Significantly Depressed Research Articles

Primary Open Reduction and Internal Fixation of Isolated Compound Depressed Nasal Fractures.

The aim of this study was to assess the efficacy of primary open reduction and internal fixation (ORIF) utilizing the existing dorsal wound for the management of isolated nasal fractures characterized by significant depression and to determine its effectiveness in preventing the need for subsequent nasal revisions. A retrospective review was conducted on patients who underwent ORIF of nasal bone for isolated compound depressed nasal fractures from January 2018 to January 2024. The primary outcomes included the assessment of clinical and radiographic results postoperatively, focusing on nasal symmetry, projection, airway patency, and the incidence of secondary surgical interventions. The study included 15 patients, predominantly males (60%), with an average age of 39.33 years. The mechanisms of injury included motor vehicle accidents (40%), falls (26.7%), interpersonal violence (20%), and occupational injuries (13.3%). All patients were treated on the first (73.3%) or second day (26.7%) after the injury. All patients had satisfactory esthetic and functional outcomes and did not require secondary rhinoplasty. The hardware was removed in 4 patients (26.7%). Primary ORIF through an existing dorsal wound for significantly depressed isolated nasal fractures was effective in obviating the necessity for subsequent nasal revisions.

Effect of Zn2+ and its addition sequence on flotation separation of scheelite from calcite using water glass

Flotation separation of scheelite from calcite remains a challenge because of the presence of Ca active sites on both mineral surfaces and of their similar physicochemical characteristics. In this study, the effect of Zn2+ and its addition sequence on flotation separation of scheelite from calcite was investigated via micro-flotation experiments, zeta potential measurements, solution chemistry calculations, and X-ray photoelectron spectroscopy (XPS) tests. The Zn-water glass (a mixture of Zn2+ and water glass) exhibits a better selective depression effect on calcite than the water glass alone but is much less sensitive to scheelite flotation. However, when Zn2+ is added prior to the water glass, both scheelite and calcite are significantly depressed. The superior selective depression effect of Zn-water glass arises from the selective adsorption of the Zn-silicate polymer and Si(OH)4 on the calcite surface, while the significant non-selective depression effect of Zn2+ added prior to the water glass is due to the adsorption of the hydrophilic Zn species on both scheelite and calcite surfaces.

Histopathological changes and transcriptional alterations of three coagulation factors in zebrafish (Danio rerio) following short-term exposure to MC-LR

Microcystin-LR (MC-LR) is the most common hepatotoxic cyanotoxin produced primarily by Microcystis aeruginosa. Although deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, so far, information on coagulation factors of MC-LR has been rare. In our present study, the effects of MC-LR on the coagulation factors expression and pathological changes in zebrafish were investigated. Adult zebrafish were injected intraperitoneally with 200μg/kg MC-LR and newly hatched larvae were placed in glass wares containing 200μg MC-LR/L, liver and whole larvae were collected after exposure for 12h, 24h, 48h and 96h, respectively. mRNA levels of coagulation factor IX (FIX), coagulation factor VII (FVII) and coagulation factor VIIi (FVIIi) in liver of adult fish and total zebrafish larvae were analyzed using quantitative real-time PCR. Significant depression of FIX and FVII were observed in adult zebrafish at different time point, and FVIIi were also significantly decreased except for 12h post-injection. In addition, the histopathological changes in adult zebrafish liver were observed, and the severe hepatic injuries were found at 96h. The pathological changes further explained the transcriptional results. The transcriptions of FVII were significantly depressed throughout the entire experiment in zebrafish larvae, and the FIX only significantly depressed after exposure for 48 and 96h, however, FVIIi just was significantly reduced after 12h and 24h stimulation. Whatever the mechanism, the effects of MC-LR on the transcription of these coagulation factors might explain the intrahepatic hemorrhage in liver after exposure to MC-LR, and which would provide new information to elucidate the hepatotoxicity of MC-LR.

Incidence of single and mixed infections with Eimeria kofoidi, E. caucasica and E. legionensis on the health of experimentally infected red-legged partridges (Alectoris rufa)

Little is known about Eimeria-induced coccidiosis in partridges. After a coccidiosis outbreak in a farm rearing red-legged partridges (Alectoris rufa) in Brittany (France), three Eimeria species were identified as Eimeria kofoidi, Eimeria caucasica and Eimeria legionensis. This study aimed to reproduce the effects of the disease occurring in field conditions, in the absence of preventive treatments, to further build a coccidiosis model, helpful for coccidiostatic development. The pathogenic effects of a single infection with Eimeria kofoidi, E. caucasica and E. legionensis were evaluated, as well as the effects of multiple infections associating two or three of these species in red-legged partridges. Thirty-one-day-old birds were individually inoculated with Eimeria spp. and clinically followed up until 49 days of age. Mortality, lesion scores, daily oocyst production and growth were used as assessment criteria. Single infections with 250,000 E. kofoidi, 30,000 E. caucasica or 100,000 E. legionensis oocysts did not increase mortality rate compared to uninfected birds, whereas the combination of 3 species caused significant 28% mortality (P<0.05). Five days post inoculation, lesions scores in the proximal intestine (duodenum/jejunum) decreased in dual-infected birds and tended to decrease in triple-infected birds compared to lesions in mono-infected birds. The highest caecal lesion score was recorded in birds co-infected with E. kofoidi and E. legionensis. In multi-infected birds, the total number of oocysts excreted per gram of faeces was lower than the sum of oocysts excreted by mono-infected birds. Each single infection caused significant growth depression and even weight loss in E. legionensis infected birds (P<0.05). Dual or triple infections worsened this effect. Eighteen days post inoculation, only mono-infected birds had recovered. Their weight gains were not different from that of uninfected birds, whereas growth was significantly depressed in dual-infected birds, notably in co-infected E. kofoidi and E. legionensis birds and worsened in triple-infected birds (−34% and −78% growth depression, respectively). Our results indicate that the oocyst doses used were suitable in single infections or should be slightly reduced for future studies requiring significant growth retardation (about 25%). In mixed-infections, the effects on growth are considerably increased; therefore, oocyst doses must be reduced, approximately 125,000 E. kofoidi+15,000 E. caucasica+50,000 E. legionensis oocysts can be recommended. The study model presented here is valuable to conduct further research such as for assessing the ability of these birds to mount immune response against Eimeria spp. or for selecting efficient molecules to struggle coccidiosis of red-legged partridges.

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: A pilot study

IntroductionIt remains unknown why some intubated patients remain infection-free while others develop tracheobronchitis (VAT) or pneumonia (VAP). ObjectiveTo identify and compare VAP/VAT gene expression “signatures” using genome-wide oligonucleotide microarrays. Material and methodsA prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. ResultsEight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the pre-infection period revealed 5595 genes expressed differentially between VAP and VAT (p<0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p<0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. ConclusionIntubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy.

Intubated patients developing tracheobronchitis or pneumonia have distinctive complement system gene expression signatures in the pre-infection period: A pilot study

IntroductionIt remains unknown why some intubated patients remain infection-free while others develop tracheobronchitis (VAT) or pneumonia (VAP). ObjectiveTo identify and compare VAP/VAT gene expression “signatures” using genome-wide oligonucleotide microarrays. Material and methodsA prospective translational study of gene expression profiles of VAP and VAT groups was carried out, establishing comparisons in both pre-infection and infection phases. Pathway and functional analyses were performed with Ingenuity Pathway Analysis (IPA). Data analysis and hierarchical clustering of the genes involved in the signalling pathways expressed differentially in the two groups were performed with GeneSpring GX 11.0. ResultsEight patients developing respiratory infections (3 VAP and 5 VAT) after 4 days of mechanical ventilation were assessed. Comparison of gene expression profiles in the pre-infection period revealed 5595 genes expressed differentially between VAP and VAT (p<0.01, fold change >2). Comparative IPA analysis identified a significant depression of the complement system signalling pathway in the VAP group, affecting the classical pathway along with the final common pathway (p<0.05). In addition, the cAMP and calcium signalling pathways were also significantly depressed in the VAP group during the pre-infection phase also. ConclusionIntubated patients complicated with pneumonia developed immune impairment in the pre-infection period, manifesting as a relatively lower expression of genes involved in the complement system that differed from patients developing tracheobronchitis. These findings suggest that a significant proportion of VAP episodes cannot be prevented, but might be treatable through pre-emptive therapy.

Paradoxical Loss of Sarcoplasmic Reticulum Calcium Release Refractoriness Caused by Overexpressing Calsequestrin in Cardiac Muscle

L-type Ca current (ICa) triggers Carelease from the sarcoplasmic reticulum (SR) by activating RyR2 Ca release channels. Here we probe the role of the SR protein calsequestrin in the regulation of SR Ca2+ release. Voltage-clamped cardiomyocytes loaded with Fluo-4 were stimulated with 1 Hz train (S1 stimuli). Ca2+ release was activated with ICa tail currents to maintain constant trigger. Application of premature extra stimuli (S2) at successively shorter S1-S2 coupling interval resulted in significant depression of Ca2+ release during S2 stimuli in wild-type myocytes. In calsequestrin knockout myocytes (Casq2 KO), the amplitudes of S2 and S1 were the same even at shortest S1-S2 intervals (Figure). This result suggests that calsequestrin is the primary regulator of release refractoriness. To test this hypothesis further, we next used myocytes from calsequestrin overexpressing mice (Casq2 OverX). Casq2 OverX cardiomyocytes exhibit significantly depressed Ca release during S1 transients despite increased SR Ca2+ content. Surprisingly, Ca release amplitudes during the premature S2 stimulus exceeded S1 at short S1-S2 intervals (Figure). Thus, either too little or too much calsequestrin causes loss of SR Ca release refractoriness. Supported by NIH-RO1-HL88635.View Large Image | View Hi-Res Image | Download PowerPoint Slide

A Comparison of the Effects on Respiratory Carbon Dioxide Response, Arterial Blood Pressure, and Heart Rate of Dexmedetomidine, Propofol, and Midazolam in Sevoflurane-Anesthetized Rabbits

Dexmedetomidine, propofol, and midazolam are commonly used sedative-hypnotic drugs. Using a steady-state method, we examined the CO2 ventilatory response, mean arterial blood pressure (MAP) and heart rate (HR) effects of these three drugs in sevoflurane-anesthetized rabbits. New Zealand white rabbits weighing 2.9 +/- 0.2 kg (mean +/- SD) were used. After anesthetic induction and tracheostomy, the animals inhaled 2% sevoflurane to ensure a stable level of sedation throughout the experiment. After preparation, the rabbits were randomly assigned to four groups (n = 10 x 4) and received the following drugs: Group C, control; Group D, dexmedetomidine infused at 2 microg x kg(-1) x h(-1); Group P, propofol with the plasma concentration maintained at 15 microg/mL; Group M, midazolam initial IV 0.3 mg/kg bolus dose, followed by infusion at 1.86 mg x kg(-1) x h(-1). At 15 minutes after the start of infusion, for 20 min periods, in random sequences, gas including 0%, 1%, 2%, 3%, 4%, or 5% of CO2 was delivered to each animal. Fraction of inspired oxygen was maintained at 0.9. We did intergroup comparisons of minute ventilation (MV), respiratory rate, MAP, and HR during the final minute of each inspiratory carbon dioxide concentration (FiCO2) period. For Groups P and M, the rightward shift of plots for MV against FiCO2 indicated significant respiratory depression compared with Group C. There was also significantly more depression than in Group D. We found no significant differences between Groups P and M or between Groups C and D in the plots of MV against FiCO2. No significant differences among the four groups were apparent for respiratory rate. PaCO2-MV response plots were derived from linear regression analysis of data for mean MV and mean PaCO2 at each FiCO2 to compute apneic CO2 thresholds and CO2 sensitivities. The apneic CO2 thresholds of Groups P and M were larger than those of Groups C and D. The CO2 sensitivities of Group D were slightly lower than in Group C. No similar significant difference between the CO2 sensitivities of other group pairs was apparent. MAP in Group D was lower than in Groups C and M. In Group D, HR was lower than in Groups C, P, and M. The major finding is that, during sevoflurane anesthesia in rabbits, dexmedetomidine slightly altered the ventilatory response to CO2. It decreased MAP more than propofol and midazolam, which both significantly depressed the ventilatory response to CO2.

Accumulation of 3H-1-lysine by brain and plasma in male and female rats treated acutely wigh morphine sulfate.

Adult male and female Wistar rats were injected with a single dose of 40 mg/kg of morphine sulfate via indwelling intrajugular cannulas and killed two hours later. 3H-1-lysine was injected at various time intervals before the death of the animals. The distribution of the labelled amino acid was then determined in the free amino acid and lipid-nucleoprotein-extracted protein fractions of plasma and cerebral grey matter. The accumulation of 3H-activity was also determined in various areas of the brain, dorsal root ganglia, pectoral muscle and liver. Morphine-treatment produced an elevation of free 3H-lysine levels in plasma and cerebral grey matter and a decrease in incorporation into protein. A significant sex difference was noted, such that in control males the plasma free 3H-lysine and protein fractions were higher than in females. In the morphine-treated group the values obtained from males were lower than for females. In cerebral grey matter, the free 3H-lysine was significantly lower in control and morphine-treated males than in females. In the protein fraction, such sex differences varied with the time elapsed after injection of amino acid and did not clearly favor either sex. The accumulation of 3H-activity in tissue blocks taken from various regions of CNS was unaffected by morphine-treatment in subcortical components. The values were generally higher in females. 3H-accumulation was significantly altered in cortical components in the male group. In cerebral white matter, the morphine-treated males showed significant elevations of accumulation. Females showed an elevation of 3H-accumulation in the morphine-treated group only when the data was subjected to a group comparison. In the peripheral nervous system, 3H-accumulation was significantly depressed by morphine-treatment only in males. The female values were again significantly higher than those from the males. The male liver demonstrated a significant depression in accumulation of 3H-activity in the morphine-treated group. Liver tissue from females was less responsive and had higher uptakes than in males. Skeletal muscle showed no alteration in 3H-accumulation after morphine treatment in either sex.

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

ObjectiveTo investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies. Study designProspective, blinded, cross-over study. AnimalsSix healthy 5-year-old Shetland ponies. MethodsPonies received either 0.6 mg kg−1 racemic ketamine (group RS) or 0.3 mg kg−1 S-ketamine (group S) intravenously (IV), followed by a CRI of 20 μg kg−1minute−1 racemic ketamine (group RS) or 10 μg kg−1minute−1 S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate. ResultsThe NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL−1 of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9–15 ng mL−1) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5–10 minutes after bolus drug administration in both groups. ConclusionAntinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.

Depression symptomatology and diagnosis: discordance between patients and physicians in primary care settings

BackgroundTo examine the agreement between depression symptoms using an assessment tool (PHQ-9), and physician documentation of the same symptoms during a clinic visit, and then to examine how the presence of these symptoms affects depression diagnosis in primary care settings.MethodsInterviewer administered surveys and medical record reviews. A total of 304 participants were recruited from 2321 participants screened for depression at two large urban primary care community settings.ResultsOf the 2321 participants screened for depression 304 were positive for depression and of these 75.3% (n = 229) were significantly depressed (PHQ-9 score ≥ 10). Of these, 31.0% were diagnosed by a physician with a depressive disorder. A total of 57.6% (n = 175) of study participants had both significant depression symptoms and functional impairment. Of these 37.7% were diagnosed by physicians as depressed. Cohen's Kappa analysis, used to determine the agreement between depression symptoms elicited using the PHQ-9 and physician documentation of these symptoms showed only slight agreement (0.001–0.101) for all depression symptoms using standard agreement rating scales. Further analysis showed that only suicidal ideation and hypersomnia or insomnia were associated with an increased likelihood of physician depression diagnosis (OR 5.41 P sig < .01 and (OR 2.02 P sig < .05 respectively). Other depression symptoms and chronic medical conditions had no affect on physician depression diagnosis.ConclusionTwo-thirds of individuals with depression are undiagnosed in primary care settings. While functional impairment increases the rate of physician diagnosis of depression, the agreement between a structured assessment and physician elicited and or documented symptoms during a clinical encounter is very low. Suicidality, hypersomnia and insomnia are associated with an increase in the rate of depression diagnosis even when physician and self report of the symptom differ. Interventions that emphasize the use of routine structured screening of primary care patients might also improve the rate of diagnosis of depression in these settings. Further studies are needed to explore depression symptom assessment during physician patient encounter in primary care settings.

Differences in LPS and PepG Induced Release of Inflammatory Cytokines in Orthopedic Trauma

Trauma is associated with immune paresis which may predispose to postoperative sepsis. We characterized the ex vivo cytokine responses to bacterial cell wall components in whole blood from 8 patients undergoing a major musculoskeletal trauma in the form of total hip replacement. Preoperatively, at the end of operation, and at days 1 and 6 postoperatively, patient blood was obtained, anticoagulated, and incubated at 37°C in the presence of peptidoglycan (PepG) or lipopolysaccharide (LPS). Plasma cytokines were measured by enzyme immunoassay. The numbers of leucocytes, monocytes, and neutrophils were unchanged at the end of surgery, while there were significant increases at postoperative days 1 and 6. We observed significant reductions in tumor necrosis factor–α (TNF-α) and interleukin 10 (IL-10) responses to PepG at the end of surgery, which was disproportional to the nonsignificant reductions in circulating monocytes, suggesting a functional suppression. However, at postoperative day 1 the responses were recovered. There were no significant changes in responses of TNF-α to LPS stimulation at the end of surgery, while there were significant depressions at postoperative days 1 and 6. The expression of IL-10 was significantly depressed at the end of surgery and at day 6. There were modest changes in PepG- and LPS-induced expression of interleukin 8 (IL-8) during the experiments. On the basis of these observations, we conclude that a musculoskeletal trauma is associated with reduced expression of TNF-α and IL-10 by whole blood leucocytes when exposed to endotoxin, but there is a difference between gram-positive endotoxin (PepG) and gram-negative endotoxin (LPS).

Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia

Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs. Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions. Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol. Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.

Sevoflurane Alters Right Ventricular Performance But Not Pulmonary Vascular Resistance in Acutely Instrumented Anesthetized Pigs

Although the effects of halogenated agents on both normal and diseased left ventricles have been widely studied, the influence of these anesthetic agents on right ventricular (RV) performance remains less well characterized. This study was undertaken to examine the effects of 2 different concentrations of sevoflurane on RV function, and coronary and pulmonary hemodynamics in acutely instrumented anesthetized pigs. Prospective experimental study. Laboratory of experimental research in a university teaching hospital. Anesthetized pigs. Regional RV function in 10 pigs was determined from pressure segment length loop analysis, global RV function from stroke work versus end-diastolic pressure relation, right coronary blood flow, and pulmonary vascular resistance (PVR), without and then with 2.6% (minimum alveolar concentration [MAC]) and 3.9 % (1.5 MAC) end-tidal sevoflurane concentrations. Sevoflurane preserved inflow systolic shortening and RV regional external work, but significantly depressed outflow systolic shortening (p < 0.05). Global RV stroke work was depressed to 72% +/- 12% and 61% +/- 10% of baseline value, respectively, with 1 and 1.5 MAC of sevoflurane (p < 0.05), but without alteration of PVR. Right coronary blood flow decreased dose dependently. Sevoflurane causes significant depression of global RV function associated with a qualitatively different effect on inflow and outflow tracts, without any modification of PVR.

Involvement of Na+/Ca2+ exchanger in catecholamine-induced increase in intracellular calcium in cardiomyocytes

Although sarcolemmal (SL) Na+/Ca2+ exchanger is known to regulate the intracellular Ca2+ concentration ([Ca2+]i), its involvement in catecholamine-induced increase in [Ca2+]i is not fully understood. To gain some information in this regard, isolated rat cardiomyocytes were treated with different agents, which are known to modify Ca2+ movements, in the absence or presence of a beta-adrenoceptor agonist, isoproterenol, and [Ca2+]i in cardiomyocytes was determined spectrofluorometrically with fura-2 AM. Treatment with isoproterenol did not alter [Ca2+]i in quiescent cardiomyocytes, whereas the ATP (purinergic receptor agonist)-induced increase in [Ca2+]i was significantly potentiated by isoproterenol. Unlike ryanodine and cyclopiazonic acid, which affect the sarcoplasmic reticulum function, SL L-type Ca2+ channel blockers verapamil and diltiazem, as well as a SL Ca2+-pump inhibitor, vanadate, caused a significant depression in the isoproterenol-induced increase in [Ca2+]i. The SL Na+/Ca2+ exchange blockers amiloride, Ni2+, and KB-R7943 also attenuated the isoproterenol-mediated increase in [Ca2+]i. Combination of KB-R7943 and verapamil showed additive inhibitory effects on the isoproterenol-induced increase in [Ca2+]i. The isoproterenol-induced increase in [Ca2+]i in KCl-depolarized cardiomyocytes was augmented by low Na+; this augmentation was significantly depressed by treatment with KB-R7943. The positive inotropic action of isoproterenol in isolated hearts was also reduced by KB-R7943. These data suggest that in addition to SL L-type Ca2+ channels, SL Na+/Ca2+ exchanger seems to play an important role in catecholamine-induced increase in [Ca2+]i in cardiomyocytes.

Specific enhancement of sarcomeric response to Ca2+protects murine myocardium against ischemia-reperfusion dysfunction

Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.

Oxidative Stress Due to Nickel Toxicity in the Liver of Protein-Deficient Rats

This study was designed to determine the oxidative stress induced by nickel sulfate in the liver in the protein-deficient rats. Nickel sulfate in the dose of 800 mg/L in drinking water was administrated to Sprauge Dawley (SD) rats as well as protein-deficient rats for a total duration of 8 weeks. The effects of nickel treatment and protein deficiency separately and in combination were studied on rat liver antioxidant defense system enzymes like catalase, glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione-S-transferase (GST), as well as on lipid peroxidation (LPO). The investigations revealed a significant increase in the activity of enzymes, which include catalase, Gpx, GR and GST, and in the levels with LPO following nickel treatment in combination with protein deficiency. On the contrary, feeding to control rats resulted in a significant depression in the levels of SOD and GSH. However, nickel treatment to normal rats caused a significant increase in the activity of enzymes catalase and GST and in the levels of LPO, whereas the levels of GSH get significantly depressed. Further, nickel treatment to protein-deficient rats did not cause any additional alteration in the status of liver antioxidants as were observed in conditions of protein deficiency.

The anti-hyperalgesic effects of carbamazepine and oxcarbazepine are attenuated by treatment with adenosine receptor antagonists

The antinociceptive effects of carbamazepine and oxcarbazepine, and the influence of caffeine, were examined in a paw pressure test in rats. Carbamazepine (10–40 mg/kg; intraperitoneal, i.p.) and oxcarbazepine (40–160 mg/kg; i.p.) caused a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by concanavalin A (Con A), intraplantarly (i.p1.). A comparable pattern of antinociceptive effect of carbamazepine and oxcarbazepine was observed; the only difference is their potency, in that carbamazepine was about three times more potent than oxcarbazepine. Caffeine (5–20 mg/kg; i.p.), a non-selective adenosine receptor antagonist, significantly depressed the antinociceptive effects of carbamazepine and oxcarbazepine, in a dose- and time-dependent manner. Also, a significant depression of the antinociceptive effects of carbamazepine and oxcarbazepine was observed by pretreatment with 1,3-dipropyl-8-cyclopentylxantine (DPCPX, 0.4 and 0.8 mg/kg; i.p.), an adenosine A 1 receptor antagonist. These findings indicate that, in a paw inflammatory hyperalgesia in rats, the antinociceptive effects of both drugs are, at least partially, mediated by adenosine A 1 receptors. In conclusion, the present study suggests the potential clinical importance of carbamazepine and oxcarbazepine in the treatment of inflammatory pain. In addition, caffeine consumption could possibly depress the analgesic effects of both anticonvulsive drugs.

Urocortin does not reduce the renal injury and dysfunction caused by experimental ischaemia/reperfusion

Recent evidence indicates that activators of the serine/threonine kinase pathway protect against ischaemia/reperfusion. Here, we investigate the effects of renal ischaemia/reperfusion on the degree of renal dysfunction and injury with urocortin in rats. Rats treated with urocortin or its vehicle (saline) were subjected to bilateral renal artery occlusion (45 min) and reperfusion (6 h). At the end of experiments, the following indicators and markers of renal injury and dysfunction were measured: plasma urea, creatinine and aspartate aminotransferase, urine flow and creatinine clearance. Urocortin (1 or 15 μg/kg i.v.), administered 5 min prior to reperfusion, was not able to significantly reduce plasma urea, creatinine and aspartate aminotransferase indicating a non-protective effect on the renal dysfunction and reperfusion-injury caused by ischaemia/reperfusion. In addition, 15 μg/kg urocortin significantly depressed urine flow and creatinine clearance, which was associated with a significant depression in mean arterial pressure, indicating reduced renal perfusion. Thus, we propose that the pharmacological application of urocortin does not reduce the renal injury caused by bilateral renal ischaemia/reperfusion.

Frequency specificity of cochlear damage in acute electrical injury: a longitudinal distortion product otoacoustic emission study.

To understand cochlear dysfunction and the recovery pattern of the cochlea after acute electrical injury. The cochlea is believed to be more vulnerable to direct current than to alternating current. However, the damage-and frequency-specific recovery characteristics of the cochlea have not been well described. Baseline distortion product otoacoustic emission measurements were taken via transtympanic electrodes from 19 guinea pigs. A 20-Hz alternating current and a positive direct current, both at a 1,000-microA intensity, were applied to 9 and 10 animals, respectively. The measurements were repeated immediately after the application of current and after 10 days. Comparisons were made for both groups individually in signal-to-noise ratios obtained before and immediately after, immediately and 10 days after, and before and 10 days after the application of electrical current. Alternating and direct currents caused a significant depression in signal-to-noise ratio immediately after the application. However, 10 days later, the mean signal-to-noise ratio in the animals subjected to alternating current came significantly close to the baseline value, particularly between the frequencies of 2,211 and 3,717 Hz. By contrast, the mean signal-to-noise ratio in the animals subjected to direct current remained significantly depressed throughout all frequencies except for 2,211 Hz. Baseline distortion product otoacoustic emission measurements enabled cochlear function to be monitored in a frequency-specific manner after electrical injury. The functional damages were quantitatively close to each other for both types of currents at a given intensity. Nevertheless, recovery was more apparent in the animals exposed to alternating current than in those exposed to direct current. Recovery was also better in the midfrequency region than in higher frequencies. It is hypothesized that the reason for the difference in recovery in both groups was the net charge left by direct current.