Surgery is the elective treatment.

Temporal and spatial expression of genes involved in DNA methylation during reproductive development of sexual and apomictic Eragrostis curvula.

Recent reports in model plant species have highlighted a role for DNA methylation pathways in the regulation of the somatic-to-reproductive transition in the ovule, suggesting that apomixis (asexual reproduction through seeds) likely relies on RdDM downregulation. Our aim was therefore to explore this hypothesis by characterizing genes involved in DNA methylation in the apomictic grass Eragrostis curvula. We explored floral transcriptomes to identify homologs of three candidate genes, for which mutations in Arabidopsis and maize mimic apomixis (AtAGO9/ZmAGO104, AtCMT3/ZmDMT102/ZmDMT105, and AtDDM1/ZmCHR106), and compared both their spatial and temporal expression patterns during reproduction in sexual and apomictic genotypes. Quantitative expression analyses revealed contrasting expression patterns for the three genes in apomictic vs sexual plants. In situ hybridization corroborated these results for two candidates, EcAGO104 and EcDMT102, and revealed an unexpected ectopic pattern for the AGO gene during germ line differentiation in apomicts. Although our data partially support previous results obtained in sexual plant models, they suggest that rather than an RdDM breakdown in the ovule, altered localization of AtAGO9/ZmAGO104 expression is required for achieving diplospory in E. curvula. The differences in the RdDM machinery acquired during plant evolution might have promoted the emergence of the numerous apomictic paths observed in plants.

[Maxillary sinus metastasis of renal cell carcinoma]. / Adenocarcinoma renal metastásico en seno maxilar.

Paranasal sinuses and nose metastasis are very uncommon tumors, about 50 have been reported. Renal cell carcinoma is the primary neoplasm which most frequently metastasizes in the nasosinusal region, followed by breast and lung. Symptoms are unspecific, but the epistaxis constitutes the most common sign due to the significant vascularizations of the tumor. Prognosis is poor. The survival rate fluctuates between 15-30% at 5 years. Surgery is the elective treatment.

Genetic divergence among the group B coxsackieviruses.

As documented in the preceding discussion, the noncoding regions, and in particular the 5' NTR, of the CVB are tolerant of a substantial degree of nucleotide diversity while still being capable of fulfilling the life cycle requirements for these viruses. While diversity among the CVB is observed in the sequences encoding for the capsid proteins, it tends to involve predominantly those regions coding for amino acids located at the surface of the virus and not those responsible for the structural integrity of the mature virion, i.e., beta-barrels and alpha-helices. It is these capsid surface differences that define the six serotypes of the CVB and subdivide them antigenically into strains. Additionally, these proteins most likely play the major role in determining host and cellular tropism. The most conserved of the CVB proteins and, therefore those with the least diversity in their coding sequences, appear to be the nonstructural proteins. Perhaps, as speculated earlier, it is a conformational requirement imposed by the necessity to interact with host or viral substrates that maintains the high degree of amino acid identity of this group of viral proteins.

Pleconaril: a novel antipicornaviral drug.

Pleconaril (VP-63843) 3-[3,5-dimethyl-4[[3-(3-methyl-5-isoxazolyl)propyl] oly]phenyl]-5-(trifluoromethyl)-1,2,4-oxadiazole is a novel, broad spectrum antipicornaviral agent. Pleconaril binds to a hydrophobic pocket in the viral capsid inducing conformational changes, which lead to altered receptor binding and viral uncoating. Pleconaril is orally bioavailable and achieves serum concentrations in excess of those required to inhibit 90% of clinical rhino- and enteroviral isolates in vitro. It possesses the additional advantage of achieving several fold higher concentrations within the central nervous system and nasal secretions than in serum, a characteristic that is highly desirable for an antiviral targeted towards viruses known to cause central nervous system and upper respiratory tract infections. Approximately 80% of an orally administered dose is excreted in the faeces within 48 h. Urine excretion accounts for the remainder of the drug. Pleconaril has demonstrated an excellent safety profile in dose escalation and clinical studies. Clinical studies have reported a reduction in the duration and intensity of symptoms in children and adults with enteroviral meningitis and in adults with rhinoviral respiratory tract infections treated with pleconaril. Lastly, pleconaril has demonstrated efficacy in the treatment of severe life-threatening enteroviral infections of the newborn and in immunosuppressed individuals. Pleconaril appears to be a promising drug for the treatment of enteroviral and rhinoviral infections.

Transcranial magnetic stimulation coregistered with MRI: a comparison of a guided versus blind stimulation technique and its effect on evoked compound muscle action potentials.

INTRODUCTION AND METHODS: Compound muscle action potentials (CMAPs) elicited by transcranial magnetic stimulation (TMS) are characterized by enormous variability, even when attempts are made to stimulate the same scalp location. This report describes the results of a comparison of the spatial errors in coil placement and resulting CMAP characteristics using a guided and blind TMS stimulation technique. The former uses a coregistration system, which displays the intersection of the peak TMS induced electric field with the cortical surface. The latter consists of the conventional placement of the TMS coil on the optimal scalp position for activation of the first dorsal interossei (FDI) muscle. RESULTS: Guided stimulation resulted in significantly improved spatial precision for exciting the corticospinal projection to the FDI compared to blind stimulation. This improved precision of coil placement was associated with a significantly increased probability of eliciting FDI responses. Although these responses tended to have larger amplitudes and areas, the coefficient of variation between guided and blind stimulation induced CMAPs did not significantly differ. CONCLUSION: The results of this study demonstrate that guided stimulation improves the ability to precisely revisit previously stimulated cortical loci as well as increasing the probability of eliciting TMS induced CMAPs. Response variability, however, is due to factors other than coil placement.

Increased red cell sodium-lithium countertransport and lymphocyte cytosolic calcium are separate phenotypes in patients with essential hypertension.

Increased red blood cell sodium-lithium countertransport (SLC) activity and elevated intracellular calcium have been observed in hypertensive patients. The association of these ion transport abnormalities with each other and with another phenotype, insulin resistance, has been suggested. We investigated whether elevated SLC activity and increased lymphocyte cytosolic calcium (Ca(cyt)) occur in the same individuals and whether either is associated with hyperinsulinaemia. We measured SLC activity, lymphocyte Ca(cyt)and fasting insulin levels in hypertensive patients and normal subjects. Consistent with prior studies, SLC activity was significantly and positively correlated with fasting insulin levels (r = 0.45, P < 0.01). However, SLC activity and lymphocyte Ca(cyt) were significantly but inversely correlated (r = -0.42, P < 0.01) and lymphocyte Ca(cyt) was also inversely correlated with fasting insulin (r = -0.55, P < 0.001). When the study participants were instead separated into two groups based on fasting insulin levels, those above the median (15 microU/ml) had significantly higher SLC activity and significantly lower Ca(cyt). When separated by lymphocyte Ca(cyt) levels (above or below 120 nM) those patients with low lymphocyte Ca(cyt) had significantly higher SLC activity and significantly higher insulin levels. Multiple linear regression showed that fasting insulin was significantly predictive of SLC activity (P = 0.05) and Ca(cyt) (P < 0.01). Thus, elevated SLC activity and increased lymphocyte Ca(cyt) are separate and distinct ion transport phenotypes in hypertensive patients, linked through a relationship to hyperinsulinaemia that is direct with SLC activity and inverse with lymphocyte Ca(cyt).

The protective effect of brachial plexus palsy in purpura fulminans.

Acute infectious purpura fulminans is reported in a 16-month-old male with a history of posttraumatic asplenia and complete left brachial plexus palsy. This patient developed peripheral necrosis of both lower extremities and the right upper extremity, whereas the left upper extremity was completely spared from ischemia and tissue damage. Amputation of four digits on the right hand and debridement of both lower extremities were required. This patient demonstrated the protective effect of a traumatic sympathectomy, which suggests the requirement of an intact sympathetic reflex in the development of purpura fulminans.

Lipid and fatty acid composition of canine lipoproteins.

Lipid classes and their fatty acids were studied in the major lipoprotein fractions from canine, in comparison with human, plasma. In dogs, high-density-lipoprotein (HDL), the main carrier of plasma phospholipid (PL), cholesterol ester (CE) and free cholesterol, was the most abundant lipoprotein, followed by low and very-low density lipoproteins (LDL and VLDL). Notably, LDL and VLDL contributed similarly to the total dog plasma triacylglycerol (TG). The PL composition was similar in all three lipoproteins, dominated by phosphatidylcholine (PC). Even though the content and composition of lipids within and among lipoproteins differed markedly between dog and man, the total amount of circulating lipid was similar. All canine lipoproteins were relatively richer than those from humans in long-chain (C20-C22) n-6 and n-3 polyunsaturated fatty acids (PUFA) but had comparable proportions of total saturated and monoenoic fatty acids, with 18:2n-6 being the main PUFA in both mammals. The fatty acid profile of canine and human lipoproteins differed because they had distinct proportions of their major lipids. There were more n-3 and n-6 long-chain PUFA in canine than in human plasma, because dogs had more HDL, their HDL had more PC and CE, and both these lipids were richer in such PUFA.

Hepatic zonation of the formation and hydrolysis of cholesteryl esters in periportal and perivenous parenchymal cells.

The periportal (PP) and perivenous (PV) zones of the liver acinus differ in enzyme complements and capacities for cholesterol and bile acid synthesis and other metabolic processes. The aim of this investigation was to determine the acinar distribution of the catalytic activity of the enzymes governing the formation and hydrolysis of cholesteryl esters using PP and PV hepatocytes from normal or cholestyramine-fed rats. The hepatocyte subpopulations were isolated by centrifugal elutriation, characterized according to the distribution pattern of a number of cell parameters and marker enzymes, and assayed for acyl-CoA:cholesterol acyltransferase (ACAT) and lysosomal, cytosolic and microsomal cholesteryl ester hydrolase (CEH). In normally fed rats, no zonation was found in the activity of lysosomal CEH and ACAT, and the activity of both cytosolic and microsomal CEH zonated toward the PV zone of the acinus. Concentrations of free and esterified cholesterol in homogenates, cytosol, and microsomes of PP and PV cells were, however, similar. Cholestyramine raised significantly the PV/PP ratio of ACAT because of an exclusive PP reduction of activity and abolished the heterogeneity in microsomal CEH because of a greater inhibitory PV response, whereas the PV dominance of cytosolic CEH and the homogeneous distribution of lysosomal CEH were unaffected. These results demonstrated homogeneity within the liver acinus for the enzymatic degradation of endocyted lipoprotein-derived cholesteryl esters, a structural zonation of the cytosolic CEH and a dynamic zonation of ACAT and the microsomal CEH, with a PV dominance of the enzymatic capacity for the degradation of stored cholesteryl esters in normal livers.

Application of 2-hydroxypropyl-beta-cyclodextrin in the assay of acyl-CoA:cholesterol acyltransferase and neutral and acid cholesterol ester hydrolases.

The utility of 2-hydroxypropyl-beta-cyclodextrin for increasing the sensitivity of assays for the microsomal acylCoA:cholesterol acyltransferase, and the acid lysosomal and the neutral microsomal and cytosolic cholesterol ester hydrolase activity was studied in rat hepatocytes. Enzyme assays, at optimal concentrations of cyclodextrin, were validated by assessing: (i) linearity of product formation with incubation time and protein amount, and saturation with substrate, and (ii) the effect of treatments of cells or of subcellular fractions on enzyme activities. Delivery of cholesterol dissolved in 2-hydroxypropyl-beta-cyclodextrin to the acyl-CoA:cholesterol acyltransferase assay mixture raised the enzyme activity more than 8-fold and was twice that measured when cholesterol was added in Triton WR-1339. 2-Hydroxypropyl-beta-cyclodextrin itself was partially effective, apparently by making endogenous cholesterol more accesible to the enzyme. Inclusion of 2-hydroxypropyl-beta-cyclodextrin in cholesterol ester hydrolase assays using standard micellar substrates doubled the activity estimated in lysosome and microsome preparations and enhanced the cytosolic cholesterol esterase activity by about 50%. Differences in the catalytic activity of acyl-CoA:cholesterol acyltransferase and cholesterol ester hydrolases caused by treatment of hepatocytes with compound 58-035 or 25-hydroxycholesterol, or of subcellular fractions with NaF, were maintained when enzymes were assayed with cyclodextrin. The results indicate that 2-hydroxypropyl-beta-cyclodextrin is a suitable vehicle for delivering cholesterol to acyl-CoA:cholesterol acyltransferase and enhances the sensitivity of standard assays of the enzymes governing the intrahepatic hydrolysis of cholesteryl esters.

Reverse-transcription polymerase chain reaction detection of the enteroviruses.

OBJECTIVE: This review focuses on commercial and in-house-developed reverse-transcription polymerase chain reaction (RT-PCR) assays used for the detection of enteroviral infections. In addition to providing details on the performance of RT-PCR, its specificity, and sensitivity, the clinical utility of this diagnostic method with specific reference to its impact on hospitalization and cost savings is addressed. DATA SOURCES: MEDLINE was searched for reports relating to RT-PCR detection of the enteroviruses in adults and children. The search was restricted to studies reported in English language journals. STUDY SELECTION: Reports documenting detailed information regarding the RT-PCR conditions, primers, sensitivity, specificity and, if relevant, clinical impact were selected for analysis. DATA EXTRACTION: Details regarding method of extraction of the enteroviral genome, the primers used, RT-PCR conditions, and sensitivity and specificity of the assay were extracted from the literature. For reports detailing the use of RT-PCR in the clinical management of enteroviral infections in children, the reduction in duration of hospitalization and health care cost savings were recorded. DATA SYNTHESIS: Reverse-transcription PCR can increase the yield of detection of enteroviruses from cerebrospinal fluid by a mean of approximately 20% over tissue culture. Reverse-transcription PCR of cerebrospinal fluid has been shown to exhibit sensitivity and specificity values of 86% to 100% and 92% to 100%, respectively. Reductions of 1 to 3 days of hospitalization per patient are predicted if RT-PCR is used to diagnose enteroviral meningitis in children. CONCLUSIONS: Reverse-transcription PCR detection of enteroviral infections is an extremely rapid, sensitive, and specific diagnostic modality. Both commercial assays and assays developed in-house appear to be equivalent with regard to sensitivity and specificity. Reverse-transcription PCR diagnosis of enteroviral infections in children could reduce the length of hospitalization and result in significant health care cost savings.

The pharmacokinetics of a single dose of calcitriol administered subcutaneously in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: To evaluate the kinetics of calcitriol (1,25(OH)2D3) administered subcutaneously. STUDY DESIGN: Calcitriol kinetics and efficacy after subcutaneous administration were studied in 13 CAPD patients with varying degrees of increased plasma levels of parathyroid hormone (i-PTH). A single dose of 2 micrograms of calcitriol was administered subcutaneously, and its serum levels at baseline and after 1, 2, 6, 12, and 24 hours were determined. Plasma ionized calcium and i-PTH were also determined at these periods. RESULTS: Serum calcitriol levels reached peak levels of 60 and 70 pg/mL at 1 and 2 hours after administration, respectively. These levels decreased thereafter, but remained above baseline values during 24 hours. The mean value of the area under the curve (AUC) was 809 +/- 226 pg/mL/hour. Plasma i-PTH levels showed a slight decrease after 1 and 2 hours, returning to baseline levels after this period. Plasma ionized calcium did not show significant changes during the study. A slight pain at the site of injection was mentioned by some patients. CONCLUSIONS: The subcutaneous route for calcitriol administration achieves theoretically adequate plasma levels in continuous ambulatory peritoneal dialysis (CAPD) patients. This is important when parenteral administration of calcitriol is considered in the treatment of secondary hyperparathyroidism.

Cell populations present in the nocturnal peritoneal effluent of patients on continuous ambulatory peritoneal dialysis and their relationship with peritoneal function and incidence of peritonitis.

OBJECTIVE: To study the relationship between peritoneal effluent cells and infection rate and to relate this population with functional characteristics. DESIGN: Prospective, longitudinal, and comparative study. SETTING: Outpatient continuous ambulatory peritoneal dialysis (CAPD) unit of a university medical center. PARTICIPANTS: Seventy-one uninfected patients, treated for 0-156 months on CAPD, in stable condition were studied (33 female, 38 male). INTERVENTIONS: Nocturnal peritoneal effluent (NPE) was drained with EDTA (2.5 mmol/L) at 37 degrees C and centrifuged at 2500 rpm for 9 minutes. MEASUREMENTS: Accumulated peritoneal inflammation days/year and ultrafiltration/diffusion (mass transfer coefficients (MTCs) for small molecules) capacities were recorded. Cellular count (cells/night) was performed using a Neubauer chamber. Macrophage function was assessed by cytochemical (lysosomal enzyme content: ANAE, beta-glucuronidase, acid phosphatase) and immunohistochemical procedures (expression of membrane antigens, CD4, 11b, 11c, 14, 16, 25, 35, and 71). RESULTS: The macrophage is the most frequently appearing cell in the NPE. Cell count decreases over time on CAPD (from 20 x 10(6) to 5 x 10(6) after the first year). Intrapatient variability was low, but interpatient differences were marked. Mesothelial cell count remained stable over time (0.25-0.5 x 10(6)). Four of our patients showed a "transforming" change in these cells. Previous incidence of peritonitis and values of functional measurements did not correlate with cell count or expressions of macrophage function (lysosome enzyme content and percentage of cells expressing different membrane antigens). CONCLUSION: There is difficulty interpreting the results on peritoneal effluent cells and their relationship with the incidence of peritonitis and functional characteristics of the peritoneum. No definite conclusions can be drawn other than the great interpatient and intrapatient variability. The presence of abnormal peritoneal cells with undetermined origin and function suggests the need for periodic studies of peritoneal effluent cells on long-term CAPD patients.