Diagnostic accuracy of the anion gap to identify toxic lithium concentrations: a single-center retrospective observational study.

INTRODUCTION: Lithium exhibits a narrow margin between therapeutic doses and toxic blood concentrations, which can pose a substantial risk of toxic effects. Reportedly, lithium toxicity may be associated with a reduced anion gap; however, the precise relationship remains unclear. This study examined several different anion gap calculation methods to detect toxic lithium concentrations without directly measuring blood lithium concentrations. METHODS: Our retrospective study analyzed blood samples collected for lithium concentration measurements. The anion gap was determined using three different methods, both with and without albumin and lactate concentration corrections. Samples were categorized into two groups based on lithium concentration (<1.5 or ≥1.5 mmol/L), and anion gap values were compared. Correlation and logistic regression analyses were used to assess the relationship between each anion gap indicator and lithium concentration. Receiver operating characteristic curves were used for diagnostic analysis. RESULTS: Overall, 24 measurements were collected, with 41.7% of samples falling within the toxic range. The high-lithium concentration group exhibited significantly smaller anion gaps. Correlation and logistic regression analyses revealed a significant association between anion gap values and lithium concentrations. Areas under the receiver operating characteristic curve were: conventional anion gap 0.77 (95% CI: 0.55-0.94); albumin-corrected anion gap 0.85 (95% CI: 0.66-1.00); and both albumin- and lactate-corrected anion gap 0.86 (95% CI: 0.66-1.00). DISCUSSION: The anion gap is calculated as the difference between measured cations and anions. Accumulation of lithium (a cation) may decrease measured cations and decrease the calculated anion gap. Abnormal albumin and lactate concentrations may also alter the anion gap and affect its usefulness as a diagnostic marker for elevated serum lithium concentrations. A negative likelihood ratio of 0.1 suggests that the anion gap might be valuable in excluding toxicity. CONCLUSIONS: The corrected anion gap, accounting for albumin and lactate concentrations, may be beneficial in suggesting the possibility of toxic lithium concentrations.

Sonochemical synthesis of graphene oxide-Ag2O nanozyme as an oxidize-like mimic for the highly sensitive detection of lithium in blood serum.

Bipolar disorder is commonly treated with lithium carbonate. The concentration of lithium in the blood serum should be closely monitored in patients who require long-term lithium therapy. To date, no colorimetric method of detecting lithium ions has been reported using nanosensors. We have developed a novel chemosensor based on nanozyme (NZ) to address this clinical need. The GO-Ag2O NZs were synthesized by a sonochemical method and used as a colorimetric nanosensor to detect lithium ions in human blood serum (Li (I)). To characterize NZs, various techniques were employed, including XRD, FTIR, TEM, FESEM, EDX, Raman spectroscopy, BET, DLS, Zeta potential, and ICP-OES. According to TEM and FESEM images of GO-Ag2O, the nanoparticles (NPs) of Ag2O are uniformly distributed on the surface of 2D graphene oxide sheets. In addition, silver oxide nanoparticles exhibited a cubic morphology with an average size of 3.5 nm. We have examined the performance of the NZs in an aqueous medium and in human blood serum that contains Li (I). A colorimetric test revealed that NZs synthesized in the presence of ultrasound were more sensitive to Li (I). According to the linearity of the calibration curves' ranges, Li (I) has a limit of detection (LOD) of 0.01 µg/mL. Furthermore, it displayed a linear range between 0 and 12 µg/mL. GO-Ag2O NZs showed noticeable color changes from green to orange after exposure to Li (I). An incubation time of two minutes was found to be the most effective for sensing. This innovative approach provides a reliable method for monitoring lithium levels and ensuring patient safety during long-term lithium therapy for bipolar disorder.

Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study.

ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

Novel sample double dilution calibration method for determination of lithium in biological samples using automatic flow system with in-syringe reaction.

A novel sample double dilution calibration method (SDDCM) and an automatic flow system with in-syringe reaction and spectrophotometric detection were developed for determining lithium in biological samples. The method is based on the reaction of lithium with Thorin in an alkaline medium and the signal was measured at 480 nm. The reaction was performed simultaneously for both standards and samples in three syringes of the automatic flow system. The method was validated and successfully applied to the determination of lithium in synthetic and pharmaceutical samples, with results consistent with the ICP OES method. The novel calibration method, developed for the determination of lithium in biological samples, uses a sample with two dilution degrees. Using the method, the concentration of the analyte is determined by relating the signal for a less diluted sample to the calibration plot for a more diluted sample and vice versa. The implementation of the calibration method was facilitated by preparing solutions directly in the flow system. The use of two sample dilutions makes it possible to determine the analyte in the sample without preliminary preparation. Moreover, obtaining two results based on signals for a sample diluted to different degrees allows them to be verified for accuracy. The proposed approach was successfully verified by the determination of lithium in certified reference materials of blood serum and urine. Using the developed method lithium was determined within the concentration range of 0.06-1.5 mg L-1, with precision (CV, %) less than 6.7, and accuracy (RE, %) better than 6.9. The detection limit was 0.03 mg L-1.

Dried Blood Spots and Miniaturized Ultrasonic Nebulization Microplasma Optical Emission Spectrometry for Point-of-Care Testing of Blood Lithium.

Despite the significant importance of blood lithium (Li) detection in the treatment of bipolar disorder (BD), its point-of-care testing (POCT) remains a great challenge due to tedious sample preparation and the use of large-footprint atomic spectrometers. Herein, a system coupling dried blood spots (DBS) with a point discharge optical emission spectrometer equipped with a miniaturized ultrasonic nebulizer (MUN-µPD-OES) was developed for POCT of blood Li. Three microliters of whole blood were used to prepare a dried blood spot on a piece of filter paper to which 10 µL of eluent (1% (v/v) formic acid and 0.05% (v/v) Triton-X) was added. Subsequently, the paper was placed onto the vibrating steel membrane of the ultrasonic nebulizer and powered on to generate aerosol. The aerosol was directly introduced to the µPD-OES for quantification of Li by monitoring its atomic emission line at 670.8 nm. The proposed method minimized matrix interference caused by high levels of salts and protein. It is worth noting that the MUN suitably matches the needs of DBS sampling and can provide aerosolized introduction of Li into the assembled µPD-OES, thus eliminating all tedious sample preparation and the need for a commercial atomic spectrometer. Calibration response is linear in the therapeutic range and a limit of detection (LOD) of 1.3 µg L-1 is well below the Li minimum therapeutic concentration (2800 µg L-1). Li in mouse blood was successfully detected in real-time using MUN-µPD-OES after intraperitoneal injection of lithium carbonate, confirming that the system holds great potential for POCT of blood Li for patients with BD.

Determination of lithium in the blood of the deceased by inductively coupled plasma mass spectrometry in a case of lithium-ion battery fire.

In this study, a case of lithium-ion battery fire is presented. The blood of the deceased was analyzed for lithium (Li) using ICP-MS (inductively coupled plasma mass spectrometry). When compared to normal individuals in the same region, the deceased had much higher levels of Li in their blood. Therefore, conducting quantitative analyses of Li in the bodies of individuals who die in lithium-ion battery fire can provide valuable information into the specific circumstances surrounding their deaths.

Existing and Emerging Technologies for Therapeutic Monitoring of Lithium: A Scoping Review.

BACKGROUND/PURPOSE: Lithium is an effective psychoactive drug. It has a narrow therapeutic margin, with subtherapeutic levels or intoxication commonly occurring. Therapeutic drug monitoring (TDM) of lithium has several barriers. This scoping review aims to describe and analyze existing and emerging technologies for lithium TDM and to describe the lithium quantification parameters (precision, accuracy, detection limit) attributed to each technology. METHOD: PubMed, Scopus, Web of Science, and Google Scholar were searched. Studies that described lithium quantification and complied with PRISMA-ScR guidelines were included. Articles selection was conducted by 2 researchers. Good precision was defined if its relative standard deviation <3%; acceptable, from 3% to 5%; and low, >5%. Accuracy was considered good if the error <5%; acceptable, 5%1 to 0%; and low if it was >10%. RESULTS: Of the 2008 articles found, 22 met the inclusion criteria. Of these, 14 studies concerned laboratory devices, in which precision was found to be low in one third of cases, and half had good precision. Accuracy of one third was good, another third was low, and the remaining third did not report accuracy. The other 8 studies concerned portable devices, in which precision was low in more than 60% of the cases and good in 25% of the studies. Accuracy was low in 50% of the cases, and good in just over a third. Limits of detection included the therapeutic range of lithium in all studies. CONCLUSIONS: Among emerging technologies for lithium TDM, precision and accuracy remain a challenge, particularly for portable devices.

Intoxicació per liti en pediatria. Importància de sospitar vies d'absorció de tòxics inusuals / Intoxicación por litio en pediatría. Importancia de las vías inusuales de absorción / Lithium poisoning in children. The importance of suspecting unusual paths for absorbing toxics

Introducció: La intoxicació per liti en pediatria és infreqüent i pot arribar a provocar greus complicacions. Observació clínica: Exposem el cas d'un nen de 35 mesos que presenta somnolència, marxa atàxica i vòmits. En l'exploració física destaca tendència a la son i marxa atàxica, i en l'otoscòpia esquerra s'observen abundants secrecions que dificulten la visualització del timpà. Es realitza tomografia axial computada cranial, que confirma la presència al conducte auditiu extern esquerre d'un cos estrany esfèric d'uns 6 mm de diàmetre i densitat metàl·lica. El cos estrany s'extreu sota anestèsia, i es constata que és una pila de botó amb signes de degradació. La litèmia confirma nivells elevats (0,2 mmol/L). Després de l'extracció del cos estrany, el pacient presenta una evolució favorable, amb remissió de la simptomatologia ad integrum. Comentaris: Davant de la clínica neurològica tòrpida no es pot obviar la possibilitat d'una intoxicació. El nostre cas clínic exemplifica aquest tipus de patologia, tenint en compte que es tracta d'una intoxicació infreqüent, tant pel tipus de tòxic, com per la via d'absorció, la localització i el temps d'evolució

Introducción: La intoxicación por litio en pediatría es infrecuente y puede llegar a producir graves complicaciones. Observación clínica: Exponemos el caso de un niño de 35 meses que presenta somnolencia, marcha atáxica y vómitos. En la exploración física destaca tendencia al sueño y marcha atáxica, y en la otoscopia izquierda se observan abundantes secreciones que dificultan la visualización del tímpano. Se realiza tomografía axial computerizada craneal, que confirma la presencia en el conducto auditivo externo izquierdo de un cuerpo extraño esférico de unos 6 mm de diámetro y densidad metálica. El cuerpo extraño se extrae bajo anestesia, y se constata que es una pila de botón con signos de degradación. La litemia confirma niveles elevados (0,2 mmol/L). Tras la extracción del cuerpo extraño, el paciente presenta una evolución favorable, con remisión de la sintomatología ad integrum. Comentarios: Ante la clínica neurológica tórpida, no se puede obviar la posibilidad de una intoxicación. Nuestro caso ejemplifica este tipo de patología, teniendo en cuenta que se trata de una intoxicación infrecuente, tanto por el tipo de tóxico, como por la localización y el tiempo de evolución

Introduction: Lithium poisoning in children is rare and can result in severe toxicity. Clinical observation: We report the case of a 35-month-old child who presented with drowsiness, unstable gait, and vomiting. Physical examination revealed somnolence and ataxia. A left otoscopy examination revealed abundant fluid in the ear canal and poor visualization of the tympanic membrane. Cranial computerized tomography reported the presence of a 6 mm round foreign body of metal density lodged in the left external auditory canal. A lithium button cell battery with signs of degradation was extracted. Laboratory evaluation showed elevated lithemia (0.2 mmol/L). Following the extraction of the foreign body, the patient showed progressive improvement, with eventual complete resolution of all signs and symptoms of lithium poisoning. Comments: Lithium poisoning should be considered in the differential diagnosis of sudden onset of non-specific neurological abnormalities. Our case exemplifies the rarity of this type of poisoning, considering the toxin, the absorption pathway, the location of the source of the poison, and the time of evolution

Compromiso de conciencia secundario a intoxicación por litio: reporte de un caso / Commitment of conscience secondary to lithium intoxication: case report

INTRODUCCIÓN: La intoxicación por litio (IL) es potencialmente grave. Destacan manifestaciones neurológicas, tales como deterioro cognitivo, síndrome cerebeloso y compromiso de conciencia (CC). En la literatura se han descrito secuelas permanentes secundarias a la IL, siendo importante el manejo precoz para prevenir una evolución tórpida de este cuadro. PRESENTACIÓN DEL CASO: Paciente de sexo femenino de 77 años con antecedentes de Trastorno Afectivo Bipolar (TAB), en tratamiento con Litio, inició cuadro de 5 días de evolución caracterizado por bradipsiquia, compromiso del estado general (CEG) y disminución de fuerza en extremidades inferiores. Evaluada por Neurología, se descartó patología cerebrovascular e infecciosa intercurrente, se midió litemia que resultó alterada. Se diagnosticó CC secundario a IL. Se indicó suspensión de fármaco y manejo de balance hidroelectrolítico. Evolucionó con daño neurológico de pronóstico incierto y fue dada de alta por Neurología. DISCUSIÓN: La intoxicación por litio debe sospecharse en cualquier paciente con alteración del estado de conciencia basal, que sea usuario de este medicamento. Pacientes que presentan IL requieren hospitalización para manejo de fluidos y electrolitos, monitorizando función renal y litemia. A nivel del sistema nervioso central (SNC) la IL puede dejar secuelas irreversibles, por lo que se recomienda un seguimiento regular de aquellos pacientes que sean usuarios de este medicamento, para evitar un deterioro clínico secundario a una intoxicación.

INTRODUCTION: (LI) can be potentially serious. Includes neurological manifestations such as cognitive impairment, cerebellar syndrome and compromise of consciousness (CC). In the literature have been described permanent sequelae secondary to intoxication by this drug, early management is important to prevent an undesirable evolution of this medical condition. CASE REPORT: 77-year-old female patient with a history of Bipolar Affective Disorder, under treatment with Lithium, began a 5-day history of bradypsychia, compromise of the general state and decrease strength in lower extremities. Evaluated by Neurology, ruled out cerebrovascular and infectious pathologies. Plasmatic lithium levels were obtained in altered range. CC secondary to LI was diagnosed. Drug suspension, fluid and electrolyte balance management were indicated. She evolved with neurological damage of uncertain prognosis and discharged from hospital. DISCUSSION: LI should be suspected in any patient with altered baseline consciousness, who is a user of this medication. Patients requires admission for fluid and electrolyte management, monitoring of renal function and plasmatic lithium levels. At the level of the central nervous system (CNS) IL can leave irreversible sequels, so it is recommended a regular monitoring of patients who are users of this drug, to avoid clinical deterioration secondary to intoxication.

Tratamiento de la intoxicación aguda por litio mediante hemodiálisis con dializadores de alta eficiencia / Treatment of acute lithium intoxication wigh high-flux haemodialysis membranes

El carbonato de litio se utiliza de forma habitual para el tratamiento de los trastornosbipolares (maniaco-depresivos). Sin embargo, debido a su estrecho margenterapéutico la elevación de los niveles séricos, bien durante la terapia crónica demantenimiento o después de una sobredosis aguda, puede dar lugar a toxicidadgrave. En la intoxicación aguda severa por litio el tratamiento establecido es la hemodiálisis,que permite la eliminación rápida de la droga. Las membranas de altoflujo deben ser capaces de eliminar más litio por hora de hemodiálisis, pero existenpocas evidencias al respecto. Se presentan tres pacientes con una intoxicaciónaguda por litio con riesgo vital, complicada en dos de ellos por insuficiencia renal,que fueron tratados con éxito mediante hemodiálisis intermitente diaria con membranasde alto flujo. Las técnicas actuales de hemodiálisis, utilizando dializadoresde alta eficiencia y baño de diálisis con bicarbonato, permiten una eliminaciónexcelente del litio sin el rebote que típicamente se observaba en el pasado tras lahemodiálisis convencional. La hemodiálisis debe ser instaurada precozmente encualquier paciente con intoxicación por litio que presente coma, convulsiones, fallorespiratorio, deterioro del estado mental, y especialmente si la función renal estácomprometida

Lithium carbonate is commonly prescribed for the treatment of bipolar(manic-depressive) disorders. However, because of its narrow therapeutic indexan excessive elevation of serum lithium concentration, either during chronicmaintenance therapy or after an acute overdose, can result in serious toxicity.In addition to supportive care, the established treatment of severe lithium toxicity is haemodialysis. Conventional haemodialysis can reduce serum lithiumrapidly, but post-dialysis rebound elevations with recurrent toxicity have beendocumented in old publications. High-flux membranes should be capable ofremoving more lithium per hour of haemodialysis, but published values are notavailable. We report here three patients with acute lithium intoxication whowere treated successfully with bicarbonate and high-flux haemodialysis membranes.Our patients presented with a severe degree of intoxication, based onthe amount of drug ingested, the initial serum lithium level, the severity of neurologicsymptoms and systemic manifestations. Two patients developed acuterenal failure probably as a result of volume depletion since it was rapidly reversibleby haemodialysis and infusion therapy. In addition, consecutive haemodialysissessions and improvement of renal function allowed a rapid decreasein serum lithium levels without haemodynamic instability or reboundelevations in lithium concentration. The effectiveness of the procedure in thesecases can be attributed to the use of bicarbonate dialysate and high-efficiencydialysers. This is the first report describing the effect of high-efficiency dialyserson lithium pharmacokinetic. Using this technique the elimination rate oflithium was found to be greater than previously reported with haemodialysis

Efeitos da intoxicação por lítio sobre a locomoção de ratos em um modelo animal de insuficiência renal aguda cirurgicamente induzido / Effects of lithium toxicity on rat locomotion in an animal model of surgical induced acute of kidney failure

INTRODUÇÃO: O lítio é um metal usado sob a forma de sal para tratamento de episódios agudos de mania e no controle profilático de desordens afetivas bipolares. Pacientes com algum grau de insuficiência renal podem rapidamente sofrer intoxicação por esse fármaco. Nosso objetivo foi verificar a influência da litemia na locomoção em um modelo animal cirurgicamente induzido de insuficiência renal aguda (IRA). MÉTODOS: Foram submetidos 61 ratos Wistar a tratamento com lítio por uma semana previamente a nefrectomia unilateral. Trinta ratos foram induzidos a IRA. Foi administrado lítio ou solução fisiológica aos ratos e após observada sua locomoção e concentração de creatinina sérica. Utilizou-se análise estatítica. RESULTADOS: A creatina apresentou-se elevada nos ratos com IRA. A locomoção foi menor nos ratos com IRA que receberam lítio, havendo relação inversa entre a litemia e a atividade locomotora. CONCLUSÕES: O modelo animal cirúrgico de IRA foi efetivo. Ratos insuficientes renais que receberam lítio apresentaram alterações locomotoras comparados aos demais. O aumento da litemia causa diminuição proporcional na locomoção dos ratos.

Tratamiento de la enfermedad bipolar durante el embarazo y puerperio: caso clínico / Treatment of a pregnant patient with a bipolar disorder: clinical case

We report a 37 years old woman with a severe bipolar disorder, that became pregnant during treatment with lithium. The patient and her family were informed about the 0.05-0.1 percent risk of cardiac malformations of the newborn, but decided to maintain her pregnancy and not to discontinue the use of lithium, fearing a relapse of her psychiatric ailment. She continued under medical surveillance and had a normal delivery, but no breast feeding was allowed

Toxicidad de litio inducida por captoprilo. A propósito de un caso / Lithium toxicity induced by captopril. A case report

Se describe un caso de toxicidad por litio con niveles séricos incrementados durante la administración simultánea de captoprilo.Un hombre de 57 años y 70 kg tratado con nifedipino, lisinoprilo y litio fue ingresado por un episodio de ictus. El tratamiento antihipertensivo en la unidad de cuidados intensivos (UCI) incluyó labetalol, nitroprusiato, nifedipino y clonidina. Tras alta en la UCI se interrumpieron labetalol, nitroprusiato y clonidina y se inició tratamiento con captoprilo 50 mg/8 h. Tras cuatro días de tratamiento con captoprilo, la litemia fue de 2,6 mmol/I y el examen del paciente reveló confusión, letargia, mioclonos y marcha atóxica. Se interrumpió el tratamiento con litio y su concentración bajó en las siguientes cuarenta y ocho horas hasta 1,4 mmol/I. Los signos y síntomas del paciente desaparecieron, se estabilizó médicamente y fue dado de alta seis días después de interrumpir el litio. Aunque continúa siendo el tratamiento de elección en el trastorno bipolar, el uso del litio se asocia con un estrecho margen terapéutico. Pequeños incrementos en la concentración sérica pueden inducir graves efectos adversos. En consecuencia, resulta de la máxima importancia la combinación segura del litio con otros fármacos que pueden influenciar su farmacocinética.Se han observado incrementos en la litemia tras la introducción de inhibidores de la enzima convertidora de angiotensina (ECA). Este efecto parece secundario al incremento en la natriuresis asociada con los efectos antagonistas de la aldosterona mediados por los inhibidores de la ECA. Los clínicos tenemos que prestar especial atención a esta interacción potencialmente grave. La litemia tiene que monitorizarse si los pacientes que reciben litio son tratados con captoprilo (AU)

Dosagem de Lítio: Alerta / Lithium; Lithium`s serum level

A partir da observaçäo de incoerências entre dados clínicos e resultados laboratoriais, os autores formularam a hipótese de que a mensuraçäo sérica de Lítio pode näo ser confiável em pelo menos alguns laboratórios. Coletaram-se amostras de sangue de dez pacientes internados portadores de distúrbio bipolar e em tratamento com carbonato de Lítio. Foram realizadas dosagens séricas de Lítio de cada amostra em cinco laboratórios. Encontraram-se discrepâncias significativas entre os resultados das dosagens. Os resultados sugerem que as dosagens séricas de Lítio em pelo menos alguns laboratórios estäo sujeitas a variaçöes clínicamente significativas. Recomenda-se a realizaçäo de estudos mais abrangentes para se avaliar a extensäo do problema

Reduced renal sodium excretion in walker-256 tumor-bearing rats

Subcutaneous inoculation of Walker-256 tumor is followes by an asymptomatic period which is widely variable in duration, after which, paraneoplastic effects appear suddenly in the form of progressive and rapidy changing homeostatic alterations. Multifocal inoculation of tumor cells in each animal, was carried out with data averaging in each (sub-clinical [SubC], moderate [mCP] and grave [gCP] clinical phases and compared to foodrestrieted FR. The renal sites involved were studied in awake unrestrained animals by measure of sodium, cratinine and lithium clearance. Results indicated an initial increase of both absolute proximal (mCP:21.4+1.7 vs FR: 16.0+1.1 mmol/min/100 g.b.w., p<0.05) and postproximal (mCP:11.1+0.4 vs FR:6.6+0.4 mmol/min/100g g.b.w., p<0.001) Na+ reabsorption, which were partially compensated by a rise in glomerular filtration rate (mCP:213+11.4 vs FR: 162+10.2p1/min/100 g.b.w., p<0.01) and by fell of fractional proximal Na+ reabsorption (mCP:62.8+ vs FR: 70.1+1.7 per cent, p<0.05), despite this a significant Na+ and fluid retention was observed. Additionally, this study shows that terminal phase of the illness (gCP) culminated with a marked decrease in the creatinine clearance suggesting a significant fall of the renal function. (AU)

Reduced renal sodium excretion in walker-256 tumor-bearing rats

Subcutaneous inoculation of Walker-256 tumor is followes by an asymptomatic period which is widely variable in duration, after which, paraneoplastic effects appear suddenly in the form of progressive and rapidy changing homeostatic alterations. Multifocal inoculation of tumor cells in each animal, was carried out with data averaging in each (sub-clinical [SubC], moderate [mCP] and grave [gCP] clinical phases and compared to foodrestrieted FR. The renal sites involved were studied in awake unrestrained animals by measure of sodium, cratinine and lithium clearance. Results indicated an initial increase of both absolute proximal (mCP:21.4+1.7 vs FR: 16.0+1.1 mmol/min/100 g.b.w., p<0.05) and postproximal (mCP:11.1+0.4 vs FR:6.6+0.4 mmol/min/100g g.b.w., p<0.001) Na+ reabsorption, which were partially compensated by a rise in glomerular filtration rate (mCP:213+11.4 vs FR: 162+10.2p1/min/100 g.b.w., p<0.01) and by fell of fractional proximal Na+ reabsorption (mCP:62.8+ vs FR: 70.1+1.7 per cent, p<0.05), despite this a significant Na+ and fluid retention was observed. Additionally, this study shows that terminal phase of the illness (gCP) culminated with a marked decrease in the creatinine clearance suggesting a significant fall of the renal function.

Chronic but not acute Li+ treatment prevents behavioral depression in rats

The effect of lithium administration on the learned hellessness model of depression was investigated. Female Wistar rats (190-210g) received either tap water alone (N=156) or 20 mM LiCL, provided chronically (30 days; N = 127) or acutely (5 days; N = 22), in the drinking water. Three days before the end od treatment, each group was divided into two subgroups which received either inescapable shock (IS) or no shock (NS) treatment in shuttle boxes. All groups were subsequenty submitted to an escape test on the following day and then sacrificed one day after the escape test, when blood samples were taken to measure serum Li+, Na+ and K+ concentrations by flame photometry. There were no significant differences in serum Na+ amongst the 4 groups. chronically treated NS and IS rats both presented an increase in serum K+ compared to the control rats. The IS and not the NS chronically treated rats presented increased serum Li+ levels which cannot be accounted for in terms of differences in Li+ intake. The IS group treated chronically with lithium had a better escape performance than the IS group receiving either tap water or acute Li+ administration. We conclude that chronic but not acute Li+ treatment at a serum level within the prophylactic range (0,5 mEq) is able to prevent learned helplessness in the rat. These results agree with the data obtained in clinical practice indicating that li+ is only effective after chronic administration and that Li+ - induced hyperkalemia is a side effect