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Biomedical subjects

M Zaidi

Publications and source records attributed to M Zaidi.

At least 19 recordsLinked to original sources
PubMed1997

Dispersion of ventricular repolarization in dilated cardiomyopathy.

OBJECTIVE: Increased dispersion of ventricular repolarization has been shown to be a marker for increased risk of ventricular tachyarrhythmias in various cardiac disorders. The present study is aimed at comparing the values of four dispersion indices in four clinical groups: normal subjects (n = 23), patients with intraventricular conduction defects (QRS > 0.12 s) without underlying cardiac disease (n = 30), patients with dilated cardiomyopathy (n = 36), and patients with both dilated cardiomyopathy and ventricular conduction defects (n = 18). METHODS: On an averaged cycle from a 10 s record of 15 simultaneous leads (12-lead ECG and XYZ leads), and after interactive editing, four intervals were computed: JTapex, JTend, QTapex and QTend. For each interval, the dispersion is defined as the difference between the maximal and minimal values across the 15 leads. RESULTS: The mean values of all four dispersion indices were significantly smaller in the normal group than in the three other groups (P < 0.001). Among patients with dilated cardiomyopathy, those with intraventricular conduction defects had significantly higher dispersion values than those without, even disregarding the QRS duration (P < 0.01). Thus, patients with both dilated cardiomyopathy and ventricular conduction defects have larger dispersion values than patients with ventricular conduction defects alone (P < 0.01) and than those with dilated cardiomyopathy without intraventricular conduction defects. CONCLUSION: Dispersion of ventricular repolarization is increased in patients with dilated cardiomyopathy, especially in those with ventricular conduction defects, suggesting that they are at higher risk of arrhythmic events.

Adult↗
PubMed1996

Dispersion of ventricular repolarization in hypertrophic cardiomyopathy.

On an averaged QRS-T cycle from a 15-lead record (12-lead electrocardiogram + XYZ leads) and through interactive editing, four electrocardiographic indices of the dispersion of ventricular repolarization (DVR) are automatically computed and represent the maximal interlead difference of QT and JTend and QT and JTapex. The values of these indices were then examined in three clinical groups matched for age and sex: normal subjects (control), patients with left ventricular hypertrophy (LVH group), and patients with hypertrophic cardiomyopathy (HCM group) without ventricular arrhythmias and without interacting drugs. The mean values of all four DVR indices were significantly increased in the HCM group compared with the control group and the LVH group of another origin (ie, for the QTe dispersion index, the mean values and the 97.5th percentiles were, respectively, 65 +/- 18 ms and 97 ms in the HCM group, 41 +/- 25 ms and 79 ms in the LVH group, and 31 +/- 15 ms and 58 ms in the control group). The maximal QT interval was also significantly longer in the HCM group (464 +/- 30 ms) than in the LVH group (436 +/- 32 ms) and the control group (428 +/- 25 ms).

Adult↗
PubMed1996

Computer-assisted study of ECG indices of the dispersion of ventricular repolarization.

A new computer-assisted method for the quantitative assessment of the dispersion of ventricular repolarization (DVR) has been developed. Through interactive editing of an averaged QRS-T cycle from a 15-lead electrocardiographic (ECG) record (12-lead ECG + XYZ leads), five ECG indices of DVR are automatically computed: they represent the maximal interlead difference of QT and the intervals from the J point to the T wave end, from the J point to the T wave apex, and from the T wave apex to the T wave end. The standard limits of these indices were then established in six clinical groups, including normal subjects and patients with left ventricular hypertrophy, with myocardial infarction, and with intraventricular conduction defect, all subjects being without ventricular arrhythmias and without interacting drugs. The mean values and percentile ranges of all DVR indices were lower in the normal group than in all pathologic groups. The 97.5th percentiles of the QT end dispersion and the JT end dispersion were, respectively, 65 and 76 ms in normal subjects, 84 and 86 ms in patients with inferior MI; 89 and 100 ms in those with anterior MI; 90 and 98 ms in those with left ventricular hypertrophy; and 94 and 99 ms in those with intraventricular conduction defects. This suggests that increased DVR is associated with the varieties of heart disease represented in this study, even in the absence of ventricular arrhythmias, and also that individual measurements of DVR used as predictors of future arrhythmic events should be referred to the standard range of their own clinical group.

Adult↗
PubMed1996

Extracellularly applied ruthenium red and cADP ribose elevate cytosolic Ca2+ in isolated rat osteoclasts.

We demonstrated recently that the divalent cation-sensing receptor on the osteoclast, the Ca2+ receptor (CaR), is a functional component of a cell surface-expressed ryanodine receptor-like molecule (RyR). The objective of the present study was to further characterize this putative RyR by use of the two well-known cell-impermeant RyR modulators, ruthenium red and adenosine 3',5'-cyclic diphosphate ribose (cADPr). We found that, when applied extracellularly, ruthenium red (5 x 10(-8)-10(-4) M) and cADPr (5 x 10(-6) M) triggered an elevation of cytosolic [Ca2+]. Depolarization of the cell membrane by the application of 0.1 M K+ in the presence of 5 x 10(-6) M. valinomycin resulted in a concentration-dependent increase in the magnitude of the cytosolic Ca2+ response to extracellular ruthenium red (5 x 10(-9) and 5 x 10(-5) M), a phenomenon that was not seen when osteoclasts were hyperpolarized using 5 x 10(-3) M K+ with 5 x 10(-6) M valinomycin. In the presence of an intact nonleaky cell membrane, these results would favor a plasma membrane locus of action for the two modulators. Furthermore, pretreatment of osteoclasts with either modulator resulted in a markedly attenuated cytosolic Ca2+ transient elicited in response to the CaR agonist Ni2+, thus confirming an interaction between the cADPr- and ruthenium red-sensitive sites and the osteoclast CaR. The inhibition of the cytosolic Ca2+ response to Ni2+ induced by ruthenium red remained unchanged in the face of membrane potential changes. Finally, the cytosolic Ca2+ response to caffeine (5 x 10(-4) M), another RyR modulator, was also strongly attenuated by pretreatment with 5 x 10(-9) M ruthenium red. We conclude that ruthenium red and cADPr act on plasma membrane-resident sites and that both these sites interact with the process of divalent cation sensing.

Adenosine Diphosphate Ribose↗
PubMed1996

Regulation of extracellular calcium sensing in rat osteoclasts by femtomolar calcitonin concentrations.

Certain eukaryotic cells can sense changes in their extracellular Ca2+ concentration through molecular structures termed Ca(2+)-sensing receptors (CaRs). We have shown recently that in the bone-resorbing osteoclast, a unique cell surface-expressed ryanodine receptor (RyR), functions as the CaR. The present study demonstrates that the sensitivity of this receptor is modulated by physiological femtomolar concentrations of the bone-conserving hormone, calcitonin. Calcitonin was found to inhibit cytosolic Ca2+ responses to both Ca2+ and Ni2+. The latter inhibition was mimicked by amylin (10(-12) M), calcitonin gene-related peptide (10(-12) M), cholera toxin (5 micrograms/l) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (2.5 x 10(-4) or 5 x 10(-4) M) and was reversed by the protein kinase A phosphorylation inhibitor, IP-20. Finally, using a quench flow module, we showed that cellular cAMP levels rise to a peak within 25 ms of calcitonin application; this is consistent with the peptide's rapid effect on CaR activation. We conclude, therefore, that cAMP plays a critical role in the control of CaR function by calcitonin.

Animals↗
PubMed1995

Extracellular cation sensing by the enterocyte: prediction of a novel divalent cation "receptor".

We report that the divalent cation Ni2+ elicits elevations in the cytosolic free Ca2+ concentration ([Ca2+]) in cultured enterocytes. These elevations were monophasic, each response consisting of a rapid initial transient rise of cytosolic [Ca2+] to a peak value followed by an exponential decline. The magnitude of the cytosolic [Ca2+] elevation varied with the concentration of applied Ni2+. In some cells, a single application of Ni2+ induced oscillatory changes in cytosolic [Ca2+]. There was also evidence for use-dependent inactivation: a conditioning application of Ni2+ substantially attenuated the response resulting from its subsequent application. Our findings thus demonstrate the existence of a divalent cation-sensing "receptor" on the enterocyte. This putative receptor may play a role in regulating mineral absorption across the enterocyte membrane.

Calcium↗
PubMed1995

Effect of membrane potential on surface Ca2+ receptor activation in rat osteoclasts.

Osteoclasts are known to possess a divalent cation-sensitive receptor, the Ca2+ receptor (CaR). The latter monitors changes in the local Ca2+ concentration generated as a result of hydroxyapatite dissolution. CaR activation elevates cytosolic [Ca2+] and thereby inhibits osteoclastic bone resorption. Recent studies have used Ni2+ as a surrogate CaR agonist to elicit changes in cytosolic [Ca2+]. This article examines the effects of membrane potential changes on the kinetics of the cytosolic [Ca2+] signal resulting from such Ni(2+)-induced CaR activation. Membrane potential was altered through variations in the extracellular [K] in combination with applications of the K+ ionophore, valinomycin. Membrane potential changes were confirmed by independent electrophysiological patch clamp studies of whole osteoclasts. The application of valinomycin produced a distinct, sustained elevation of cytosolic [Ca2+] in single fura 2-loaded cells, a "primary" response. This response was independent of valinomycin concentration (between 5 nM to 5 microM) and persisted in Ca(2+)-free, EGTA-containing solutions. It also persisted both in high (105 mM) and low (5 mM) extracellular [K+]. A gradual "secondary" elevation of cytosolic [Ca2+] then followed with the continued application of valinomycin, but this was eliminated by sequestering the extracellular [Ca2+] or by increasing extracellular [K+] from 5 to 105 mM. In a separate set of experiments, the presence of 5 microM [valinomycin]-([K+] = 5 mM) prolonged the cytosolic [Ca2+] signal elicited by 50 microM-[Ni2+] application. These prolonged kinetics persisted in low extracellular [Ca2+] (zero-added Ca2+), but reverted to a rapid time-course in the presence of 105 mM-[K+] or at higher [Ni2+] (500 microM and 5 mM). The experiments thus indicate that membrane voltage modifies the kinetics of CaR activation by Ni2+ and therefore suggests that the CaR is an integral protein in the osteoclast surface membrane.

Animals↗
PubMed1995

Disinfection and sterilization practices in Mexico.

We evaluated antisepsis, disinfection, and sterilization procedures at 22 hospitals in the state of Yucatan, Mexico, which provide services for approximately 80% of the population. The percentage of hospitals that followed standard recommendations for diverse antisepsis procedures were as follows: surgical scrub, 41%; surgical site preparation, 68%; central intravenous (iv) catheters, 61%; peripheral iv catheters, 86%; urinary catheters, 41%, and umbilical cord care, 5%. Inappropriate procedures typically involved the use of benzalkonium chloride and mercury compounds. Adequate sterilization procedures were observed for sharp surgical instruments in 9%, for blunt surgical instruments in 81%; for linen in 90%; for surgical brushes in 9%; for metal prostheses in 100%; for plastic prostheses in 57%; and for disinfection of endoscopes in 30%. The most common errors were the use of too short an exposure time in steam sterilizers or dry heat sterilizers, and the use of benzalkonium chloride as a sterilizing agent. Only 14% of hospitals used commercial spore preparations for autoclave monitoring. For the reuse of disposables, 50-94% of hospitals employed inappropriate sterilization or low-level disinfection procedures. Similar conditions are likely to exist in hospitals throughout the country. The establishment of strict regulations and hospital training programmes for disinfection and sterilization procedures, and the reuse of disposable devices is urgently needed in Mexico.

Cross Infection↗
PubMed1995

Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release.

A ryanodine-sensitive pathway is involved in intracellular Ca2+ release in response to activation of the osteoclast cell surface Ca2+ receptor. We now report that the ryanodine-receptor modulator, caffeine itself released intracellularly stored Ca2+ and, strongly inhibited Ca2+ release triggered in response to Ca(2+)-receptor activation by Ni2+, a surrogate cation agonist. Caffeine yielded a bell-shaped concentration-response curve (0.005-2 mM) and displayed use-dependent inactivation. Furthermore, responses to caffeine were abolished on prior application of Ni2+ (5 mM). Subthreshold (0.005 mM) caffeine concentrations abolished Ni(2+)-induced elevations in the cytosolic Ca2+ concentration ([Ca2+]). However, in a Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing solution (extracellular [Ca2+] < 10 nM), caffeine (0.5 mM) neither elevated [Ca2+] nor inhibited the response to Ni2+. Finally, when caffeine was applied to intercept the plateau phase of the cytosolic Ca2+ signal triggered by extracellular Ca2+ elevation (10 mM), a rapid but reversible inactivation followed. These studies strongly indicate the existence of a caffeine-sensitive mechanism for the release of intracellularly stored Ca2+ in the osteoclast.

Animals↗
PubMed1995

A ryanodine receptor-like molecule expressed in the osteoclast plasma membrane functions in extracellular Ca2+ sensing.

Ryanodine receptors (RyRs) reside in microsomal membranes where they gate Ca2+ release in response to changes in the cytosolic Ca2+ concentration. In the osteoclast, a divalent cation sensor, the Ca2+ receptor (CaR), located within the cell's plasma membrane, monitors changes in the extracellular Ca2+ concentration. Here we show that a RyR-like molecule is a functional component of this receptor. We have demonstrated that [3H] ryanodine specifically binds to freshly isolated rat osteoclasts. The binding was displaced by ryanodine itself, the CaR agonist Ni2+ and the RyR antagonist ruthenium red. The latter also inhibited cytosolic Ca2+ elevations induced by Ni2+. In contrast, the responses to Ni2+ were strongly potentiated by an antiserum Ab129 raised to an epitope located within the channel-forming domain of the type II RyR. The antiserum also stained the surface of intact, unfixed, trypan blue-negative osteoclasts. Serial confocal sections and immunogold scanning electron microscopy confirmed a plasma membrane localization of this staining. Antiserum Ab34 directed to a putatively intracellular RyR epitope expectedly did not stain live osteoclasts nor did it potentiate CaR activation. It did, however, stain fixed, permeabilized cells in a distinctive cytoplasmic pattern. We conclude that an RyR-like molecule resides within the osteoclast plasma membrane and plays in important role in extracellular Ca2+ sensing.

Animals↗
PubMed1994

Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible linkage between Ca2+ sensing and extracellular acidification.

We report a sensitivity of the osteoclast cell surface Ca2+ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+ receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca2+ release.

Animals↗
PubMed1994

Elevated cytosolic calcium levels in human lymphocytes during surface virus infections.

Generalised metabolic and electrolyte disturbances are known to accompany both plasma and surface virus infections. We have investigated whether these infections could impair the transport of Ca2+ from cells under conditions of controlled concentrations of the energy substrate glucose. Thus, cytosolic calcium levels ([Ca2+]i) were measured in single isolated lymphocytes obtained from healthy volunteers or those suffering from coryza. Before making measurements using a Ca(2+)-sensitive fluorescent dye indo 1, we incubated lymphocytes in buffers containing 0 mM-, 5.6 mM- or 11.2 mM-[glucose]. We found that [Ca2+]i of lymphocytes obtained from the sick were significantly higher than those from healthy controls both at 0 mM and 5.6 mM-[glucose], and that [Ca2+]i was inversely related to the media glucose concentration for both groups. These results suggest a diminished capacity of cation pumping in viral infections, such as coryza, in relationship to the available glucose as energy substrate.

Calcium↗
PubMed1994

Effect of raised extracellular calcium on cell spread area in quail medullary bone osteoclasts.

The present study reports on the effects of extracellular calcium ([Ca2+]o) elevation and ionomycin on cell spread area of medullary bone osteoclasts freshly isolated from egg-laying Japanese quail. The responses were compared with those demonstrated in osteoclasts cultured for periods of 5-8 days and also to those previously demonstrated in neonatal rat osteoclasts. Freshly isolated medullary bone osteoclasts, unlike rat osteoclasts, were refractory to 20 mM [Ca2+]o, in that they showed no change in cell spread area. They did, however, show a modest (15%) reduction in cell spread area to ionomycin (7-50 microM), applied for 15-30 min. When medullary bone osteoclasts were precultured for 5-8 days, they exhibited a well-developed response to 20 mM [Ca2+]o with a 46% reduction in cell spread area. They also showed a similar reduction in cell spread area in response to ionomycin (4 microM). It is concluded that, unlike freshly isolated neonatal rat osteoclasts, those obtained from quail medullary bone appear refractory to inhibitory factors such as [Ca2+]o. However, when the avian cells are cultured for a few days they appear to recover their ability to respond to [Ca2+]o.

Animals↗
PubMed1994

Dimensional analysis of osteoclastic bone resorption and the measurement of biologically active calcitonin.

Calcitonin inhibits bone resorption through a direct action on the osteoclast. We report a quantitative analysis of bone resorption by disaggregated rat osteoclasts. We then used our findings to develop a formal bioassay for calcitonin. Osteoclasts were mechanically disaggregated from neonatal rat long bones and dispersed at low densities on slices of devitalized bovine cortical bone. The resulting areas of bone excavation were quantified to micrometric precision by scanning electron microscopy together with computer-assisted image analysis. These findings were correlated with the volumes of bone resorption in the same slices measured by confocal scanning microscopy for the first time. The total planar areas of bone resorption per slice correlated linearly (r = 0.78) with the confocal microscopic measurements of total volume resorbed, provided that volume was expressed to its two-thirds power. The latter transformation resulted in representations of the determined areas ([length]2) and volumes ([length]3) which were dimensionally consistent. These findings thus demonstrate that osteoclastic bone excavations show a consistent relationship between area and volume and that assessments of the area of excavations accordingly provide an empirical representation of the volume of bone resorbed. Furthermore, in view of the skewed nature of the distributions of area measurements, we assessed the effect of transforming the response variable to derive a metameter, (planar area of resorption)1/2. Such transformed data points, which expressed the data in the dimensions of [length], were more normally distributed than the raw data points and had more stable variances over a wider concentration range. We accordingly determined relative potencies using parallel line analyses on the transformed data. The latter offered a consistent correlation to the volume measurements when these were also converted to dimensions of [length] (r = 0.805). It was confirmed that the inhibition of bone resorption by calcitonins from various species, namely, pig, salmon and eel, was quantitatively dependent upon concentration of the respective peptides. The resulting assay was also found to be sufficiently sensitive to measure picomolar peptide concentrations with a precision, lambda (standard deviation/slope), ranging between 0.3 and 0.8. Finally, we identified factors affecting assay precision and sensitivity.

Animals↗
PubMed1994

Calcium influx and release in isolated rat osteoclasts.

Intracellular and extracellular sources of cytosolic [Ca2+] elevation in isolated rat osteoclasts were explored by a comparison of fura-2 signals in response to application of the Ca2+ ionophore, ionomycin, in Ca(2+)-containing and in Ca(2+)-free bathing solutions. Cytosolic [Ca2+] transients persisted in osteoclasts bathed in Ca(2+)-free, EGTA-containing solutions. They consisted of a peak cytosolic [Ca2+bd elevation followed by a full decay to baseline and were refractory to manipulations of surface membrane potential through changes in extracellular [K+]. They disappeared upon intracellular Ca2+ store depletion through repeated ionophore applications. They were therefore attributable solely to intracellularly stored Ca2+. In contrast, the fura-2 peaks in osteoclasts exposed to Ca(2+)-containing solutions decayed to sustained levels. Cytosolic [Ca2+] responses then persisted with repeated ionomycin application. These latter phenomena are accordingly attributable to extracellular Ca2+ entry. Finally, restoration of extracellular [Ca2+] to 1.25 mM following the depletion of intracellular Ca2+ stores by treatment with ionomycin elicited a cytosolic [Ca2+] 'overshoot' consistent with capacitative Ca2+ entry via a cytosolic route. These results demonstrate a refillable intracellular source of cytosolic Ca2+ that could function in osteoclastic regulation.

Animals↗
PubMed1994

Quantitative studies on the effect of prostacyclin on freshly isolated rat osteoclasts in culture.

Prostaglandins exert marked but transient inhibitory effects on bone resorption. The present study examines the effects of prostacyclin (0.15 to 25 microM) on the morphology of freshly disaggregated rat osteoclasts. An area descriptor, rho, represented changes in total cell spread area, and a motility descriptor, mu, represented overall changes in cell motility. The application of prostacyclin intercepted the trend of an increasing cell spread area with time and produced a transient reduction of rho, an R effect. Its magnitude depended upon concentration and was marked at 25 microM prostacyclin. The subsequent recovery (+0.8/min) of rho at this concentration resembled the persistent spreading seen in the absence of the agonist. There was also a sustained decrease in mu to approximately 60% of its pretreatment value (a Q effect) following the application of 25 microM prostacyclin. The extracellular application of 20 mM [Ca2+] produced a similarly transient cell retraction preceded by a rise of cytosolic [Ca2+], but without a corresponding decrease in mu. In contrast, prostacyclin did not elevate cytosolic [Ca2+], suggesting the triggering of an alternative transduction pathway. A fully reversible retraction together with incomplete quiescence may explain the transience characteristic of the antiresorptive action of prostacyclin.

Animals↗
PubMed1993

Voltage sensitivity of the osteoclast calcium receptor.

We demonstrated previously that osteoclasts possess a divalent cation-sensitive "receptor", the Ca2+ receptor. Activation of the Ca2+ receptor by the surrogate cation Ni2+ was shown to elicit an increase in cytosolic [Ca2+] to a peak value followed by an exponential decline. In the present study we examined the influence of surface membrane voltage on the kinetics of Ca2+ receptor inactivation. The K+ ionophore, valinomycin was applied to intercept the declining phase of the cytosolic [Ca2+] transient elicited by application of between 50 microM- and 5 mM-[Ni2+]. This resulted in a sustained elevation of cytosolic [Ca2+] or even a 'hump' followed by a gradual decline. Such a kinetic alteration persisted in a Ca(2+)-free solution, but was abolished in high extracellular [K+] (105 mM). Thus, we demonstrate for the first time to our knowledge, a modulatory effect of membrane potential on the function of the osteoclast Ca2+ receptor.

Animals↗