Factores asociados a glucemia alterada en ayunas en mujeres adultas no diabéticas / Glycaemic profile and its association with related factors insulin resistance in adult women without diabetes

RESUMEN Introducción: La identificación e intervención de los estados metabólicos previos a la diabetes mellitus tipo 2 (DM 2), permite evitar la aparición de la enfermedad en un alto porcentaje de los casos. Objetivo: Evaluar los factores de riesgo asociados a los valores de glucemia alterada en ayunas (GAA) en mujeres adultas no diabéticas, concurrentes a consulta nutricional en Centro Endocrinológico de la Ciudad Autónoma de Buenos Aires (CABA), Argentina. Materiales y métodos: Estudio transversal y analítico en muestra no probabilística de 316 mujeres (40 a 65 años) no diabéticas, clasificadas según la glucemia en ayunas en dos grupos (Gl <100 mg/dl y Gl ≥100 y <126 mg/dl). Se estudiaron como factores de riesgo relacionados a la GAA: circunferencia de cintura aumentada (CC) >88 cm, peso no saludable según Índice de Masa Corporal (IMC) ≥27 kg/m2, sedentarismo (menos de 150 minutos por semana de actividad física programada), hipertensión arterial (HTA: ≥140/90 mmHg) y relación TG/HDL-C elevada (≥3). Se utilizó el programa estadístico SPSS 19.0 calculando media, desvío estándar y test de Chi cuadrado. El nivel de significación estadístico se fijó en p <0,05. Resultados: La edad media fue 53,6 (DS = 6,5) años, siendo el 35,8% premenopáusicas y 64,2% postmenopáusicas. El 33,2% de la muestra presentó GAA. El 52,8% presentó peso no saludable y el 45,3% CC aumentada. El 66,5% fue sedentaria, el 21,5% HTA y el 22,2% relación TG/HDL-C elevada. La GAA se asoció significativamente con HTA (p <0,001) y relación TG/HDL-C elevada (p <0,001). Conclusiones: Los valores de HTA y la relación TG/HDL-C elevada fueron los dos factores que se asociaron con la GAA en esta muestra. Se recomienda su pesquisa como marcadores tempranos para prevenir el riesgo de DM2.

ABSTRACT Introduction: The identification and intervention of the metabolic states prior to the diabetes mellitus type 2 (DM2), allows to avoid the appearance of the disease in a high percentage of the cases. Objective: To determine the risk factors associated with the values of fasting altered glycemia (GAA) in non-diabetic adult women, concurrent to nutritional consultation at the Endocrinological Center of the Autonomous City of Buenos Aires (CABA), Argentina. Materials and methods: Cross-sectional and analytical study in a non-probabilistic sample of 316 women (40 to 65 years) without diabetes and not pregnant, who were classified according to fasting glycemia in two Groups (Gl <100 mg/dl and Gl≥100 and <126 mg/dl). They were studied as risk factors related to GAA: increased waist circumference (WC) >88 cm, unhealthy body mass index (BMI) ≥27 kg/m2, physical inactivity (less than 150 minutes a week), arterial hypertension (HT: ≥140/90 mmHg) and elevated TG/HDL-C ratio (≥3). The statistical program SPSS 19.0 was used to calculate mean, standard deviation and Chi square test. The level of statistical significance was set at p <0.05. Results: The mean age was 53.6 (SD = 6.5) years (35.8% premenopausal and 64.2% postmenopausal). 33.2% of the sample had GAA. 52.8% had unhealthy weight and 45.3% had increased BCA. 66.5% were sedentary, 21.5% had a diagnosis of hypertension and 22.2% had a high TG/HDL-C ratio. GAA was significantly associated with HTA (p<0,001) and elevated TG / HDL-C ratio (p <0,001). Conclusions: The HTA values and the elevated TG/HDL-C ratio were the two factors that in this study were associated with GAA in this sample. Their research is recommended as early markers to prevent the risk of DM2.

Influyen los valores de tirotrofina sobre el descenso de peso corporal en mujeres adultas con sobrepeso y obesidad? / Do thyrotropin values influence on the decrease of body weight in adult women with overweight and obesity

Introducción: . Objetivos: Estudiar si los valores de TSH influyen sobre el descenso del peso corporal en mujeres adultas con sobrepeso u obesidad. Metodología: Diseño de intervención sobre muestra no probabilística de mujeres >30 años y con IMC ≥25 Kg/m2, que asistieron a un Centro Endocrinológico de la Ciudad Autónoma de Buenos Aires. Resultados: Se estudiaron 105 mujeres (50.8±12.2 años) con un IMC medio de 30.0±4.9 Kg/m2. El 57.1% eran hipotiroideas bajo tratamiento con LT4. Según valor de TSH: Grupo A (27.6%) ≥2.5 mUI/L y Grupo B (72.4%) <2.5 mUI/L. A partir del programa de intervención, la mayoría descendió menos del 1% semanal con respecto a su peso inicial (51.7% grupo A y 56.6% Grupo B), con un grado de adherencia al tratamiento entre el 60 y 70% (51.7% grupo A y 50.1% Grupo B) sin observarse diferencias significativas entre los grupos. No se encontró asociación entre la pérdida de peso semanal con la función tiroidea (OR:0.64; IC:0.29-1.39; p:0.32) ni con valor de TSH (OR:1.21; IC:0.51-2.86; p:0.66). Se encontró correlación directa entre la pérdida de peso semanal y el grado de adherencia al tratamiento (r:0.464; p: 0.000) e inversa con el tiempo transcurrido hasta el primer control (r:-0.30; p: 0.002) y rangos del IMC (r: -0.282; p: 0.004), independientemente de la edad, la función tiroidea o el valor de TSH que presentaban las pacientes. Conclusiones: Los valores de TSH y la función tiroidea no influyeron sobre la pérdida de peso semanal. El descenso de peso se relacionó con la adherencia al tratamiento en forma directa independientemente de la edad, la función tiroidea o el valor de TSH.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

Evaluation of surface water quality using an ecotoxicological approach: a case study of the Piracicaba River (São Paulo, Brazil).

A long-term study was conducted to evaluate Piracicaba River water (São Paulo state, Brazil) using different methodologies and organisms. During 1 year (February 2011 to January 2012), water samples were collected monthly at six different locations and exposed under laboratory conditions to the microcrustaceans Ceriodaphnia dubia and Ceriodaphnia silvestrii for 7 days and to the fish Danio rerio for 4 days to evaluate effects on reproduction and on gill morphology, respectively. Physical-chemical parameters of the water were also measured. Physical-chemical characteristics demonstrated decreasing water quality from upstream to downstream of the river. Effects on the reproduction of C. dubia and C. silvestrii were observed in 3 months (February and March 2011 and January 2012) and occurred in samples collected close to industrialized cities like Americana and Piracicaba. Evaluation of the gills showed normal function of the organ during all months, except in February, September, and October for some locations.

Analysis of pre- and postsynaptic activity in the frog semicircular canal following ototoxic insult: differential recovery of background and evoked afferent activity.

Frogs were treated with a single dose of gentamicin administered intraotically to produce severe degeneration of posterior semicircular canal hair cells and to evaluate the time course of functional damage and recovery both at pre- and postsynaptic level. In isolated canal preparations the endoampullar potential, which reflects the summed receptor potentials of crista hair cells, was progressively reduced in amplitude and completely abolished 6 days after gentamicin treatment. At this time the crista epithelium was devoid of hair cells. The recovery of the endoampullar potential began around 9 days after the ototoxic insult and its amplitude progressively increased to reach, after 20 days, values close to those observed in control experiments. The endoampullar potential amplitude was related to the degree of hair cell regeneration in the crista epithelium. Consistent with the presynaptic damage, the slow generator potential (representing the summed miniature excitatory postsynaptic potential [mEPSP] activity of all posterior nerve fibres) and the resting and evoked spike discharge recorded from the whole ampullar nerve were abolished 6 days after gentamicin treatment. The recovery of the background and evoked afferent activity showed different behaviours. Background spike activity became detectable around 8 days after the ototoxic insult, but was not modulated by canal stimulation at this time, and no generator potential was detected. Moreover, the resting spike frequency fully recovered and reached control values around 15 days after gentamicin treatment, whereas the evoked activity attained normal values only 20 days after the ototoxic insult. These results were confirmed by intracellular recordings from single afferent fibres of the ampullar nerve in intact labyrinth preparations. Absence of any resting and evoked discharge was the most common pattern observed in the early period from 7 to 8 days after gentamicin treatment. Fifty-five percent of impaled afferents were silent while the others showed low resting frequencies of mEPSPs and spikes, and were unresponsive to canal rotation. In the intermediate period from 14 to 15 days after gentamicin treatment, background mEPSP and spike frequencies approached those evaluated in control experiments, but the frequencies of the evoked mEPSPs and spikes were clearly lower than in controls. In the late period, from 18 to 20 days after the ototoxic insult, the impaled afferents showed normal evoked mEPSP and spike frequencies. The present data indicate that the frog semicircular canal completely recovers its pre- and postsynaptic activity following severe ototoxic insult. During the regeneration process, the cytoneural junction regains function and the resting discharge reappears before recovery of mechanoelectrical transduction.

Anatomical patterns of patent foramen ovale (PFO): do they matter for percutaneous closure?

AIM: The aim of this study was to describe and classify the various anatomical pattern of patent foramen ovale (PFO) with transesophageal echocardiography (TEE) and to relate such classification to the selection of PFO closure devices. METHODS: This study enrolled 216 PFO patients (118 females) mostly with previous cryptogenic stroke or transitory ischemic attack (TIA) who underwent percutaneous closure of PFO with deep sedation under TEE control. Anatomical patterns were classified as follows: simple: PFO characterised by central/superior eccentric shunt or with a valve mechanism (45%); reduse: widely redundant septum primum (22%); ASA: atrial septal aneurysm (11%); EASA: entire atrial septal aneurysm (1.4%); CRIB: cribriform septum primum (9%); tunnel: tunnel between septum primum and secundum >10 mm (11%). Degree of right-to-left shunt, either at basal condition or at Valsalva manoeuvre, was classified as: 1=mild (45%); 2=moderate (42%); 3=severe (13%). Additional right-atrium anatomical features are also described. RESULTS: Procedure was successful in 100% of the cases. At follow-up recurrent TIA occurred in two patients. Residual shunts were present in 4.9% of the patients after Valsalva manoeuvre. Palpitations were reported in 4%. CONCLUSIONS: Closing the PFO choosing the device following strict anatomical criteria based on TEE assessment allowed excellent immediate and late results minimizing residual shunts.

The nicotinic activation of the denervated sympathetic neuron of the rat.

Nicotinic responses to endogenous acetylcholine and to exogenously applied agonists have been studied in the intact or denervated rat sympathetic neuron in vitro, by using the two-microelectrode voltage-clamp technique. Preganglionic denervation resulted in progressive decrease of the synaptic current (excitatory postsynaptic current, EPSC) amplitude, which disappeared within 24 h. These effects were accompanied by changes in ion selectivity of the nicotinic channel (nAChR). The extrapolated EPSC null potential (equilibrium potential for acetylcholine action, E(Syn)) shifted from a mean value of -15.9+/-0.7 mV, in control, to -7.4+/-1.6 mV, in denervated neurons, indicating a decrease of the permeability ratio for the main components of the synaptic current (P(K)/P(Na)) from 1.56 to 1.07. The overall properties of AChRs were investigated by applying dimethylphenylpiperazinium or cytisine and by examining the effects of endogenous ACh, diffusing within the ganglion after preganglionic tetanization in the presence of neostigmine. The null potentials of these macrocurrents (equilibrium potential for dimethylphenylpiperazinium action, E(DMPP); and equilibrium potential for diffusing acetylcholine, E(ACh), respectively) were evaluated by applying voltage ramps and from current-voltage plots. In normal neurons, E(Syn) (-15.9+/-0.7 mV) was significantly different from E(DMPP) (-26.1+/-1.0) and E(ACh) (-31.1+/-3.3); following denervation, nerve-evoked currents displayed marked shifts in their null potentials (E(Syn)=-7.4+/-1.6 mV), whereas the amplitude and null potential of the agonist-evoked macrocurrents were unaffected by denervation and its duration (E(DMPP)=-26.6+/-1.2 mV). It is suggested that two populations of nicotinic receptors, synaptic and extrasynaptic, are present on the neuron surface, and that only the synaptic type displays sensitivity to denervation.

DES implantation in saphenous vein and left internal mammary grafts.

Forty percent of patients treated with CABG need further revascularizations after 10 years mainly due to saphenous--more than arterial--graft disease. In this issue, the Authors make a critical review of current available literature on the treatment of saphenous and arterial graft disease, a subset of lesions for which a clear consensus for DES use is still lacking. The Authors examine both the positive and negative aspects of DES use in this setting. Percutaneous revascularizations with DES are feasible and safe. The antiproliferative properties of DES seem to be effective even in the treatment of bypass disease, in particular in saphenous grafts. The clinical efficacy of a treatment with DES is expressed mainly in the reduction of in-stent restenosis and, therefore, in the rates of target lesion revascularization (TLR). Moreover, the use of DES is not associated to higher rates of stent thrombosis and, in case of reintervention, recurrence rates seem to be limited. However, the benefit provided by DES in prevention of restenosis may be limited by the progression of the disease in other segments than those treated with stents. Percutaneous treatment of arterial bypass with DES is feasible and safe. Most of available data on DES are on anastomotic disease (data on bypass ostium and shaft are too scarce to draw any conclusion). In this case, where the use of stents is imperative, there is no evidence of advantages gained by the use of DES over BMS in terms of new revascularizations. Some unanswered questions on DES use in this setting still remain. For this reason new randomized trials are required to definitively give a reliable answer on DES efficacy in this subset of lesions.

Endovascular intervention in the treatment of congenital heart disease in adults.

Over the last years, endovascular intervention have become an important part of treatment in patients with congenital heart disease particularly for residual defects after surgery done in infancy. These transcatheter procedures can be described as dilatation of stenotic sites (angioplasty, endovascular stenting and valvuloplasty) or as a closure of anomalous openings (device closure defects and vascular embolisation). Balloon valvuloplasty, without or with stent, is the procedure of choice in adults with pulmonary valve stenosis, pulmonary arteries stenosis, bicuspid aortic valve stenosis without calcification, aortic re-coarctation. Treatment of native aortic coarctation is still under debate. Devices for closing atrial and ventricular septal defects or patent ductus arteriosus have been developed and are now widely used. Transcatheter, plug or coil occlusion is nowadays the goal treatment in a wide range of arterial and venous vascular connections. This review describes the current role of each major catheter-directed therapy in the treatment of congenital heart disease in adults.

Drug-eluting stents: towards new endpoints.

Drug-eluting stents (DES) have significantly reduced the rates of in-stent restenosis (ISR). As previously observed with bare-metal stents (BMS), either patient's clinical characteristics and lesion morphology may influence the risk of recurrence even with DES. In this review we will focus on the most recent available data on clinical settings where DES efficacy on long-term outcomes are largely unknown. In particular, we report on very complex lesions (bifurcations, small vessels, chronic total occlusions, in-stent restenosis) myocardial infarction, multivessel disease, treatment of bypass graft and of unprotected left main disease. Several issues are still open on DES routinary use for these indications, mainly as far as stent thrombosis is concerned. Recent pathological studies show that DES are characterized by chronic inflammatory infiltrates and delayed endothelialization. Therefore, this effect could translate in a ''vulnerable period'' for thromboses longer than with BMS. Even though large meta-analysis have excluded higher rates of stent thrombosis with DES rather than with BMS, few cases of unusual very late stent thrombosis have been described, pointing out that this problem seems to be still unsolved. Although DES provide better angiographic outcomes in each clinical setting, further randomized studies are running to assess their safety and efficacy on currently off-label indications.

Clinical utility of IVUS in 2005.

Intravascular ultrasounds (IVUS) allowed an innovative visualization of coronary artery disease. This technique developed first in the research field and, then, it was introduced in clinical practice as a supplement to coronary angiography in diagnosis of the severity of ischemic heart disease. The characteristic tomographic view of coronary plaque supplied by IVUS allowed to overcome the limitations of coronary angiography and to add important supplemental information in understanding the mechanism of action of several interventional devices. In this review we analyze current indications of use of IVUS in clinical practice and the future applications of IVUS-related techniques for the diagnosis of coronary artery disease.

Biophysical properties of the silent and activated rat sympathetic neuron following denervation.

A biophysical description of the denervated rat sympathetic neuron is reported, obtained by the two-electrode voltage-clamp technique in mature intact superior cervical ganglia in vitro. At membrane potential values negative to -50 mV, the normal, quiescent neuron displays voltage-dependent K and Cl conductances; following direct or synaptic stimulation (15Hz for 10 s), the neuron moves to a new resting state characterized by increased amplitude and voltage dependence of Cl conductance. Denervation produces two main effects: 1) resting Cl conductance gradually increases while its voltage-dependence decreases; by 30 days a high-conductance resting state prevails, almost independent of membrane potential in the -50/-110 mV range; 2) the increase in amplitude and voltage-dependence of Cl conductance, produced by direct stimulation in control neurons, is less marked in denervated neurons, and is observed over an increasingly small range of membrane potentials. Thirty days after denervation, the prevailing high-conductance resting state appears virtually insensitive to changes in membrane potential and stimulation. Voltage-dependent potassium currents involved in spike electrogenesis (the delayed compound potassium current and the fast transient potassium current) exhibit an early drastic decrease in peak amplitude in the denervated neuron; the effect is largely reversed after 6 days. Remarkable changes in fast transient potassium current kinetics occur following denervation: the steady-state inactivation curve shifts by up to +15 mV toward positive potential and voltage sensitivity of inactivation removal becomes more steep. A comprehensive mathematical model of the denervated neuron is presented that fits the neuron behavior under current-clamp conditions. It confirms that neuronal excitability is tuned by the conductances (mostly chloride conductance) that control the resting membrane potential level, and by fast transient potassium current. Impairment of the latter reduces both inward threshold charge for firing and spike repolarization rate, and fast transient potassium current failure cancels the voltage dependence of both processes.

Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial nitric oxide synthase.

Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs) and impaired bioavailabilty of nitric oxide (NO) are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5' nuclease assays (TaqMan PCRs) to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA) and 15 with acute coronary syndromes (ACS) without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS) gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001) in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype. The eNOS gene was more expressed in ACS plaques and VSMCs cultured from them, thus indicating that: a) the expression of the most important differentiation markers is retained under in vitro conditions; and b) NO may play a pivotal role in coronary artery disease. Our findings suggest a new cell system model for studying the pathophysiology of unstable angina and myocardial infarction.

Inhibitors of platelets glycoprotein IIb/IIIa (GP IIb/IIIa) receptor: rationale for their use in clinical cardiology.

The glycoprotein IIb/IIIa (GP IIb/IIIa) receptor is the most important receptor involved in platelet aggregation. A stable GP IIb/IIIa inhibition is required when a massive platelet activation triggers thrombosis. Three GP IIb/IIIa inhibitors are currently approved for clinical use: abciximab, tirofiban and integrilin. Their different pharmacodynamic and pharmacokinetic properties reflect a different efficacy in platelet inhibition.

First Report of Clubroot of Eruca sativa Caused by Plasmodiophora brassicae in Brazil.

Eruca sativa Mill. (family Brassicaceae), with its origin in western Asia, is a culinary and pharmacological species cultivated in Europe, Brazil, and other countries. In the United States, it is a minor crop known as arugula or roquette. Clubroot on E. sativa has not been reported in Brazil and has been reported once in the United States in 1914 (1,2,3). On several occasions since 2000, stunted and wilted plants (cv. Rúcula Cultivada) were collected from growers' fields and greenhouses that had been direct-seeded in Vargem Bonita, DF (two fields and one greenhouse) and Quatro Barras, PR (two fields). The infected arugula crops were found in areas where other plants from the genus Brassica were traditionally cultivated. Disease incidence in individual fields varied from 20 to 80%. Diseased plants were severely affected with hypertrophic, malformed roots, and root galls resembling Woronin's description (4). Plasmodia and resting spores in thin sections prepared from root galls were observed with compound and electron microscopes. Pathogenicity tests were conducted on arugula and Brassica pekinensis (Lour.) Rupr. (universal host) with inoculum from naturally infected arugula. The soil of potted test plants at the four-to-five-leaf stage was drenched with a suspension of resting spores. Symptoms identical to those observed on the original plants were produced on all inoculated plants 2 to 3 weeks after inoculation. Control plants remained symptomless. The pathogen was positively identified as Plasmodiophora brassicae Wor. with the combination of macroscopic and microscopic symptoms and signs of the disease and pathogen. P. brassicae was first reported in Brazil in 1965 in the state of São Paulo and in the 1980s in Distrito Federal on several members of the Brassicae. To our knowledge, this is the first report of P. brassicae infecting E. sativa in Brazil. Arugula is a susceptible host and should not be planted on P. brassicae-infested land. References: (1) D. Farr et al. Fungi on Plants and Plant Products in the United States. The American Phytopathological Society, St. Paul, MN. 1989. (2) D. F. Farr et al. Fungal Databases. Systematic Botany and Mycology Laboratory, On-line publication. ARS, USDA, 2003. (3) J. S. Karling. The Plasmodiophorales. Published by J. S. karling, NY. 1942. (4) M. S. Woronin. Plasmodiophora brassicae the Cause of Cabbage Hernia. Phytopathological Classics 4. The American Phytopathological Society, Ithaca, NY, 1934.

Infantile cerebellar thrombosis: a case of lupus anticoagulants?

Lupus Anticoagulants (LA) pathology is a disease frequently associated with venous and/or arterial thrombosis. The authors describe a 6 year-old boy complaining cephalea and emesis, followed by lethargy, in whom antiphospholipids antibodies were detected. Brain magnetic resonance scans showed lesions of the cerebellum. The characteristics of LA disease are discussed.

No evidence for calcium electrogenic exchanger in frog semicircular canal hair cells.

We investigated the possibility that, in hair cells mechanically isolated from frog semicircular canals, Ca2+ extrusion occurs via a Na+ : Ca2+ (cardiac type) or a Na+ : Ca2+,K+ (retinal type) exchanger. Cells concurrently imaged during whole-cell patch-clamp recordings using the Ca2+ sensitive fluorescent dye Oregon Green 488 BAPTA-1 (100 micro m) showed no voltage dependence of Ca2+ clearance dynamics following a Ca2+ load through voltage-gated Ca2+ channels. Reverse exchange was probed in hair cells dialyzed with a Ca2+- and K+-free solution, containing a Na+ concentration that saturates the exchanger, after zeroing the contribution to the whole-cell current from Ca2+ and K+ conductances. In these conditions, no reverse exchange current was detected upon switching from a Ca2+-free external solution to a solution containing concentrations of Ca2+ alone, or Ca2+ + K+ that saturated the exchanger. By contrast, the same experimental protocol elicited peak exchange currents exceeding 100 pA in gecko rod photoreceptors, used as positive controls. In both cell types, we also probed the forward mode of the exchanger by rapidly increasing the intracellular Ca2+ concentration using flash photolysis of two novel caged Ca2+ complexes, calcium 2,2'-([1-(2-nitrophenyl)ethane-1,2-diyl]bis(oxy))bis(acetate) and calcium 2,2'-([1-(4,5-dimethoxy-2-nitrophenyl)ethane-1,2-diyl]bis(oxy)) bis(acetate), in the presence of internal K+ and external Na+. No currents were evoked by UV-triggered Ca2+ jumps in hair cells, whereas exchanger conformational currents up to 400 pA, followed by saturating forward exchange currents up to 40 pA, were recorded in rod photoreceptors subjected to the same experimental conditions. We conclude that no functional electrogenic exchanger is present in this hair cell population, which leaves the abundant plasma membrane Ca2+-ATPases as the primary contributors to Ca2+ extrusion.

Quantitative neuropathological analysis of sudden infant death syndrome.

Detailed stereological analyses of specific regions of brains of children who had died from Sudden Infant Death Syndrome (SIDS) was undertaken to determine whether global evidence of an underlying pathology exists, contributing to an increased susceptibility to SIDS. A significant reduction in the total number of neocortical neurones and neurone volume was observed in SIDS normal birth weight (NBW) infants in comparison to controls. A significant reduction in both volume and total neurone number were also noted in the dorsal motor nucleus of the vagus in SIDS NBW group when compared with controls. Anomalies in regions of the brain involved with cardiorespiratory control (brainstem) and arousal (brainstem and neocortex) may play a crucial role in the chain of events resulting in a SIDS event.