Intoxicación por ácido acetilsalicílico, fisiopatología y manejo / Physiopathology and management of acetylsalicylic acid intoxication

Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.

Blood electrolyte disturbances during severe hypoglycemia in Korean patients with type 2 diabetes

BACKGROUND/AIMS: To investigate abnormalities in blood electrolyte levels during severe hypoglycemia in Korean patients with type 2 diabetes mellitus (T2DM) in a clinical setting. METHODS: Blood electrolyte levels in adult T2DM patients during severe hypoglycemia were collected from January 1, 2008 to December 31, 2012. Patients who maintained normal serum creatinine and blood urea nitrogen levels were utilized in the study. Severe hypoglycemia was defined as a condition requiring medical assistance, such as administering carbohydrates when serum glucose levels less than 70 mg/dL were observed, in conjunction with other symptoms of hypoglycemia. RESULTS: A total of 1,068 patients who visited the emergency room with severe hypoglycemia were screened, of which 219 patients were included in this study. The incidence of abnormal levels for any electrolyte was 47%. Hypokalemia ( 100 beats per minute) and severe hypertension (> or = 180/120 mmHg) were 30 mg/dL (range, 14 to 62) and 35 mg/dL (range, 10 to 69; p = 0.04), 18.8% and 7.2% (p = 0.02), and 20.8% and 10.2% (p = 0.05) in the hypokalemia and normokalemia groups, respectively. CONCLUSIONS: During severe hypoglycemia, hypokalemia occurred in 21.9% of T2DM patients and was associated with tachycardia and severe hypertension. Therefore, the results suggest that severe hypoglycemia may increase cardiovascular events in T2DM.

Diuretic effect of powdered Cerasus avium [cherry] tails on healthy volunteers

In this study, the diuretic activity of powdered cherry stalk was evaluated in 13 healthy volunteers by means of their water balance. In addition to biochemical parameters, such as urinary electrolyte concentration, osmolality and any adverse reaction were determined. The capsules of cherry stalks were administered at an equivalent dose of 2.0 grams of the plant per person. Urinary biochemical determination was made of concentration of electrolytes [sodium, potassium, chloride and calcium], urinary volume and osmolality by standard laboratory procedures. Statistical evaluation was performed by Student's-t and Wilcoxon rank tests. After administration of cherry stalk, the mean of urine calcium, sodium, chloride, and urine volume increased, but the amount of urine potassium and urine osmolality did not change. No adverse reaction was observed. Powdered C. avium stalk increased mild urine volume confirming thus the claimed diuretic effect of the herb. Administration of cherry stalk caused urinary sodium and chloride rising less than loop diuretics but higher than the others. Because of rising calcium excretion, it should be used with cautious in those with urolithiasis

Experimental antegrade enema: effects on water, electrolyte and acid-base balances with different solutions

PURPOSE: To study the effects on the water, electrolyte, and acid-base balances in rabbits submitted to antegrade enema with different solutions through appendicostomy. METHODS: Forty male New Zealand rabbits were submitted to appendicostomy, and distributed in 4 groups, according to the antegrade enema solution: PEG group, polyethylene glycol electrolyte solution (n=10); ISS group, isotonic saline solution (n=10); GS group, glycerin solution (n=10); SPS group, sodium phosphate solution (n=10). After being weighed, arterial blood gas analysis, red blood count, creatinine and electrolytes were measured at 4 times: preoperatively (T1); day 6 postop, before enema (T2); 4h after enema (T3); and 24h after T3 (T4). RESULTS: In PEG group occurred Na retention after 4h, causing alkalemia, sustained for 24h with HCO3 retention. In ISS group occurred isotonic water retention and hyperchloremic acidosis after 4h, which was partially compensated in 24h. GS group showed metabolic acidosis after 4h, compensated in 24h. In SPS group occurred hypernatremic dehydration, metabolic acidosis in 4h, and hypokalemia, hypocalcemia, hypomagnesemia, and metabolic alkalosis with partially compensated dehydration in 24h. CONCLUSIONS: All solutions used in this study caused minor alterations on water, electrolyte or acid-base balances. The most intense ones were caused by hypertonic sodium phosphate solution (SPS) and isotonic saline solution (ISS) and the least by polyethyleneglycol electrolyte solution (PEG) and glycerin solution 12 percent (GS).

OBJETIVO: Estudar os efeitos no equilíbrio hídrico, eletrolítico e ácido-base, do enema anterógrado com diferentes soluções em coelhos através de apendicostomia. MÉTODOS: 40 coelhos Nova Zelândia, machos, submetidos a apendicostomia, distribuídos em quatro grupos segundo a solução de enema: grupo PEG (n = 10) solução de polietilenoglicol com eletrólitos; grupo SF (n = 10) solução fisiológica; grupo SG (n = 10) solução glicerinada; grupo FS (n = 10) solução de fosfato de sódio. Realizou-se pesagem, gasometria arterial, série vermelha, creatinina e ionograma, em quatro tempos: TI (pré-operatório); T2 (6o PO antes do enema); T3 (4h após enema); T4 (24h após T3). RESULTADOS: No PEG ocorreu retenção de Na em 4h, com alcalemia por retenção de HCO3, mantida por 24h. No SF ocorreu retenção hídrica isotônica e acidose hiperclorêmica em 4h, resolvidos parcialmente com 24h. No SG ocorreu acidose metabólica hiperclorêmica em 4h, compensada com 24h. No FS ocorreu desidratação hipenatrêmica, acidose metabólica com ânion gap elevado em 4h, hipopotassemia, hipocalcemia, hipomagnesemia e alcalose metabólica com recuperação parcial da desidratação em 24h. CONCLUSÕES: Todas as soluções empregadas neste estudo causam alterações de pouca intensidade no equilíbrio hídrico, eletrolítico ou ácido-base. As mais intensas foram causadas pela solução de fosfato de sódio e solução fisiológica, e as menos intensas pela solução de polietilenoglicol com eletrólitos e solução glicerinada.

Effect of a new oral contraceptive with drospirenone on vital signs, complete blood count, glucose, electrolytes, renal, and liver function.

OBJECTIVE: To evaluate the effect of a new oral contraception formulation with drospirenone (Yasmin) on vital signs, complete blood count, glucose, electrolytes, and renal and liver function. MATERIAL AND METHOD: An open-label non-comparative clinical trial was conducted. One hundred women who were planning to use oral contraception for at least six months were recruited. The subjects received a blister pack which contained 21 tablets of 3 mg drospirenone /30 tg ethinyl estradiol for the first four cycles (1 cycle = 28 days). Cycle 5 and 6 blister packs were dispensed during the visit in cycle 4. Heart rate and blood pressure of each subject were checked at baseline and each visit. Serum from each subject was collected and sent for complete blood count, glucose, electrolytes, and renal and liver function tests at baseline and at cycle 6. Mean differences in these tests at cycle 6 compared to baseline were assessed. RESULTS: Ninety-two of the 100 subjects (92%) completed the present study. There was no significant change in heart rate, blood pressure, complete blood count, glucose, electrolytes, and renal and liver function tests at cycle 6 when compared to baseline. CONCLUSION: Oral contraception formulation with drospirenone (Yasmin) is well tolerated and has good contraceptive efficacy. It is safe, as it has no effect on heart rate, blood pressure, complete blood count, glucose, electrolytes, and renal and liver function.

Sodium transporters in kidney role in health and disease.

Sodium is an important cation and has an important role in BP regulation and ECF balance. Kidney plays an important role in sodium balance. Almost 99% of filtered sodium is reabsorbed. The absorption occurs via sodium transporters located in the various segments of the nephron. Each of these transporters has unique features and is blocked by a specific diuretic. The activating and inactivating mutations of these transporters are associated with important clinical syndromes. The understanding of these transporters and their mutations is essential for proper diagnosis and management of syndromes associated with the defects of these transporters. Also the knowledge of sodium transporters helps in understanding the role of kidney in pathogenesis of hypertension and pharmacodynamics of diuretic action.

Dose related effects of Buspirone on serum electrolyte balance, plasma osmolality and systolic blood pressure [SBP] in rats

Buspirone is a potent anxiolytic that decreases serotonin transmission. Changes in electrolyte balance, plasma osmolality and systolic blood pressure are often associated with stress-induced anxiety in rats as well as in human but effects of buspirone on changes in serum electrolytes balance, plasma osmolality and SBP of rats has not been reported. Present study concerns the effects of different doses of buspirone [0.25, 0.5, and 1mg/kg] on serum electrolyte, plasma osmolality and systolic blood pressure [SBP] of rats. Anxiolysis related variable are also monitored. Results show that the administration of buspirone [0.25mg/kg and 0.5mg/kg] significantly increased the serum concentration of electrolytes and plasma osmolality but decreased the serum level of magnesium. These doses also reduced the systolic blood pressure [SBP]. A dose of 1mg/kg buspirone produced no effect on the concentration of serum electrolytes, and plasma osmolality. Anxiolytic effects of the drug were dose dependent but 1mg/kg dose decreased the effect. The results are discussed in the context of serotonin receptors [5-HT[1A] to be involved in buspirone-induced changes of electrolytes, SBP and plasma osmolality

Exchangeable sodium induced changes in yield, water relation and cation composition of fennel (Foeniculum vulgare Mill).

A pot experiment was conducted with the objectives to assess the adaptation potential of fennel crop grown at 10, 20, 25, 35 and 40 ESP (exchangeable sodium percentage) levels. Results showed that the rate of seed germination, plant growth including branching pattern, umbels per plant and 1000 test seed weight were adversely affected by sodic soils. Assuming that fifty percent reduction in seed yield and Na+/K+ ratio in leaf tissue as an index of alkali tolerance revealed that fennel was tolerant up to 25 ESP. The cell sap pH and EC reflected optimum osmoticum maintenance to withstand sodicity stress at this level and beyond this leaf water potential decreased (negatively) more to impede water uptake.

Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers.

OBJECTIVE: Turmeric extract and turmeric oil have shown chemoprotective effect against chemically-induced malignancies in experimental animals. They can reverse precancerous changes in oral submucous fibrosis in humans. The use of turmeric or Curcuma longa Linn as a spice and household remedy has been known to be safe for centuries. In view of the long term administration required for cancer prevention a Phase I clinical trial of turmeric oil (TO) was designed to study the safety and tolerance of TO in volunteers for a period of 3 months. MATERIAL AND METHODS: Nine healthy volunteers between 20 and 33 years of age were tested for haemoglobin, blood counts, liver and kidney functions, bleeding and clotting time and serum electrolytes initially and at 1 and 3 months of treatment. They were administered 0.6 ml of TO three times a day for 1 month and 1 ml in 3 divided doses for 2 months. The acute tolerability study on Day 1 was conducted in a Clinical Pharmacology daycare Unit. Blood pressure and pulse were recorded frequently on Day 1 and at 24, 48, 72 and 96 hours and fortnightly till 12 weeks. Volunteers were daily supervised for TO intake as well as for any side effects throughout the study period. RESULTS: Nine volunteers were enrolled for the study. One discontinued on 3rd day for allergic skin rashes which, on discontinuation of TO, gradually disappeared by two weeks. Another discontinued on 7th day for intercurrent fever requiring antibiotic treatment. Seven volunteers completed the study. There was no effect of TO, in two doses, on pulse and blood pressure and no side effects in acute tolerability study on Day 1. There was no effect of TO intake on weight, blood pressure, symptoms and signs upto 12 weeks. There was no clinical, haematological, renal or hepatic-toxicity of TO at 1 month and 3 months. Serum lipids did not show significant change except in one volunteer (reversible). CONCLUSIONS: In view of the potential for reversing oral submucous fibrosis, a precancerous condition for oral cancer, TO, can be recommended directly for a Phase II trial in patients.

Soluções hipertônicas em pediatria / Hypertonic solutions for pediatric patients

OBJETIVO: Descrever o conhecimento atual e as possíveis aplicações de solução hipertônica em pediatria. FONTES DOS DADOS: As referências foram obtidas através do banco de dados Medline, artigos de revisão recentes e através do arquivo pessoal. SíNTESE DOS DADOS: Inicialmente, fizemos uma revisão dos princípios fisiológicos básicos dos fluidos com a distribuição destes nos três compartimentos: intravascular, intersticial e intracelular. Revisamos os achados a respeito dos mecanismos responsáveis pela ação rápida cardiocirculatória, o efeito adicional do componente colóide, descrevemos os termos médicos em relação à ressuscitação de pequenos volumes, as indicações para a sua aplicação, as evidências das pesquisas clínicas (choque hemorrágico, etapa pré-hospitalar do trauma, choque séptico, trauma de crânio), as desvantagens e os efeitos potenciais adversos da ressuscitação com pequenos volumes. CONCLUSÕES: A ressuscitação através de solução salina hipertônica, associada ou não a soluções colóides, envolve um dos conceitos mais inovadores da última década para a ressuscitação primária no paciente com trauma e choque. Atualmente, o espectro de indicações potenciais envolve não apenas a etapa pré-hospitalar no trauma, mas também o período perioperatório e a terapêutica na unidade de cuidados intensivos. Entretanto, tanto para o paciente pediátrico quanto para o paciente adulto, existe a necessidade de pesquisas clínicas randomizadas duplo-cegas adicionais para confirmar as vantagens promissoras em termos de sobrevida.

Amelioration of NaCl stress in Pisum sativum Linn.

Activity of endogenous auxins and growth inhibitors, gibberellins and cytokinins was observed in the extracts of seedlings of Pisum sativum under NaCl stress. After 6 days of germination, when Pisum sativum seedlings were subjected to low concentration of NaCl (50 mM) or boron (10 ppm) increased the endogenous growth regulating substances. Higher concentration of NaCl (150 mM) decreased endogenous level of growth regulators, length of the root and shoot, and fresh and dry weights of seedlings, whereas boron increased the parameters except endogenous growth regulators. Mitotic index and some abnormalities were observed in the treated plants. SDS-PAGE banding pattern of Pisum sativum seedlings extracted in tris-glycine and tris-HCl showed that lower concentration of NaCl increased the number of protein bands, while the higher concentration decreased these protein bands. Combination of boron and NaCl (150 mM) caused an increase in total number of protein bands compared with the total number of bands recorded by using NaCl (150 mM) alone.

Changes in the electrophysiological parameters of the posterior intestine of Anguilla anguilla (Pisces) induced by oxytocin, urotensin II and aldosterone

In view of the importance of the intestine in the osmoregulation of freshwater fishes, we determined the effects of oxytocin, urotensin II (UII), and aldosterone added to the serosal side of the isolated posterior intestine of the freshwater-adapted teleost Anguilla anguilla on electrophysiological parameters. Oxytocin decreased the short-ciruit current (SCC) and transepithelial potential difference (TPD) at a centrations of 1 and 10 mU/ml (to 50 per cent and 42 per cent of control values, respectively), but did not alter these parameters at a concentration of 0.1 mU/ml. UII reduced SCC and TPD at concentrations of 10 nM, 50nM and 100 nM (to 85 per cent of control values), but increased these parameters at the concentration of 500 nM (to 115 per cent of control values). Aldosterone did not alter SCC or TPD at the concentrations tested (10 nM and 100 nM). Oxytocin may open Na+ channels in the apical membrane, allowing the flow of Na+ to the serosa, reduced SCC and TPD. Should this hypothesis be correct, oxytocin would be important for freshwater adaptation, since it would increase absorption. The reduction of SCC and TPD in the posterior intestine A. anguilla induced by UII is evidence that this neurohormone is also important for freshwater adaptation in teleosts. Aldosterone did not show this effect probaly due to the lack of receptors in this organ.

Salmonella typhimurium enterotoxin mediated fluid secretion.

Unidirectional Na+ and Cl- fluxes were studied in rats treated with S. typhimurium enterotoxin (S-LT). There was net absorption of Na+ and Cl- in the control group, while in the toxin treated animals there was net secretion of Na+ and Cl- (P less than 0.001). There was no change in the transport of D-glucose in the toxin treated group as compared to the control animals. The Na+, K(+)-ATPase pump was unaltered in the S-LT treated animals (198.67 +/- 11.23 nmoles Pi/mg protein/min) as compared to the control group (189.93 +/- 10.09 nmoles Pi/mg protein/min). There was no change in the unidirectional fluxes of Ca+2 in the S-LT treated animals as compared to the control animals, suggesting no change in the permeability of the S-LT treated intestinal membrane to Ca+2.

Magnésio mononuclear em hipertensos idosos tratados com tiazídico / Mononuclear magnesium in aged hypertensive patients treated with thiazide

Purpose­To study mononuclear magnesium and serum cations (Na, K and Mg) in elderly hypertensive patients treated with hydrochlorothiazide during 90 days. Patients and Methods­ 15 elderly hypertensive patients treated with hydrochlorothiazide, 25 mg/day or placebo. A method of freezing produced total Iysis of the cells; Mg was measured by atomic spectrophotometry. Results­No differences were noted in mononuclear or serum magnesium in the thiazide or placebo treated patients, and the diuretic produced significant decreases in supine systolic and diastolic blood pressure. Conclusion­Magnesium supplementation does not seem essencial in most patients in this conditions

Recém-nascidos de alto risco: manejo metabólico e hidreletrolítico de manutençäo / Newborns at risk: metabolic mangement and hydroelectrolytic maintenance

O autor, após revisäo da literatura selecionada, propöe critérios e condutas frente ao manejo do metabolismo glico-hidreletrolítico dos recém-nascidos de alto risoc, com objetivo de apoiar a homeostase no período neonatal imediato

Participation of the median raphe nucleus and central serotoninergic pathways in the control of water electrolyte excretion

1. The role of the median raphe nucleus (MRN) and of increased central serotonin (5HT) synthesis/release in the mediation of Na+ excretion (UNaV) and K+ excretion (UKV) and or urine output (UV) was evaluated for 120 min. 2. Male Wistar rats weighing 220-280g were used in each group of 12-13 animals. The rats implanted with a cannula in the MRN were injected with saline (0.5 µl) or with 5.0 and 15.0 ng/0.5 µl kainic acid (KA), an excitatory amino (EAA). Another group of rats was injected ip with 200 mg/Kg saline or tryptophan, the initial precursor of 5HT synthesis. 3. Injection of both kainic acid and tryptophan led to increased Na+ excretion, but the magnitude and time course were different for each treatment. Both KA doses were effective in increasing UNaV (0.061 ñ 0.08, mean ñ SEM, and 0.95 ñ 0.19 -Eq/min, respectively, vs 0.27 ñ 0.04 µEq/min for saline at 60 min). The effect on UKV was statistically significant with the 15.0 ng dose (0.44 ñ 0.05 µEq/min vs 0.25 ñ0.03 µEq/min for saline) at 20 min. 5. Tryptophan adminsitration caused an initial gradual increase in UNaV which became steady and significant after 60 min (1.02 ñ 0.15 µEq/min vs 0.36 ñ 0.06 µEq/min for saline), as well as an increase in UKV (0.58 ñ 0.06 µEq/min vs 0.26 ñ 0.04 µEq/min for saline) at 60 min and throught the remainder of the observation period. 6. KA-induced MRN stimulation and systemic tryptophan overload significantly increased UV at 60, 80 and 100 min (30 to 97% above control values). 7. These data show that kanic acid-mediated transmission at the MRN lellvel may play a modulatory role in hydromineral metabolism. The effects obtained after increased central availability of tryptophan suggest that the excretory response is associated with an increase in 5HT synthesis/release and with an increase in central transmission. 8. We conclude that the data obtained from CA-induced MRN stimulation and systemic tryptophan overload may possibly reflect an increased 5HT synaptic transmission at sites and efferent mechanisms that remain to be elucidated

Interaction between cholinergic and opiate receptors of the lateral hypothalamus in the control of renal excretion in rats

The present study was carried out to investigate the participation and interaction between cholinergic and opiate receptors of the lateral hypothalamus (LH) in the regulation of Na+, K+ and water excretion. Malew Holtzman rats were implanted with chronic cerebral cannulas into the LH. Urine was collected over a period of 2h after injection of carbachol, FK-33824 + carbachol or naloxone + carbachol into the LH. Carbachol (8nmol) reduced urinary volume and increased Na + excretion. Previous injection of FK-333824(100ng) into the LH increased the antidiuretic effect of carbachol, but blocked the increase in Na+ excretion and decreased K+ excretion. Naloxone. Naloxone (10microng) produced no changes in the effect of carbacho9l on renal excretion. These data show an inhibitory effect of opiate receptors on the changes in urinary Na+ and K+ excretion that are induced by chronergic stimulation of the LH in rats, and a potentiating effect on antidiuresis

Participation of the serotonergic system in the regulation of water and electrolyte balance

To determine the possible participation of the serotonergic (5-Ht system in the regulation of water and electrolyte balance, rats were submitted to two sessions of water overloading and the 5-HT agonist MK 212 was administered intracerebroventricularly (icv) in 1.0 micronl 20 min after the second session. Urine volume and sodium and potassium excretion were measured over a priod of 120 min. Microinjection of MK-212 (1 microng/animal) caused a significant reduction (24 to 57%; mean, 43%) in natriuresis throghout the experimental period, and the administration of 10 microng/animal caused a 26-41% reduction (mean, 33%) in kaliuresis. At 20 microng/ animal, MK-212 did not change any of the parameters investigated. No significant change in urine volume was detected after any of the reatments used