Porosity Effects on Static Performance of Carbon Nanotube-Reinforced Meta-Nanocomposite Structures.

A mixture of outstanding merits of polymer nanocomposites (PNCs) and metamaterials can lead to the development of ultra-light meta-nanomaterials whose high sensitivity can be efficiently used in wearable strain sensors. Thus, reliable data about the performance of structural elements manufactured from such meta-nanomaterials are needed before implementing their design. Motivated by this issue, the negative impacts of pores in the microstructure and carbon nanotubes' (CNTs') wavy configuration on the nonlinear bending features of thick beams consisted of auxetic CNT-reinforced (CNTR) polymers are probed for the first time. The impacts of distinct porosity distributions on the mechanical reaction of the system are covered in this article. In addition, a very low computationally cost homogenization is implemented herein to consider the waviness' influence on the reinforcement mechanism in the auxetic PNC material. Moreover, higher-order shear deformation theory (HSDT) is followed and merged with non-linear definition of strain tensor with the aid of von Kármán's theory to gather the equations describing the problem. Thereafter, the famous Navier's exact solution is employed towards solving the problem for thick beams with simple supports at both ends. A comparison of our data with those existing in the literature certifies the accuracy of the presented modeling. The outcomes indicate on the remarkable rise in the flexural deformation of the auxetic PNC beam while the coefficient of porosity is raised. It is also shown that utilization of thick-walled cells in the re-entrant lattice can help to control the system's total deflection. In addition, if the non-ideal shape of the nanofillers is ignored, the deflection of the meta-nanomaterial beam will be much larger than that of ideal calculations.

A clinical decision support system for diagnosing and determining severity of dry eye disease.

INTRODUCTION: Dry eye and its related symptoms are the most common causes of referrals to the ophthalmology centers. Since people with dry eye may suffer from different levels of the disease severity, this study aimed to develop a clinical decision support system for diagnosing and determining severity of dry eye disease. METHODS: This research was carried out in two phases in 2020. In the first phase, a questionnaire was designed to identify the most important diagnostic parameters from the cornea specialists' perspectives (n = 37). In the second phase of the research, a clinical decision support system was designed and implemented by using MATLAB software. Finally, the system was evaluated using patient data which were collected in a teaching hospital (n = 50). RESULTS: The diagnostic parameters for dry eye disease were filamentary keratitis, meibomian gland dysfunction, score of ocular surface disease index, Schirmer's test result, tear meniscus height, tear breakup time, and fluorescein staining score. The system output variables were the diagnosis and severity of dry eye disease at four levels for the right and left eyes, separately. The results of the evaluation study showed that the accuracy, sensitivity and specificity of the system were 96.9%, 97.5%, and 93.7%, respectively. CONCLUSION: It seems that the system designed in this study can help ophthalmologists to diagnose dry eye disease more accurately and quickly. However, it is recommended to conduct more evaluation studies and include more patients in the future research.

Wave Dispersion Behaviors of Multi-Scale CNT/Glass Fiber/Polymer Nanocomposite Laminated Plates.

In this paper, wave propagation in multi-scale hybrid glass fiber (GF)/carbon nanotube (CNT)/polymer nanocomposite plates is studied for the first time by means of refined higher-order plate theory. The hybrid nanocomposite consists of CNTs and glass fibers (GF) as reinforcing components distributed within a polymeric matrix. A hierarchical micromechanical approach is used to predict the effective mechanical properties of the hybrid nanocomposite, including the three-dimensional (3D) Mori-Tanaka method and the rule of mixture. Moreover, a refined-type higher-order shear deformation theory (HSDT) is implemented to take into account the influence of the shear deformation on the motion equations of the system. Then, the governing equations are achieved on the basis of the energy-based Hamilton's principle. Finally, the derived equations will be solved analytically for the purpose of extracting the natural frequency of the continuous system. A set of numerical examples are provided to cover the effects of various parameters on the wave dispersion characteristics of the plate. It can be declared that the hybrid nanocomposite system can achieve higher wave frequencies compared with other types of composite structures. Additionally, it is found that the selection of the lay-ups and length-to-diameter ratio plays a significant role in the determination of the sandwich plate's acoustic response.

Left Ventricular Strain Rate for Intraoperative Evaluation of Cardiac Diastolic Function by Transesophageal Echocardiography: The Correlation Between Late Diastolic Peak Longitudinal Strain Rate and the Severity of Diastolic Dysfunction.

OBJECTIVES: Speckle-tracking echocardiography is a promising tool for evaluating cardiac diastolic dysfunction. A correlation between left atrial strain rate during atrial contraction and the severity of diastolic dysfunction previously has been demonstrated. Because visualization of the left atrial walls is difficult with transesophageal echocardiography, the authors evaluated the use of left ventricular strain rate during atrial contraction as a substitute for left atrial strain rate to intraoperatively measure the extent of cardiac diastolic dysfunction. DESIGN: Retrospective clinical study. SETTING: Single institutional study. PARTICIPANTS: Sixty-six patients who underwent cardiac surgery between January 2018 and January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation of cardiac diastolic dysfunction stage with the peak longitudinal strain rate during late diastole and the time to peak value were evaluated. The late diastolic peak longitudinal strain rate was correlated significantly with the stage of diastolic dysfunction (r = -0.64, p < 0.0001). There was no significant correlation between the stage of diastolic dysfunction and the time to peak value (r = -0.17, p = 0.18). A late diastolic peak longitudinal strain rate <0.68 1/s had a sensitivity of 80% and specificity of 81% for predicting grade 2 or 3 diastolic dysfunction. CONCLUSIONS: The late diastolic peak longitudinal strain rate correlates with the severity of diastolic dysfunction in patients undergoing cardiac surgery.

Speech and language abnormalities in myotonic dystrophy: An overview.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular and multisystem disease that is divided into two types, DM1 and DM2, according to mutations in DMPK and CNBP genes, respectively. DM patients may manifest with various speech and language abnormalities. In this review, we had an overview on speech and language abnormalities in both DM1 and DM2. Our literature search highlights that irrespective of age, all DM patients (i.e. congenital, juvenile, and adult onset DM1 as well as DM2 patients) exhibit various degrees of speech impairments. These problems are related to both cognitive dysfunction (e.g. difficulties in written and spoken language) and bulbar/vocal muscles weakness and myotonia. DM1 adult patients have also a significant decrease in speech rate and performance due to myotonia and flaccid dysarthria, which can improve with warming up. Weakness, tiredness, and hypotonia of oral and velopharyngeal muscles can cause flaccid dysarthria. Hearing impairment also plays a role in affecting speech recognition in DM2. A better understanding of different aspects of speech and language abnormalities in DM patients may provide better characterization of these abnormalities as markers that can be potentially used as outcome measures in natural history studies or clinical trials.

Speckle- Tracking Echocardiography for the Staging of Diastolic Dysfunction: The Correlation Between Strain-Based Indices and the Severity of Left Ventricular Diastolic Dysfunction.

OBJECTIVES: Left ventricular diastolic function can be assessed by various methods. Tissue Doppler imaging is among the most commonly used techniques. However, this imaging is angle- dependent, affected by loading conditions, and susceptible to myocardial tethering. Speckle- tracking echocardiography also can measure strain-based indices to assess diastolic function, and it has fewer limitations than tissue Doppler imaging. Using speckle- tracking echocardiography, the authors evaluated the correlation between the stage of diastolic dysfunction and strain-based indices in patients undergoing cardiac surgery to determine whether strain-based indices can be used intraoperatively to identify the extent of left ventricular diastolic dysfunction. DESIGN: Retrospective clinical study. SETTING: Single university hospital. PARTICIPANTS: Fifty-eight patients undergoing cardiac surgery (December 2017 to December 2019). INTERVENTIONS: None. Measurement and Main Result: Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation between the stage of left ventricular diastolic dysfunction and strain-based indices (including early diastolic peak longitudinal strain and tissue deceleration time) were evaluated. Early diastolic peak longitudinal strain rate significantly correlated with the stage of diastolic dysfunction (r = -0.7 and p < 0.0001). Tissue deceleration time significantly correlated with the stage of diastolic dysfunction in patients with diastolic abnormality (r = -0.4 and p = 0.02). When patients with normal diastolic function were included, this correlation was not significant (r= -0.25 and p = 0.05). CONCLUSIONS: Intraoperatively measured early diastolic peak longitudinal strain rate and tissue deceleration time correlated with the severity of diastolic dysfunction in patients undergoing cardiac surgery.

Intraoperative Assessment of Coronary Artery Stenosis by 2D Speckle-Tracking Echocardiography: The Correlation Between Peak Strain Rate During Early Diastole and the Severity of Coronary Artery Stenosis in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: The effects of inhalation anesthetics on cardiac function and the low correlation between transthoracic and transesophageal echocardiographic measurements may alter the ability of transesophageal echocardiography-derived strain rate during early diastole to detect coronary artery stenosis in anesthetized patients. The authors assessed the correlation between coronary artery stenosis and strain-based parameters during early diastole in heart failure patients with preserved ejection fraction undergoing coronary artery bypass grafting. DESIGN: Retrospective clinical study. SETTING: Single university hospital. PARTICIPANTS: Thirty-two adult patients with preserved ejection fraction undergoing coronary artery bypass grafting between December 2016 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Transesophageal echocardiography images and coronary artery angiographies of the participants were studied. The correlation between the severity of coronary artery stenosis and strain-based indices measured in the corresponding left ventricular segments were assessed. Receiver operating characteristic curve analysis of strain rate during early diastole was used to predict the presence of coronary artery stenosis ≥70%. Regarding the severity of coronary artery stenosis, it demonstrated a strong and inverse correlation with strain rate during early diastole (r = -0.71, p < 0.001), but showed no significant correlation with time to peak strain rate during early diastole (r = 0.19, p = 0.18). Strain rate during early diastole ≤1.5 s-1 had a sensitivity of 77% and a specificity of 87% for predicting coronary artery stenosis ≥70% (area under the curve, 0.88). CONCLUSIONS: Strain rate during early diastole significantly correlates with the severity of coronary artery stenosis in anesthetized patients suffering from heart failure with preserved ejection fraction.

Anesthetic Management of a Patient with a Giant Pericardial Cyst Compressing the Right Atrium.

Pericardial cysts are rare mediastinal cysts composed of a single fluid-filled mesothelial layer and can be congenital in origin or develop secondary to pericarditis, trauma, or infection. Although most pericardial cysts are asymptomatic, life-threatening complications can occasionally occur. We report on a 57-year-old man with an asymptomatic 9 cm pericardial cyst that was incidentally found as an abnormal cardiac silhouette on routine chest radiography. Further imaging confirmed the presence of a pericardial cyst that was compressing the right atrium. The patient underwent successful video-assisted thoracoscopic removal of the pericardial cyst under general anesthesia. The patient's postoperative course was uneventful and he was discharged on postoperative day 1 in a stable condition. To our knowledge, this is the first report regarding the anesthetic management of a patient with a giant pericardial cyst undergoing thoracic surgery. Knowledge regarding the perioperative challenges associated with the removal of pericardial cysts can prevent complications and improve patient outcomes.

Intraoperative assessment of left-ventricular diastolic function by two-dimensional speckle tracking echocardiography: relationship between pulmonary capillary wedge pressure and peak longitudinal strain rate during isovolumetric relaxation in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: Two-dimensional speckle tracking echocardiography has advantages over tissue Doppler imaging during isovolumetric relaxation for predicting left-ventricular end-diastolic pressure in non-surgical patients. Considering the direct and indirect effects of general anesthesia on hemodynamics, we examined correlations between strain-based indices during isovolumetric relaxation and pulmonary capillary wedge pressure in anesthetized patients. Moreover, we determined applicable cut-off values for strain-based indices to predict pulmonary capillary wedge pressure ≥15 mmHg intraoperatively. DESIGN: Retrospective clinical study. SETTING: Single university hospital. PARTICIPANTS: Thirty adult patients with preserved ejection fraction undergoing coronary artery bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-dimensional speckle tracking echocardiography was used to measure strain rate during isovolumetric relaxation (SRIVR) and to calculate the mitral early diastolic inflow (E) to SRIVR ratio (E/SRIVR). Tissue Doppler imaging was used to calculate the E to early diastolic velocity at the lateral mitral annulus ratio (lateral E/e'). SRIVR and E/SRIVR showed strong correlations with pulmonary capillary wedge pressure (r = 0.80 and 0.73, respectively; p < 0.001 and p < 0.001). Lateral E/e' correlated with pulmonary capillary wedge pressure (r = 0.42; p < 0.05). SRIVR predicted high pulmonary capillary wedge pressure better than lateral E/e' did (areas under the receiver operating characteristic curves, 0.94-vs. 0.47, respectively). SRIVR <0.2 s-1 had a sensitivity of 100% and a specificity of 81% for predicting pulmonary capillary wedge pressure ≥15 mmHg. CONCLUSIONS: SRIVR is superior to tissue Doppler indices for predicting pulmonary capillary wedge pressure intraoperatively in patients with coronary artery disease and preserved ejection fraction.

On modeling wave dispersion characteristics of protein lipid nanotubules.

In this article, wave propagation characteristics of protein lipid nanotubules are covered with respect to scale effects utilizing nonlocal strain gradient theory. The structure is supposed to be modeled as a simply supported beam and the kinematic relations are derived based on the classical beam theory (CBT). Implementing an energy based approach, the Euler-Lagrange equations of the lipid tubules are obtained. Moreover, the final governing equations are solved analytically to achieve the wave frequency and phase velocity of propagated waves. Influences of small size and wave number on the wave dispersion responses of lipid nanotubules are shown in detail in different diagrams for both phase velocity and wave frequency. Also, accuracy of introduced model is verified comparing responses of present model with those of former papers.

Anaesthetic management of a patient with a unique combination of anti-N-methyl-D-aspartate receptor encephalitis and stiff-person syndrome.

Stiff-person syndrome (SPS) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are rare paraneoplastic syndromes caused by antibodies that target the central nervous system. Here, we describe a 26-year-old woman who presented with psychosis, amnesia, rigidity and fever. After extensive diagnostic and laboratory workup, she was diagnosed with an ovarian teratoma which was causing the symptoms of anti-NMDAR encephalitis and SPS. The patient was successfully treated with laparoscopic removal of the ovarian tumour under general anaesthesia. She was placed on immunosuppressant medications preoperatively and postoperatively, and her symptoms gradually resolved. Although there are case reports regarding the anaesthetic management of SPS and anti-NMDAR encephalitis, our study is the first report of a patient afflicted with both conditions.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice.

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington>s disease, amyotrophic lateral sclerosis, as well as Alzheimer>s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

Hypothyroidism improves random-pattern skin flap survival in rats.

BACKGROUND: The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. MATERIALS AND METHODS: Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 µg/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. RESULTS: Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% ± 10.49% and 75.48% ± 12.93% versus 52.26% ± 5.75%, respectively, P < 0.01). Acute local treatment of skin flaps with MMI failed to significantly affect the flap survival. CONCLUSION: This study demonstrates for the first time that hypothyroidism improves survival of random-pattern skin flaps in rats.

Local peritoneal irrigation with intestinal alkaline phosphatase is protective against peritonitis in mice.

BACKGROUND: The brush-border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and detoxifies different toll-like receptor ligands. This study aimed to determine the therapeutic effects of locally administered calf IAP (cIAP) in a cecal ligation and puncture (CLP) model of polymicrobial sepsis. METHODS: C57BL/6 mice underwent CLP followed by intraperitoneal injection of cIAP or normal saline. Blood leukocyte counts, levels of cytokines and liver enzymes, and lung myeloperoxidase activity were determined. Peritoneal lavage fluid (PLF) was assayed for neutrophil infiltration and both aerobic and anaerobic bacterial counts. RESULTS: After intraperitoneal injection, cIAP activity in PLF decreased 50% within 15 min with minimal activity evident at 4 h. Compared with irrigation with normal saline, cIAP irrigation increased the 7-day survival rate in mice undergoing CLP, with maximal effects seen at 25 units of cIAP (0% vs. 46% survival rate, respectively; p < 0.001). cIAP treatment reduced lung inflammation, liver damage and levels of tumor necrosis factor alpha and interleukin-6. CONCLUSIONS: Peritoneal irrigation with cIAP significantly enhances survival in a mouse model of peritonitis, likely through reduction of local inflammation and remote organ damage. We suggest that intraperitoneal cIAP irrigation could be a novel therapy for intra-abdominal sepsis.

Intestinal alkaline phosphatase has beneficial effects in mouse models of chronic colitis.

BACKGROUND: The brush border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and is protective against dextran sulfate sodium (DSS)-induced acute injury in rats. The present study evaluated the potential therapeutic role for orally administered calf IAP (cIAP) in two independent mouse models of chronic colitis: 1) DSS-induced chronic colitis, and 2) chronic spontaneous colitis in Wiskott-Aldrich Syndrome protein (WASP)-deficient (knockout) mice that is accelerated by irradiation. METHODS: The wildtype (WT) and IAP knockout (IAP-KO) mice received four cycles of 2% DSS ad libitum for 7 days. Each cycle was followed by a 7-day DSS-free interval during which mice received either cIAP or vehicle in the drinking water. The WASP-KO mice received either vehicle or cIAP for 6 weeks beginning on the day of irradiation. RESULTS: Microscopic colitis scores of DSS-treated IAP-KO mice were higher than DSS-treated WT mice (52±3.8 versus 28.8±6.6, respectively, P<0.0001). cIAP treatment attenuated the disease in both groups (KO=30.7±6.01, WT=18.7±5.0, P<0.05). In irradiated WASP-KO mice cIAP also attenuated colitis compared to control groups (3.3±0.52 versus 6.2±0.34, respectively, P<0.001). Tissue myeloperoxidase activity and proinflammatory cytokines were significantly decreased by cIAP treatment. CONCLUSIONS: Endogenous IAP appears to play a role in protecting the host against chronic colitis. Orally administered cIAP exerts a protective effect in two independent mouse models of chronic colitis and may represent a novel therapy for human IBD.

Chronic lithium impairs skin tolerance to ischemia in random-pattern skin flap of rats.

BACKGROUND: Despite its apparent anti-apoptotic effect, lithium impairs endothelium-dependent vasorelaxation in various tissues. In this study, we assessed the effect of lithium treatment on ischemic skin flap survival and its interaction with nitric oxide pathway. MATERIALS AND METHODS: Seventy-six male Sprague-Dawley rats were randomly assigned into 13 groups. For skin flap surgery, dorsal skin flap measuring 8 × 2 cm was elevated on the midline. After local injections (if needed), the cranial pedicle was cut and flap was sutured back. Flap survival was assessed after 7 d. Animals in the chronic lithium group received lithium chloride in tap water for 4 wk preoperatively and 7 d postoperatively. Acute lithium groups received 3 nmol, 10 nmol and 3 µmol/flap lithium locally. In another experiment, interaction with nitric oxide synthase inhibitor L-NAME as well as nitric oxide precursor L-arginine was studied, and the effect of ischemic preconditioning on skin flap survival in lithium treated rats was investigated. RESULTS: Chronic lithium group had mean flap survival value of 32.6% ± 5.2% (mean ± SD), which was significantly lower than normal subjects (52.7% ± 6.1%, P < 0.001), while acute local lithium treatment had no effect. In chronic lithium group, systemic L-NAME (10 mg/kg, 30 min before flap elevation) failed to significantly decrease the survival, while sub-effective systemic L-arginine (100 mg/kg) and ischemic preconditioning significantly increased flap survival (P < 0.001 and P < 0.01, respectively). CONCLUSIONS: We conclude that long-term lithium treatment impairs the skin tolerance to ischemia in rats, which seems to be nitric oxide mediated. This effect is prevented by ischemic preconditioning or L-arginine treatment. The results suggest that skin-involving interventions should be applied more cautiously in patients who are on lithium treatment.

Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase.

Intestinal alkaline phosphatase (IAP) is a small intestinal brush border enzyme that has been shown to function as a gut mucosal defense factor, but its precise mechanism of action remains unclear. We investigated the effects of IAP on specific bacteria and bacterial components to determine its molecular targets. Purulent fluid from a cecal ligation and puncture model, specific live and heat-killed bacteria (Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes), and a variety of proinflammatory ligands (LPS, CpG DNA, Pam-3-Cys, flagellin, and TNF) were incubated with or without calf IAP (cIAP). Phosphate release was determined by using a malachite green assay. The various fluids were applied to target cells (THP-1, parent HT-29, and IAP-expressing HT-29 cells) and IL-8 secretion measured by ELISA. cIAP inhibited IL-8 induction by purulent fluid in THP-1 cells by >35% (P < 0.005). HT29-IAP cells had a reduced IL-8 response specifically to gram-negative bacteria; >90% reduction compared with parent cells (P < 0.005). cIAP had no effect on live bacteria but attenuated IL-8 induction by heat-killed bacteria by >40% (P < 0.005). cIAP exposure to LPS and CpG DNA caused phosphate release and reduced IL-8 in cell culture by >50% (P < 0.005). Flagellin exposure to cIAP also resulted in reduced IL-8 secretion by >40% (P < 0.005). In contrast, cIAP had no effect on TNF or Pam-3-Cys. The mechanism of IAP action appears to be through dephosphorylation of specific bacterial components, including LPS, CpG DNA, and flagellin, and not on live bacteria themselves. IAP likely targets these bacterially derived molecules in its role as a gut mucosal defense factor.

Cholestasis induces apoptosis in mice cardiac cells: the possible role of nitric oxide and oxidative stress.

BACKGROUND/AIMS: Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts. METHODS: Cholestasis was induced by bile duct-ligation, and sham-operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l-NAME, a non-selective inhibitor of NO synthase, or with d-NAME, an inactive isomer of l-NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined. RESULTS: Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l-NAME, but not d-NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d-NAME treatment. By l-NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l-NAME treatment. CONCLUSION: In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.

ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice.

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. Several studies also suggest a pivotal role for K(ATP) channels in the seizure modulation. The aim of the present study was to evaluate the seizure threshold induced by pentylenetetrazole in diabetic mice at different times (3 days, 1-8 weeks) after induction of diabetes with streptozocin and to examine the possible role of ATP-sensitive potassium (K(ATP)) channels in this manner. Our data showed a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after streptozocin injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The K(ATP) channel opener cromakalim (0.1-30microg/kg, i.p.) significantly increased the seizure threshold in control mice. Although the K(ATP) channel blocker glibenclamide (0.5, 1mg/kg) had no effect, it prevented the effects of the potent dose of cromakalim (30microg/kg) on seizure threshold in control mice. Glibenclamide (1mg/kg, i.p.) also decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with cromakalim (10microg/kg, i.p.). Cromakalim (10microg/kg, i.p.) significantly increased the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1mg/kg, i.p.). We demonstrated a time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. This phenomenon might be due to the probable alteration in the K(ATP) channel functioning during the diabetic condition.

Sildenafil decreased cardiac cell apoptosis in diabetic mice: reduction of oxidative stress as a possible mechanism.

Oxidative stress plays a dominant role in the pathogenesis of cardiac cell apoptosis in diabetic patients. Sildenafil has been demonstrated to have antioxidant effects. In this study, the effects of sildenafil on diabetes-induced cardiac cell apoptosis and the antioxidant status of diabetic mouse hearts were investigated. Diabetic mice showed lower body weight gains and heart weights compared with control mice, and sildenafil treatment did not increase these parameters in diabetic mice. Although apoptotic rates, caspase-3 enzyme activity, and malondialdehyde levels were significantly higher in diabetic mouse hearts than in controls, they were reduced in diabetic mice after sildenafil treatment. At the end of the first week, we observed no significant differences in antioxidant enzyme activities (CAT, GSH-Px, and SOD) in diabetic and control groups, whereas at the end of the second week of sildenafil treatment, antioxidant enzyme activities were higher in the diabetic group. In conclusion, our study indicated that sildenafil was beneficial to hearts of diabetic mice by reducing cardiac cell apoptosis, partially because of its antioxidant effects in the heart.