Comparison of platforms for testing antibodies to Chlamydia trachomatis antigens in the Democratic Republic of the Congo and Togo.

Trachoma, caused by repeated ocular infection with Chlamydia trachomatis (Ct), is targeted for elimination as a public health problem. Serological testing for antibodies is promising for surveillance; determining useful thresholds will require collection of serological data from settings with different prevalence of the indicator trachomatous inflammation-follicular (TF). Dried blood spots were collected during trachoma mapping in two districts each of Togo and Democratic Republic of the Congo. Anti-Ct antibodies were detected by multiplex bead assay (MBA) and three different lateral flow assays (LFA) and seroprevalence and seroconversion rate (SCR) were determined. By most tests, the district with > 5% TF (the elimination threshold) had five-sixfold higher seroprevalence and tenfold higher SCR than districts with < 5% TF. The agreement between LFA and MBA was improved using a black latex developing reagent. These data show optimization of antibody tests against Ct to better differentiate districts above or below trachoma elimination thresholds.

Rhabdomyolysis with Acute Renal Failure and Deep Vein Thrombosis Induced by Antipsychotic Drugs: A Case Report.

Atypical antipsychotics, the first line therapy for schizophrenia, have already been reported as causing rhabdomyolysis or isolated elevation in serum creatine kinase (SCK). This case report dealing with rhabdomyolysis in a 25-year-old man treated with antipsychotics is particularly unusual, due to the extremely high elevation in SCK and the ensuing acute renal failure. He was treated with loxapine 400 mg/day and risperidone 4 mg/day for 4 days and then loxapine was replaced by levomepromazine 300 mg/day. A series of laboratory examinations showed: SCK 43 650 UI/L, creatinine 392 µmol/L. An acute renal failure (acute tubular necrosis) after iatrogenic rhabdomyolysis was diagnosed, requiring hemodialysis. Furthermore, the patient also developed a deep vein thrombosis (DVT) attributed to his antipsychotic treatment. This case underlines the importance of taking rhabdomyolysis and DVT risk factors into account in patients treated with antipsychotics. Indeed, in this case we note that rhabdomyolysis was probably promoted by the interruption and the reintroduction of the treatment more than by possible dehydration, because no other risk factor could be identified.

Effects of ACh and adenosine mediated by Kir3.1 and Kir3.4 on ferret ventricular cells.

The inotropic effects of ACh and adenosine on ferret ventricular cells were investigated with the action potential-clamp technique. Under current clamp, both agonists resulted in action potential shortening and a decrease in contraction. Under action potential clamp, both agonists failed to decrease contraction substantially. In the absence of agonist, application of the short action potential waveform (recorded previously in the presence of agonist) also resulted in a decrease in contraction. Under action potential clamp, application of ACh resulted in a Ba(2+)-sensitive outward current with the characteristics of muscarinic K+ current (I(K,ACh)); the presence of the muscarinic K+ channel was confirmed by PCR and immunocytochemistry. In the absence of agonist, on application of the short ACh action potential waveform, the decrease in contraction was accompanied by loss of the inward Na(+)/Ca(2+) exchange current (I(NaCa)). ACh also inhibited the background inward K+ current (I(K,1)). It is concluded that ACh activates I(K,ACh), inhibits I(K,1), and indirectly inhibits I(NaCa); this results in action potential shortening, decrease in contraction, and, as a result of the inhibition of I(K,1), minimum decrease in excitability.

AtZFP1, encoding Arabidopsis thaliana C2H2 zinc-finger protein 1, is expressed downstream of photomorphogenic activation.

C2H2 zinc-finger proteins play important roles in plant development including floral organogenesis, leaf initiation, lateral shoot initiation, gametogenesis and seed development. The gene for one such protein from Arabidopsis, AtZFP1 (Arabidopsis thaliana zinc-finger protein 1), is expressed at high levels in the shoot apex, including the apical meristem, developing leaves and the developing vascular system. In light-grown seedlings, AtZFP1 expression is induced about three days after germination, before the expansion of the true leaves. Dark-grown plants, in which photomorphogenesis is repressed, have no detectable AtZFP1 expression in the shoot apex. Under conditions which induce or mimic photomorphogenic development including growth in the light, shifting dark-grown plants to continuous light or growth on cytokinin in the dark, high levels of AtZFP1 expression are detected. Furthermore, AtZFP1 expression does not depend on active photosynthesis as shown by analysis of plants grown on the carotenoid biosynthetic inhibitor norflurazon. These results are discussed in relation to a possible role for AtZFP1 in shoot development, downstream of photomorphogenic activation.

The role of Na(+)-Ca2+ exchange current in electrical restitution in ferret ventricular cells.

1. The mechanisms underlying electrical restitution (recovery of action potential duration after a preceding beat) were investigated in ferret ventricular cells. The time to 80% recovery (t80) of action potential duration was approximately 204 ms. 2. At a holding potential of -80 mV, the Ca2+ current (ICa) reactivated and the delayed rectifier K+ current (IK) deactivated very rapidly (t80: approximately 32 and approximately 93 ms, respectively). The kinetics of both currents are too fast to account for electrical restitution alone. 3. The putative inward Na(+)-Ca2+ exchange current (INa-Ca) produced by the Na(+)-Ca2+ exchanger in response to the intracellular Ca2+ transient reprimed (t80: 189 ms) with the same time course as mechanical restitution (recovery of contraction) and with a similar time course to electrical restitution. 4. Substantial reduction of inward INa-Ca, by buffering intracellular Ca2+ with the acetyl methyl ester form of BAPTA, shortened the action potential and greatly altered the electrical restitution curve. Subsequent addition of nifedipine (to block ICa) or 4-aminopyridine (4-AP) (to block the transient outward current, ITO) further altered the electrical restitution curve. 5. Any time-dependent current that contributes to the action potential is likely to affect the time course of electrical restitution. Although ICa, IK and ITO were previously thought to be the only currents involved in electrical restitution, we conclude that inward INa-Ca also plays an important role.

The role of inward Na(+)-Ca2+ exchange current in the ferret ventricular action potential.

1. Inward Na(+)-Ca2+ exchange current (iNaCa) was either blocked in ferret ventricular cells by replacing extracellular Na+ with Li+ or substantially reduced by the almost complete elimination of the Ca2+ transient by buffering intracellular Ca2+ with the acetoxymethyl ester form of BAPTA (BAPTA AM). 2. During square wave voltage clamp pulses to 0 mV, replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ with BAPTA AM resulted in the loss of a transient inward current. This current was increased by the application of isoprenaline (expected to increase the underlying Ca2+ transient) and displayed the voltage-dependent characteristics of inward iNaCa. 3. Replacing extracellular Na+ with Li+ or buffering intracellular Ca2+ caused a significant shortening of the action potential (at -65 mV, 44 +/- 2% with Li+ and 20 +/- 2% with BAPTA AM). The shortening can be explained by changes in iNaCa. 4. The action potential clamp technique was used to measure the BAPTA-sensitive current (putative iNaCa) and the Ca2+ current (ica; measured using nifedipine) during the action potential. Under control conditions, the inward BAPTA-sensitive current makes approximately the same contribution as iCa during much of the action potential plateau. These results suggest an important role for inward iNaCa in the ferret ventricular action potential.

The role of Na-Ca exchange current in the cardiac action potential.

Since 1981, when Mullins published his provocative book proposing that the Na-Ca exchanger is electrogenic, it has been shown, first by computer simulation by Noble and later by experiment by various investigators, that inward iNaCa triggered by the Ca2+ transient is responsible for the low plateau of the atrial action potential and contributes to the high plateau of the ventricular action potential. Reduction or complete block of inward iNaCa by buffering intracellular Ca2+ with EGTA or BAPTA, by blocking SR Ca2+ release or by substituting extracellular Na+ with Li+ can result in a shortening of the action potential. The effect of block of outward iNaCa or complete block of both inward and outward iNaCa on the action potential has not been investigated experimentally, because of the lack of a suitable blocker, and remains a goal for the future. An increase in the intracellular Na+ concentration (after the application of cardiac glycoside or an increase in heart rate) or an increase in extracellular Ca2+ are believed to lead to an outward shift in iNaCa at plateau potentials and a shortening of the action potential. Changes in the Ca2+ transient are expected to result in changes in inward iNaCa and thus the action potential. This may explain the shortening of the premature action potential as well as the prolongation of the action potential when a muscle is allowed to shorten during the action potential. Inward iNaCa may play an important role in both normal and abnormal pacemaker activity in the heart.

Regional differences in the negative inotropic effect of acetylcholine within the canine ventricle.

1. Regional differences in the effects of ACh on sub-epicardial, mid-wall and sub-endocardial cells of the dog left ventricle have been studied. 2. ACh produced a dose-dependent, atropine-sensitive negative inotropic effect that was greatest in sub-epicardial cells and small or absent in sub-endocardial cells. 3. In sub-epicardial (but not sub-endocardial) cells, ACh also resulted in a dose-dependent decrease in action potential duration. The inotropic effect of ACh on sub-epicardial cells was primarily the result of the decrease of action potential duration, because during trains of voltage clamp pulses the inotropic effect of ACh was reduced or abolished. At a holding potential of -80 mV, 10(-5)M ACh decreased L-type Ca2+ current by approximately 8% and this is thought to be responsible for the small inotropic effect during trains of pulses. 4. Although 4-AP, a blocker of the transient outward current (I(to)), abolished the "spike and dome' morphology of the sub-epicardial action potential, it had little or no effect on the actions of ACh on sub-epicardial cells. ACh had no effect on I(to) in sub-epicardial cells in voltage clamp experiments. 5. ACh activated a Ba(2+)-sensitive outward current (IK,ACh) in sub-epicardial cells, but little or no such current in sub-endocardial cells. In sub-epicardial cells, ACh also inhibited the inward rectifier current, IK,1. 6. It is concluded that in left ventricular sub-epicardial cells, ACh activates IK,ACh. This results in a shortening of the action potential and, therefore, a negative inotropic effect. In subendocardial cells, ACh activates little or no IK,ACh and, therefore, it has little or no negative inotropic effect. This may result from a regional variation in the expression of the muscarinic K+ channel.