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.

Cerebral Emboli Monitoring Using Transcranial Doppler Ultrasonography in Adults and Children: A Review of the Current Technology and Clinical Applications in the Perioperative and Intensive Care Setting.

Transcranial Doppler (TCD) ultrasonography is the only noninvasive bedside technology for the detection and monitoring of cerebral embolism. TCD may identify patients at risk of acute and chronic neurologic injury from gaseous or solid emboli. Importantly, a window of opportunity for intervention-to eliminate the source of the emboli and thereby prevent subsequent development of a clinical or subclinical stroke-may be identified using TCD. In this review, we discuss the application of TCD sonography in the perioperative and intensive care setting in adults and children known to be at increased risk of cerebral embolism. The major challenge for evaluation of emboli, especially in children, is the need to establish the ground truth and define true emboli identified by TCD. This requires the development and validation of a predictive TCD emboli monitoring technique so that appropriately designed clinical studies intended to identify specific modifiable factors and develop potential strategies to reduce pathologic cerebral embolic burden can be performed.

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.

Identification of work accommodations and interventions associated with work productivity in adults with migraine: A scoping review.

OBJECTIVE: To identify factors associated with work productivity in adults with migraine, and accommodations or interventions to improve productivity or the workplace environment for them. METHODS: We conducted a scoping review by searching MEDLINE, Embase, PsycINFO, Cumulative Index of Nursing and Allied Heath Literature, and Web of Science from their inception to 14 October 2019 for studies of any design that assessed workplace productivity in adults with migraine. RESULTS: We included 26 articles describing 24 studies after screening 4139 records. Five prospective cohort studies showed that education on managing migraine in the workplace was associated with an increase in productivity of 29-36%. Two studies showed that migraine education and management in the workplace were associated with increased productivity (absenteeism decreased by 50% in one study). One prospective cohort study showed that occupational health referrals were associated with more than 50% reduction in absenteeism. Autonomy, social support, and job satisfaction were positively associated with productivity, while quantitative demands, emotional demands, job instability, and non-conducive work environment triggers are negatively associated with productivity in workers with migraine. CONCLUSION: Despite migraine being the second leading cause of disability worldwide, there is a paucity of strong data on migraine-related work factors associated with productivity.Registration: None (scoping review).

Targeting the gut to prevent sepsis from a cutaneous burn.

Severe burn injury induces gut barrier dysfunction and subsequently a profound systemic inflammatory response. In the present study, we examined the role of the small intestinal brush border enzyme, intestinal alkaline phosphatase (IAP), in preserving gut barrier function and preventing systemic inflammation after burn wound infection in mice. Mice were subjected to a 30% total body surface area dorsal burn with or without intradermal injection of Pseudomonas aeruginosa. Mice were gavaged with 2000 units of IAP or vehicle at 3 and 12 hours after the insult. We found that both endogenously produced and exogenously supplemented IAP significantly reduced gut barrier damage, decreased bacterial translocation to the systemic organs, attenuated systemic inflammation, and improved survival in this burn wound infection model. IAP attenuated liver inflammation and reduced the proinflammatory characteristics of portal serum. Furthermore, we found that intestinal luminal contents of burn wound-infected mice negatively impacted the intestinal epithelial integrity compared with luminal contents of control mice and that IAP supplementation preserved monolayer integrity. These results indicate that oral IAP therapy may represent an approach to preserving gut barrier function, blocking proinflammatory triggers from entering the portal system, preventing gut-induced systemic inflammation, and improving survival after severe burn injuries.

Modifications to the PREEMPT Protocol for OnabotulinumtoxinA Injections for Chronic Migraine in Clinical Practice.

OBJECTIVE: To assess the PREEMPT protocol modifications that have developed in clinical practice over time. BACKGROUND: The United States Food and Drug Administration approved the 155-unit fixed-dose, fixed-site PREEMPT protocol of onabotulinumtoxinA (BoNT-A) injections for migraine prevention 9 years ago. METHODS: This is an anonymous survey with free text response options of Headache Medicine clinicians. RESULTS: Out of the 878 contacted Headache Medicine clinicians, 182 (20.7%) completed the survey. Of the 182 respondents, 141 (77.5%) reported that they did not always follow the PREEMPT protocol. Of the 182 respondents, 128 (70%) changed the number of injections, 115 (63%) changed the total units of BoNT-A injected, 105 (57.7%) altered the location of injection sites (58%); 101 (55.5%) do not aspirate to ensure the absence of blood return; 22 (12.1%) changed the dilution; and 4 (2.2%) added lidocaine. The main reported reasons for changes in number, dose, and location of injections included adapting to the patients' pain, anatomy, and preferences. CONCLUSIONS: The wide inter- and intra-personal variations in BoNT-A injections for chronic migraine prevention seen in this survey raise concerns about the standardization of the procedure and suggest that an advisory protocol containing more evidence and discussion of the reasoning behind the recommendations might be more helpful than the current prescriptive protocol.

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.

Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn­site infection.

Burn­site infections, commonly due to Pseudomonas aeruginosa, have been associated with deranged intestinal integrity, allowing bacteria and their products to translocate from the gut to the circulatory system. The P. aeruginosa quorum sensing (QS) transcription factor MvfR (PqsR) controls the expression of numerous virulence factors, and the synthesis of several toxic products. However, the role of QS in intestinal integrity alterations, to the best of our knowledge, has not been previously investigated. Using a proven anti­MvfR, anti­virulence agent, the in vivo results of the present study revealed that inhibition of MvfR function significantly decreased Fluorescein Isothiocyanate­Dextran (FITC­Dextran) flow from the intestine to the systemic circulation, diminished bacterial translocation from the intestine to mesenteric lymph nodes (MLNs), and improved tight junction integrity in thermally injured and infected mice. In addition, the MvfR antagonist administration alleviates the intestinal inflammation, as demonstrated by reduced ileal TNF­α and fecal lipocalin­2 concentrations. In addition, it is associated with lower levels of circulating endotoxin and decreased P. aeruginosa dissemination from the burn wound to the ileum. Collectively, these results hold great promise that the inhibition of this QS system mitigates gut hyperpermeability by attenuating the derangement of morphological and immune aspects of the intestinal barrier, suggesting that MvfR function is crucial in the deterioration of intestinal integrity following P. aeruginosa burn­site infection. Therefore, an anti­virulence approach targeting MvfR, could potentially offer a novel therapeutic approach against multi­drug resistant P. aeruginosa infections following thermal injuries. Since this approach is targeting virulence pathways that are non­essential for growth or viability, our strategy is hypothesized to minimize the development of bacterial resistance, and preserve the beneficial enteric microbes, while improving intestinal integrity that is deranged as a result of burn and infection.

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.

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.

Nitric oxide mediates effects of acute, not chronic, naltrexone on LPS-induced hepatic encephalopathy in cirrhotic rats.

Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.

Intestinal alkaline phosphatase decreases intraperitoneal adhesion formation.

BACKGROUND: Damage to the peritoneum initiates an inflammatory response leading to the formation of adhesions, which subsequently cause significant morbidity in some patients. Intestinal alkaline phosphatase (IAP) is a gut enzyme capable of detoxifying various inflammatory mediators such as lipopolysaccharide, lipoteichoic acid, CpG DNA, and adenosine triphosphate. In this study, we aimed to examine the anti-inflammatory effects of IAP on postoperative adhesions in mice. METHODS: C57BL/6 mice were subjected to a midline laparotomy and then six musculoperitoneal buttons (MPBs) were created by pinching and ligating the peritoneum and underlying muscle. The buttons were half-excised and E-cauterized, and then cecal abrasion was performed. Five hundred microliters of vehicle with IAP 5000 U or vehicle alone were applied over the peritoneal cavity. In some experiments, the mice were euthanized on the first and second postoperative day (POD), and cytokines analysis was done on the MPB, peritoneal tissue, and peritoneal fluid. In separate experiments, the mice were sacrificed on the 21st POD, and adhesion to each button was scored based on type and tenacity. RESULTS: IAP group mice had significantly lower adhesion scores compared with controls (21.5 ± 1.7 versus 13.2 ± 1.3; P = 0.0014, n = 15). MPB from IAP group mice had significantly lower interleukin-1ß and tumor necrosis factor-α protein level compared to control mice (105.66 ± 4.5 versus 69.8 ± 4.8 versus pg/mg, P = 0.0001; 45.25 ± 2.8 pg/mg versus 24.88 ± 4.1 pg/mg; P = 0.0007, n = 10). IAP treatment significantly decreased interleukin-1ß and tumor necrosis factor-α mRNA expression in MPB in the first POD (1.14 ± 0.25 versus 0.33 ± 0.07; P = 0.0068; 1.33 ± 0.31 versus 0.33 ± 0.08; P = 0.0064, n = 10). CONCLUSIONS: Application of IAP during laparotomy could represent a novel approach to prevent postoperative adhesions.

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

Dinitrobenzene sulphonic acid-induced colitis impairs spatial recognition memory in mice: roles of N-methyl D-aspartate receptors and nitric oxide.

RATIONALE: Many peripheral diseases are associated with a decline in cognitive function. In this regard, there have been reports of patients with inflammatory bowel disease and an otherwise unexplained memory impairment. OBJECTIVES: We sought to assess the memory performance of mice with colitis. We also investigated the roles of N-methyl D-aspartate (NMDA) receptors and nitric oxide (NO) as possible mediators of colitis-induced amnesia. METHODS: To induce colitis, male NMRI mice were intrarectally injected with a solution containing dinitrobenzene sulfonic acid (DNBS; 4 mg in 100 µl) under anesthesia. Three days after intrarectal DNBS instillation, spatial recognition and associative memories were assessed by the Y-maze and passive avoidance tasks, respectively. The NMDA antagonists, MK-801 and memantine, and the inducible NO synthase (iNOS) inhibitor, aminoguanidine, were injected intraperitoneally 45 min before the Y-maze task. RESULTS: Induction of colitis by DNBS impaired spatial recognition memory in the Y-maze task but had no effect on step through latencies in the passive avoidance test. Colitis-induced amnesia was reversed by administering specific doses of MK-801 and memantine (30 µg/kg and 1 mg/kg, respectively) suggesting dysregulated NMDA receptor activation as an underlying mechanism. No effect was seen with lower and higher doses of these drugs, resulting in a bell-shaped dose response curve. Colitis-induced amnesia was also inhibited by aminoguanidine (50 mg/kg), implicating a role for iNOS activation and neuroinflammation in this phenomenon. CONCLUSION: DNBS-induced colitis impairs memory through NMDA receptor overstimulation and NO overproduction.

NMDA receptors interact with the retrieval memory enhancing effect of pioglitazone in mice.

PURPOSE: The present study has been undertaken to investigate the possible involvement of the glutamatergic pathway in the beneficial effects of pioglitazone on consolidation and retrieval phases of memory. MATERIALS AND METHODS: The Y-maze task was used to assess short-term spatial recognition memory in animals. Scopolamine (1mg/kg, i.p.) or MK-801 (dizocilpine) (0.03, 0.1 and 0.3mg/kg, i.p.) were administered immediately after the training session to impair memory consolidation or 30min before the retention trial to impair memory retrieval. Pioglitazone (10, 20, 40 and 80mg/kg, p.o.) was administered 2h before the retention session in memory retrieval experiments or immediately after the training session in consolidation experiments. And finally NMDA (N-methyl-d-aspartate) (75mg/kg, i.p) was administered 15min before the administration of pioglitazone. RESULTS: 1) MK-801 (0.3mg/kg) impaired the retrieval of spatial recognition memory. 2) Pioglitazone failed to improve MK-801 induced impairment of retrieval of spatial recognition memory. 3) The 20mg/kg dose of pioglitazone significantly improved memory in mice with scopolamine induced impairment of memory retrieval. 4) Sub-effective dose of MK-801 (0.1mg/kg) was capable of reversing the beneficial effect of pioglitazone on retrieval of memory in scopolamine-treated mice, 5) Administration of NMDA (75mg/kg) and a sub-effective dose of pioglitazone (10mg/kg) reversed the effect of scopolamine and promoted memory retrieval. 6) MK-801 did not affect the consolidation phase of spatial recognition memory. 7) Pioglitazone did not affect scopolamine-induced impairment of memory consolidation. CONCLUSIONS: Sub-effective dose of MK-801 is capable of reversing the protective action of pioglitazone on scopolamine-induced impairment of memory retrieval. Additionally, co-administration of 75mg/kg NMDA and a sub-effective dose of pioglitazone potentiated the effect of pioglitazone on memory retrieval impaired by scopolamine. These results support the idea that pioglitazone plays its memory retrieval enhancement role through the glutamatergic pathway.

A novel approach to maintain gut mucosal integrity using an oral enzyme supplement.

OBJECTIVE: To determine the role of intestinal alkaline phosphatase (IAP) in enteral starvation-induced gut barrier dysfunction and to study its therapeutic effect as a supplement to prevent gut-derived sepsis. BACKGROUND: Critically ill patients are at increased risk for systemic sepsis and, in some cases, multiorgan failure leading to death. Years ago, the gut was identified as a major source for this systemic sepsis syndrome. Previously, we have shown that IAP detoxifies bacterial toxins, prevents endotoxemia, and preserves intestinal microbiotal homeostasis. METHODS: WT and IAP-KO mice were used to examine gut barrier function and tight junction protein levels during 48-hour starvation and fed states. Human ileal fluid samples were collected from 20 patients postileostomy and IAP levels were compared between fasted and fed states. To study the effect of IAP supplementation on starvation-induced gut barrier dysfunction, WT mice were fasted for 48 hours +/- IAP supplementation in the drinking water. RESULTS: The loss of IAP expression is associated with decreased expression of intestinal junctional proteins and impaired barrier function. For the first time, we demonstrate that IAP expression is also decreased in humans who are deprived of enteral feeding. Finally, our data demonstrate that IAP supplementation reverses the gut barrier dysfunction and tight junction protein losses due to a lack of enteral feeding. CONCLUSIONS: IAP is a major regulator of gut mucosal permeability and is able to ameliorate starvation-induced gut barrier dysfunction. Enteral IAP supplementation may represent a novel approach to maintain bowel integrity in critically ill patients.

Gestational diabetes mellitus and iron supplement; effects on pregnancy outcome.

The possible effect of iron supplementation has been investigated in the normal population and patients with gestational diabetes mellitus (GDM). In this study, we survey the risk factors of GDM in pregnant women in contrast with normoglycemic patients in a case control study in patients using iron supplement. This case control study conducted on 52 pregnant women with GDM (25 women with type Al and 27 women with Type A2 of GDM). The control group randomly selected 50 normoglycemic women. Venous blood sampling was done between 24 and 28 weeks of pregnancy for measuring of ferritin, lipoproteins, uric acid and malondialdehyde serum levels. Under study variables including age, gestational age, weight and BMI were gathered. All the women were followed up until the time of delivery and pregnancy outcome were gathered. The serum ferritin levels in GDM group was 31.22+15.44, which is significantly higher than 24.76+8.94, in the control group with (P=0.012). Plasma hemogulobin in the control group was 12.2+0.1 compared to 12.9+0.1 in GDM group which was significantly lower (P=0.005). Triglycerides was significantly higher in GDM group in contrast with the control group, 275.08+143.17 and 192.30+92.13 (P=0.001), respectively. Finally, our findings indicate the concentration of serum ferritin levels was significantly higher in The GDM group.

Antinociceptive and antidiarrheal effects of pioglitazone in a rat model of diarrhoea-predominant irritable bowel syndrome: role of nitric oxide.

Irritable bowel syndrome (IBS) is a prevalent disease characterized by abdominal pain and abnormal bowel habits. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR) γ agonist and, although it is mostly used as an antidiabetic agent, it has been reported to have analgesic effects. Nitric oxide (NO), a gaseous molecule that mediates many of the effects of pioglitazone, has been implicated in the pathophysiology of IBS. The aim of the present study was to investigate the effects of pioglitazone on symptoms in a rat model of diarrhoea-predominant IBS (D-IBS).and to determine the role of NO in these effects. Diarrhoea-predominant IBS was induced by intracolonic instillation of acetic acid. Pioglitazone (2 mg/kg, i.p.) was administered on Days 7, 9 and 11 after acetic acid instillation. To investigate the mechanism involved in pioglitazone action, rats were also administered either the PPARγ antagonist GW9662 (3 mg/kg, i.p.), the NO synthase (NOS) inhibitor N(G) -nitro-l-arginine methyl ester (l-NAME; 10 mg/kg, i.p.) or the NO precursor l-arginine (250 mg/kg, i.p.) along with pioglitazone. Visceral hypersensitivity, nociceptive thresholds, defecation frequency, stool form, serum and colon NO production and inducible (i) NOS activity were assessed 1 h after the final injection of pioglitazone or dimethylsulphoxide (used as the vehicle). Pioglitazone reduced visceral hypersensitivity and defecation frequency, increased nociceptive thresholds, NO production and iNOS activity and shifted stool form towards hard stools in D-IBS rats. These effects of pioglitazone were significantly reversed by l-NAME, but not GW9662. l-Arginine augmented the effects of pioglitazone. In conclusion, pioglitazone alleviates symptoms in a rat model of D-IBS through an NO-dependent mechanism.

Lithium protects against spinal cord injury in rats: role of nitric oxide.

OBJECTIVE: Lithium improves locomotor scores after spinal cord injury (SCI) in rats. However, the underlying mechanisms are unknown. Herein, we assess the role of nitric oxide (NO) in this action. METHODS: The first set of experiments were performed to determine a dose of lithium that effectively improves locomotor scores in rats with SCI. Therefore, rats received different doses of lithium chloride (1, 4, 10, and 20 mg/kg intraperitoneally) or saline 1 hour before SCI. In the next step, the role of NO in the effect of lithium on SCI was investigated. For this purpose, rats were co-treated with an effective dose of lithium (20 mg/kg 1 hour before SCI) and a noneffective dose of Nω-nitro-L-arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor; 15 mg/kg intraperitoneally 30 minutes before SCI). SCI was induced by compressing the T9 spinal segment with an aneurysmal clip for 60 seconds in anesthetized rats. Locomotor scores were determined at 1, 3, 5, 7, 14, 21, and 28 days after SCI. Plasma lithium levels were measured 12 hours after SCI. Spinal histopathologies were examined 30 days after SCI. RESULTS: Lithium (20 mg/kg) significantly improved locomotor scores and decreased histopathologic spinal damage. l-NAME (15 mg/kg) reversed the beneficial effects of lithium. The 20-mg/kg dose of lithium resulted in a 0.68 ± 0.02 mEq/L plasma lithium concentration, which is lower than the therapeutic level in humans (0.8-1.2 mEq/L). CONCLUSION: Lithium protects against SCI through an NO-dependent mechanism.