Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings.

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

External quality assurance programs as a tool for verifying standardization of measurement procedures: Pilot collaboration in Europe.

INTRODUCTION: Current external quality assurance schemes have been classified into six categories, according to their ability to verify the degree of standardization of the participating measurement procedures. SKML (Netherlands) is a Category 1 EQA scheme (commutable EQA materials with values assigned by reference methods), whereas SEQC (Spain) is a Category 5 scheme (replicate analyses of non-commutable materials with no values assigned by reference methods). AIM: The results obtained by a group of Spanish laboratories participating in a pilot study organized by SKML are examined, with the aim of pointing out the improvements over our current scheme that a Category 1 program could provide. METHOD: Imprecision and bias are calculated for each analyte and laboratory, and compared with quality specifications derived from biological variation. RESULTS: Of the 26 analytes studied, 9 had results comparable with those from reference methods, and 10 analytes did not have comparable results. The remaining 7 analytes measured did not have available reference method values, and in these cases, comparison with the peer group showed comparable results. The reasons for disagreement in the second group can be summarized as: use of non-standard methods (IFCC without exogenous pyridoxal phosphate for AST and ALT, Jaffé kinetic at low-normal creatinine concentrations and with eGFR); non-commutability of the reference material used to assign values to the routine calibrator (calcium, magnesium and sodium); use of reference materials without established commutability instead of reference methods for AST and GGT, and lack of a systematic effort by manufacturers to harmonize results. CONCLUSIONS: Results obtained in this work demonstrate the important role of external quality assurance programs using commutable materials with values assigned by reference methods to correctly monitor the standardization of laboratory tests with consequent minimization of risk to patients.

Proposal for SICSeG guidelines for rehabilitation after anatomical shoulder prosthesis in concentric shoulder osteoarthritis.

PURPOSE: The purpose of this paper is to provide up-to-date guidelines on rehabilitation after anatomical shoulder prosthesis for concentric shoulder osteoarthritis, as previous guidelines date back to late 1970s and are no longer adequate due to the evolution of prosthesis models and surgical techniques. METHODS: The physiatric committee of the Italian Society of Shoulder and Elbow Surgery (SICSeG-Società Italiana di Chirurgia della Spalla e del Gomito) performed a search for all the existing literature related to rehabilitation after shoulder replacement. A total of 29 papers concerning shoulder rehabilitation were reviewed. In addition, the main Italian orthopedic surgeons and physiatrists dealing with shoulder surgery and rehabilitation were interviewed to obtain indications when literature was not conclusive. RESULTS: From literature evaluation and expert consultation, we produced guidelines concerning: patient evaluation by means of adequate rating scales, preoperative treatment, early intermediate and advanced postoperative phases, rehabilitation of scapulo-thoracic joint, return to work and sports, length of rehabilitation and follow-up. CONCLUSIONS: This proposal for guidelines was presented during the 11th SICSeG Congress on May 2012 and to the main scientific societies concerned in shoulder surgery and rehabilitation. A consensus conference is needed in order to formalize and make them usable from all the professional figures involved in this field.

Under-recognized renal insufficiency in hospitalized patients: implications for care.

BACKGROUND: The consequences of undetected low glomerular filtration rate (GFR) are important in hospitalized patients who receive potentially nephrotoxic drugs or undergo major surgery. This study estimated the prevalence of estimated GFR (eGFR) <60mL/min/1.73m(2) in hospitalized patients. METHODS: This cross-sectional descriptive study included 14,658 adults hospitalized at 10 centers in Spain. Serum samples were analyzed for hemoglobin, creatinine, albumin and urea nitrogen. eGFR was estimated using Modification of Diet in Renal Disease (MDRD) 4 or MDRD IDMS, and MDRD 6 when serum albumin and BUN were included (n=8611). Individuals were classified as having GFR>or=60mL/min/1.73m(2), stages 3, 4 and 5 (GFR 30-59, 15-29 and <15mL/min/1.73m(2), respectively). Additionally, stages 3a and 3b (GFR 45-59 and 30-44mL/min/1.73m(2), respectively) were assessed. RESULTS: MDRD 4 eGFR showed that 28.3% of patients had renal insufficiency stages 3-5 and 14.2% had stages 3b, 4 or 5, which represents important-severe renal deterioration. Forty-three percent of patients with stages 3-5 had hemoglobin or=60mL/min/1.73m(2). A good correlation was observed between eGFR MDRD 4 and MDRD 6. CONCLUSIONS: A high percentage of hospitalized patients in Spain have deteriorated renal function stages 3-5. Using eGFR equations to assess eGFR could identify more hospitalized patients with renal insufficiency, potentially leading to improved care.

Cinacalcet en pacientes en diálisis peritoneal con hiperparatiroidismo moderado-severoresistentes a tratamiento convencional. Estudio prospectivo a un año / No disponible

Objetivos: Estudiar la eficacia de Cinacalcet(R) en el cumplimiento de las recomendaciones K/DOQI en pacientes en diálisis peritoneal (DP) y estimar el tiempo necesario para alcanzarlos. Métodos: Estudio observacional prospectivo de cohorte, con pacientes con hiperparatiroidismo-HPTH moderado severo(PTH > 500 pg/ml) con más de 4 meses en DP resistentes a tratamiento convencional con dieta, quelantes y vitamina D. Los objetivos óptimos son los recomendados por las Guías NKF-K/DOQI para ERC-5D y para el análisis de objetivos subóptimos se utilizan las referencias de PTH< 350 pg/ml.; fósforo < 6 mg/dl o calcio < 10,4 mg/dl (siempre ue simultáneamente CaxP < 55 mg2/dl2).Resultados: Al inicio del tratamiento con Cinacalcet(R) los 18 pacientes llevaban 15,56 meses (DE 0,78) en DP, todos tenían una PTH > 500 pg/ml, y ninguno cumplía los objetivos K/DOQI ni los subóptimos propuestos. El seguimiento medio en tratamiento con Cinacalcet(R) fue de 12 meses. El porcentaje de pacientes con PTH < 350 pg/ml fue de 66,7%a los 3 meses 60% a los 6 y 100% al año. A los tres meses el 33,3% cumplen todos los objetivos subóptimos, a los 6 meses el 33,3% y al año el 66,7%. El tiempo medio necesario para alcanzar un valor de PTH en rango fue de 2,33meses IC al 95% [1,35-3,32] y para alcanzar todos los objetivos óptimos de 16,94 meses [11,38-22,5]. La tolerancia a la medicación ha sido buena, no se suspendió Cinacalcet(R) en ningún caso y sólo en uno se redujo la dosis por efectos secundarios. Conclusión: La utilización de Cinacalcet® en pacientes en DP con HPTH resistente a tratamiento convencional ha resultado eficaz y segura y ha permitido mejorar el cumplimiento de objetivos de las guías (AU)

Background: Cinacalcet(R) has improved the management of hyperparathiroidism(HPTH) in hemodialysis. To our knowledge there are no specific studies on peritoneal dialysis (PD).Aim: The aim of the present study was to evaluate the efficacy of Cinacalcet(R) on the achievement of optimal and suboptimal targets on treatment of hyperparathiroidism (HPTH) in PD patients. As secondary objectives we have studied the safety of treatment and estimate the mean time to reach these targets, and evaluate economic cost. Methods: Eighteen patients undergoing more than 4 months on PD with a severe HPTH (PTH > 500 pg/ml) resistant to conventional treatment with diet, chelants and vitamin D were included in this prospective open-label study. We have used the targets of K/DOQITM-clinical guidelines as optimal target. We have selected as suboptimal targets: PTH < 350 pg/ml, phosphorus< 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet(R) was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. Results: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695.3 (SD 96) and they were on PD with an appropriate efficacy during a mean of15.56 months (SD 0.78). Mean follow-up time under Cinacalcet(R) treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66.7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH < 350 pg/ml, phosphorus < 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet(R) was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. Results: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695.3 (SD 96) and they were on PD with an appropriate efficacy during a mean of 15.56 months (SD 0.78). Mean follow-up time under Cinacalcet(R) treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66.7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH < 350 pg/ml and calcium < 10.4 mg/dl and phosphorus < 6 mg/dl and CaxP < 55 mg2/dl2) was 33.3% on month 6 and 66.7% after 1 year. The mean time to reach PTH target was 2.33 months with a 95% confident interval [1,35-3,32] and to reach the aggregate of all target was 16.94 months [11,38-22,5]. Cinacalcet ® has been well tolerated, we reduced the dose in a single patient due to secondary effects, but treatment was not discontinued in any case. Conclussion: In summary the addition of Cinacalcet(R) to conventional treatment in PD patients with resistant HPTH has improved the achievement of targets, and has been reasonably safe in our patients (AU)

[Cinacalcet in patients on peritoneal dialysis with moderate to severe hyperparathyroidism resistant to conventional treatment, a one-year, prospective study]. / Cinacalcet en pacientes en diálisis peritoneal con hiperparatiroidismo moderado-severo resistentes a tratamiento convencional. Estudio prospectivo a un año.

BACKGROUND: Cinacalcet has improved the management of hyperparathiroidism (HPTH) in hemodialysis. To our knowledge there are no specific studies on peritoneal dialysis (PD). AIM: The aim of the present study was to evaluate the efficacy of Cinacalcet on the achievement of optimal and suboptimal targets on treatment of hyperparathiroidism (HPTH) in PD patients. As secondary objectives we have studied the safety of treatment and estimate the mean time to reach these targets, and evaluate economic cost. METHODS: Eighteen patients undergoing more than 4 months on PD with a severe HPTH (PTH > 500 pg/ml) resistant to conventional treatment with diet, chelants and vitamin D were included in this prospective open-label study. We have used the targets of K/DOQITM-clinical guidelines as optimal target. We have selected as suboptimal targets: PTH < 350 pg/ml, phosphorus < 6 mg/dl and calcium < 10.4 mg/dl (only when simultaneous CaxP was under 55 mg2/dl2). Oral Cinacalcet was given with main meal in a single daily start dose of 30 mg and titrated thereafter monthly. We considered the first value on target as an event and used a Kaplan-Meyer survival analysis to estimate mean time to reach target. RESULTS: On inclusion all patients have at least two previous PTH values over 500 pg/ml, PTH mean 695,3 (SD 96) and they were on PD with an appropriate efficacy during a mean of 15.56 months (SD 0.78). Mean follow-up time under Cinacalcet treatment was 12 months. The percentage of patients with a PTH under 350 pg/ml was 66,7% on month 3, 60% on month 6 and 100% after 1 year. The percentage of patients that reach an aggregate of all suboptimal targets (PTH< 350 pg/ml and calcium < 10.4 mg/dl and phosphorus< 6 mg/dl and CaxP < 55 mg2/dl2) was 33.3% on month 6 and 66.7% after 1 year. The mean time to reach PTH target was 2.33 months with a 95% confident interval [1.35-3.32] and to reach the aggregate of all target was 16.94 months [11.38-22.5]. Cinacalcet has been well tolerated, we reduced the dose in a single patient due to secondary effects, but treatment was not discontinued in any case. CONCLUSION: In summary the addition of Cinacalcet to conventional treatment in PD patients with resistant HPTH has improved the achievement of targets, and has been reasonably safe in our patients.

Non-union in an unnoticed neck fracture in resurfacing total hip arthroplasty.

The renewed popularity of resurfacing hip arthroplasty (RHA) in the last five years has generated a remarkable quantity of scientific contributions based on mid- and short-term follow-up. In spite of some large series with extremely low complication rates, more than one paper has reported a consistent early revision rate as a consequence of biological or biomechanical failure. Two major complications are commonly described with resurfacing implants: avascular necrosis and neck fracture. A close relationship between these two events has been suggested, but not firmly demonstrated, while surgical exposure and implant positioning seem to be better understood as potential causes of failure. However, it may happen that neither avascular necrosis nor neck fracture can be clearly recognised in a failed resurfacing implant: it is what we have directly experienced, with a missed fracture at the head-neck junction, evolved in non-union, beneath the dome of the femoral component. The present report, besides a brief clinical history, tries to give a possible interpretation of such an unusual complication.

Biochemical and regulatory properties of a respiratory island encoded by a conjugative plasmid in the extreme thermophile Thermus thermophilus.

In the present paper, we summarize the current knowledge on the first step of the denitrification pathway in the ancestral extreme thermophilic bacterium Thermus thermophilus. In this organism, nitrate respiration is performed by a mobilizable respiratory island that encodes a new type of respiratory NADH dehydrogenase as electron donor, a tetrameric membrane nitrate reductase as final electron acceptor, two nitrate/nitrite transporters and the transcription factors required for their expression in response to nitrate and anoxia.

The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation.

BACKGROUND: A proposal to calculate and use the reference change value (RCV) as an objective guide for interpreting the numerical results obtained in clinical laboratory serial testing is introduced in this study. METHODS: A database showing the results of a compilation of 191 publications on biological variation and including information on a number of analytes provided the standardized criterion based on biology for calculating the RCVs. RESULTS: For each of the 261 analytes included in the study, the RCV was determined using Harris's formula, replacing analytical imprecision with the desirable specification of analytical quality based on half the within-subject biological variation at 95% probability levels. The result is a guide for a common criterion to identify clinically significant changes in serial results. CONCLUSIONS: The RCV concept is an approach that can be offered by laboratories to assess changes in serial results. The RCV data in this study are presented as a point of departure for a widely applicable objective guide to interpret changes in serial results.

Biological variation of interleukin-1beta, interleukin-8 and tumor necrosis factor-alpha in serum of healthy individuals.

Components of biological variation can be used to assess the usefulness of reference values, to evaluate the significance of changes in serial results from an individual and to define objective analytical goals. The aim of the study was to assess, in 15 healthy subjects studied at regular monthly intervals over a period of 6 consecutive months, the biological variation of interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha). Biological variation data (within-subject and between-subject coefficient of variation (CV)) were determined using a simple nested analysis of variance. Derived parameters (index of individuality, reliability coefficient and critical diferences) were calculated from within-subject and between-subject CV. The mean and standard deviation (SD), within-subject CV, between-subject CV, index of individuality and reliability coefficient were as follows: for IL-1beta, 0.67 (0.32) pg/ml, 30%, 36%, 0.85, and 0.76; for IL-8, 3.68 (1.45) pg/ml, 24%, 31%, 0.85 and 0.75; and for TNF-alpha, 3.14 (1.87) pg/ml, 43%, 29%, 1.56 and 0.50, respectively. We conclude that between-subject variation and within-subject variation are quite similar for IL-1beta and IL-8 and are relatively high for the three cytokines studied. Index of individuality is less than 1.4 for IL-1beta and IL-8, and thus reference intervals based on population studies are of limited value. On the contrary, the index of individuality for TNF-alpha is greater than 1.4 and reference values can be used for diagnosis. Quality goals for imprecision are easily achieved for the three cytokines with current methodology.

Femoral prosthetic heads and their significance in polyethylene wear.

We used scanning electron microscopy to perform an ultrastructural analysis and two optical interferometric profilers to measure roughness on 40 prosthetic femoral heads. We expressed roughness as Ra (roughness average) value and Rsk (roughness skewness) value. Our results show that in order to obtain an ideal surface finish a low or not very high Ra value and a negative Rsk value are needed. The presence of depressions or holes (rather than scratches) with smooth (rather than sharp) edges seems to improve the lubrication and wettability properties.

Biological variation of interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL2R) in serum of healthy individuals.

The biological variation of interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL2R), measured by automated enzyme immunoassay, in fifteen subjects studied at regular monthly intervals over a period of 6 consecutive months was measured. The mean and standard deviation (SD), within-subject CV, between-subject CV, individuality index (II) and reliability coefficient (R) were as follow: for sIL2R 571 (231) U/ml, 5.84%, 38.81%, 0.21 and 0.93; and for IL-6 1.43 (0.9) pg/ml, 48.48%, 39.38%, 1.44, and 0.37. The data indicate a relatively high between-subject CV, quite similar in both cases, and a within-subject CV much higher for IL-6 than for sIL2R. Thus, reference values can be used for diagnosis for IL6 (high II), while not for sIL2R (low II). However, the low R for IL-6 implies that more than one measurement are needed. sIL2R has a very high R and a relatively small critical differences, a circumstance appropriate for follow-up.

[The self-measurement of blood glucose and mean glycemias in patients with diabetes mellitus]. / Automedición de la glucosa sanguínea y media de glucemias en pacientes con diabetes mellitus.

OBJECTIVE: To assess the influence that self-measurement of capillary blood glucose (SMBG) has on glucaemia control in patients with diabetes mellitus. DESIGN: Quasi-experimental before and after study. SETTING: Semi-urban health centre. PATIENTS: All diabetic patients, with at least two years of evolution, who used reactive strips for SMBG in 1996. MEASUREMENTS AND MAIN RESULTS: Mean values of base glucaemia in the SMBG study year were compared with those of the year before in 85 patients, 33 men and 52 women, with average age 62.38. Thirteen were type 1 and 72 type 2 diabetics, with a mean 15.61 years of evolution of the disease. A drop of -11.47 mg/dl (SD 44.32) was observed, which was significant (p < 0.05, CI 95%) in the overall results. In all the subgroups, except those treated with non-pharmacological measures, there were drops, ranging between -2.17 mg/dl and -17.01 mg/dl, which were significant in women, in patients with type 2 diabetes, in those who had received health education and in those treated with non-pharmacological measures plus insulin. CONCLUSIONS: Despite the limitations of this kind of study, our findings point towards a slightly better control of glucaemia levels in diabetic patients after SMBG. It is very doubtful whether it signifies any real improvement in managing the illness.

Current databases on biological variation: pros, cons and progress.

A database with reliable information to derive definitive analytical quality specifications for a large number of clinical laboratory tests was prepared in this work. This was achieved by comparing and correlating descriptive data and relevant observations with the biological variation information, an approach that had not been used in the previous efforts of this type. The material compiled in the database was obtained from published articles referenced in BIOS, CURRENT CONTENTS, EMBASE and MEDLINE using "biological variation & laboratory medicine" as key words, as well as books and doctoral theses provided by their authors. The database covers 316 quantities and reviews 191 articles, fewer than 10 of which had to be rejected. The within- and between-subject coefficients of variation and the subsequent desirable quality specifications for precision, bias and total error for all the quantities accepted are presented. Sex-related stratification of results was justified for only four quantities and, in these cases, quality specifications were derived from the group with lower within-subject variation. For certain quantities, biological variation in pathological states was higher than in the healthy state. In these cases, quality specifications were derived only from the healthy population (most stringent). Several quantities (particularly hormones) have been treated in very few articles and the results found are highly discrepant. Therefore, professionals in laboratory medicine should be strongly encouraged to study the quantities for which results are discrepant, the 90 quantities described in only one paper and the numerous quantities that have not been the subject of study.

Acid-base disturbances in the rabbit during experimental hepatic parasitosis.

Acid-base disturbances were examined during experimentally induced infection in the rabbit with Eimeria stiedai, a parasite that profoundly modifies liver morphology and physiology, resulting in anatomical and functional alterations similar to those appearing in different human hepatic diseases. Over 28 days of infection, bicarbonate and lactate concentrations, partial pressures of O2 and CO2, and pH values were determined in the blood and bile of infected animals and compared with the values obtained in noninfected rabbits. The plasma activity of several liver-indicator enzymes was also evaluated. Under our experimental conditions we observed an uncompensated metabolic acidosis that developed with elevated levels of lactate and reduced concentrations of bicarbonate in blood and bile and tended to be compensated by respiratory and biliary mechanisms.

Olive oil- and sunflower oil-fried sardines in the prevention of rat hypercholesterolemia.

The effect of diets containing olive-oil-fried sardines (diet 1) or sunflower-oil-fried sardines (diet 3) upon the serum cholesterol-raise induced by dietary cholesterol was studied after a 4-week experiment in growing Wistar rats. Results of diet 1 were compared to those obtained in diets containing casein plus olive oil (diet 2), whereas results of diet 3 were compared to those obtained with casein plus sunflower oil (diet 4). All diets contained cholesterol and bovine bile as a cholesterol-raising agent. The hypercholesterolemic effect of dietary cholesterol in fried-sardine groups (a total cholesterol (TC) increase of 0.9 mmol/L (p < 0.05 and 0.4 mmol/L (not significant) in groups 1 and 3, respectively) was markedly lower than in groups 2 and 4 (a TC increase of 13.9 mmol/L (p < 0.01) and 18.2 mmol/L (p < 0.01), respectively). Serum triglyceride levels decreased in fried-sardine diets (p < 0.05) while they increased in casein diets (p < 0.05). HDL-cholesterol levels appear lower in diet 1 than in diet 2 (p < 0.05), but similar in diets 3 and 4. However, HDL-fraction carries in diets 1, 2, 3 and 4, 13%, 4%, 53% and 5% of TC, respectively. Results showed that fried-sardine diets exert a powerful check effect on the cholesterol-raising effect induced by dietary cholesterol.

Inhibition of biliary lipid and protein secretion by cyclosporine A in the rat.

We investigated the effect of cyclosporine A (CyA) administered as a single i.v. dose of 20 and 40 mg/kg body wt, on biliary secretion of cholesterol, phospholipid, bile acid, and lysosomal marker and canalicular plasma membrane marker enzymes in anaesthetized Wistar rats. CyA reduced the concentration and biliary secretion of cholesterol, phospholipid and bile acid to a considerable extent; the inhibitory effect of CyA on the biliary secretion of phospholipid and bile acid was greater than that on cholesterol. The biliary outputs of acid phosphatase (AcP) and gamma-glutamyltransferase (gamma-GT) were also diminished by the drug, all these effects being dose-dependent. Maximum decreases in bile acid secretion were observed 10 min after administration, whereas those of cholesterol and phospholipid were delayed. Bile acid concentrations and secretion returned to pretest values at 30-50 min after CyA injection whereas those of cholesterol and phospholipid remained significantly reduced at this time point. The greater inhibitory effect of CyA on the biliary outputs of phospholipid and bile acid relative to cholesterol secretion together with the asynchronous fall and recovery of bile acid, cholesterol and phospholipid concentrations and secretion alter the cholesterol/bile acid, phospholipid/bile acid and cholesterol/phospholipid molar ratios as well as the lithogenic index, thus suggesting that CyA would uncouple biliary lipid secretion from bile acid secretion. Since under physiological conditions biliary lipid and gamma-GT secretion is related to and dependent upon bile acid secretion, we propose that the CyA-induced inhibition on lipid and gamma-GT secretion is, at least partly, secondary to the fall in bile acid output caused by the drug. However, since CyA inhibits secretory processes independent of the hepatobiliary flux of bile acid, such as the exocytic discharge of AcP, and because it also uncouples biliary lipid from bile acid secretion, other mechanisms and factors involved in lipid and protein secretion (such as intracellular transport, canalicular membrane fluidity and/or intracanalicular events) might also be altered by this drug.

Inhibition of biliary cholesterol and phospholipid secretion by cefmetazole. The role of vesicular transport and of canalicular events.

A number of organic anions selectively inhibit the biliary secretion of cholesterol and phospholipids without affecting bile acid secretion. We studied the effect of cefmetazole, a third-generation cephalosporin, on biliary lipid secretion in the rat. Injection of cefmetazole at a dose of 200 mumol/kg body wt. induced a choleretic effect and a significant decrease in the biliary output of cholesterol and phospholipid, without changes in bile acid secretion. The decrease was more marked for cholesterol than for phospholipid secretion, with a significant decrease in their molar ratio in bile. The effects were apparently unrelated to an inhibition of intracellular vesicular transport because, after injection of horseradish peroxidase, both the time course and total amount secreted of the protein did not significantly differ between control animals and those receiving cefmetazole. The secretory rate of the lysosomal marker acid phosphatase was not affected by cefmetazole administration. Biliary outputs of the plasma-membrane enzymes alkaline phosphatase and gamma-glutamyltransferase were significantly decreased by the antibiotic. These results point to an effect of cefmetazole at the level of the canalicular membrane.