scholarly journals Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model

2021 ◽  
Vol 22 (24) ◽  
pp. 13629
Author(s):  
Ola Gutziet ◽  
Roee Iluz ◽  
Hila Ben Asher ◽  
Linoy Segal ◽  
Dikla Ben Zvi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intervention Group ◽  
Study Groups ◽  
Brain Protein ◽  
Protein Levels ◽  
Tnf Α ◽  
Tunel Reaction ◽  
Patients At Risk ◽  
Acetyl Cysteine ◽  
Group 2

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.

Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension

2009 ◽  
Vol 4 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Gad Bar-Joseph ◽  
Yoav Guilburd ◽  
Ada Tamir ◽  
Joseph N. Guilburd
Keyword(s):  
Blood Pressure ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Repeated Measures ◽  
Intervention Group ◽  
Decrease Blood Pressure ◽  
Group 2 ◽  
Group 1

Object Deepening sedation is often needed in patients with intracranial hypertension. All widely used sedative and anesthetic agents (opioids, benzodiazepines, propofol, and barbiturates) decrease blood pressure and may therefore decrease cerebral perfusion pressure (CPP). Ketamine is a potent, safe, rapid-onset anesthetic agent that does not decrease blood pressure. However, ketamine's use in patients with traumatic brain injury and intracranial hypertension is precluded because it is widely stated that it increases intracranial pressure (ICP). Based on anecdotal clinical experience, the authors hypothesized that ketamine does not increase—but may rather decrease—ICP. Methods The authors conducted a prospective, controlled, clinical trial of data obtained in a pediatric intensive care unit of a regional trauma center. All patients were sedated and mechanically ventilated prior to inclusion in the study. Children with sustained, elevated ICP (> 18 mm Hg) resistant to first-tier therapies received a single ketamine dose (1–1.5 mg/kg) either to prevent further ICP increase during a potentially distressing intervention (Group 1) or as an additional measure to lower ICP (Group 2). Hemodynamic, ICP, and CPP values were recorded before ketamine administration, and repeated-measures analysis of variance was used to compare these values with those recorded every minute for 10 minutes following ketamine administration. Results The results of 82 ketamine administrations in 30 patients were analyzed. Overall, following ketamine administration, ICP decreased by 30% (from 25.8 ± 8.4 to 18.0 ± 8.5 mm Hg) (p < 0.001) and CPP increased from 54.4 ± 11.7 to 58.3 ± 13.4 mm Hg (p < 0.005). In Group 1, ICP decreased significantly following ketamine administration and increased by > 2 mm Hg during the distressing intervention in only 1 of 17 events. In Group 2, when ketamine was administered to lower persistent intracranial hypertension, ICP decreased by 33% (from 26.0 ± 9.1 to 17.5 ± 9.1 mm Hg) (p < 0.0001) following ketamine administration. Conclusions In ventilation-treated patients with intracranial hypertension, ketamine effectively decreased ICP and prevented untoward ICP elevations during potentially distressing interventions, without lowering blood pressure and CPP. These results refute the notion that ketamine increases ICP. Ketamine is a safe and effective drug for patients with traumatic brain injury and intracranial hypertension, and it can possibly be used safely in trauma emergency situations.

Effects of Dapagliflozin on Renal Interstitial Fibrosis in Diabetic Rats through Smad3, TIMP1 and MMP24 Pathway

2021 ◽  
Vol 7 (4) ◽  
pp. 690-696
Author(s):  
Yueyao Chen ◽  
Haixiang Li ◽  
Chaoqin Chen
Keyword(s):  
Interstitial Fibrosis ◽  
Intervention Group ◽  
Kidney Tissue ◽  
Diabetic Rats ◽  
Renal Interstitial Fibrosis ◽  
Blank Group ◽  
Protein Levels ◽  
Group A ◽  
Group 3 ◽  
Group 2

Objective: This research was designed to probe into the effects of Dapagliflozin on renal interstitial fibrosis in diabetic rats through Smad3, TIMP1 and MMP24 pathway. Methods: Rats were bought to establish models, and then intervened by Dapagliflozin. Human mesangial cell lines (HMCs) stimulated by high glucose were purchased, and the Smad3, TIMP1 and MMP24 levels in rats after modeling and Dapagliflozin intervention were detected. The Smad3, TIMP1 and MMP24 protein expression in kidney tissue was examined after the rats were killed, and the expression in an intervention group (IG) and a blank group (BG) were analyzed. The cells were divided into three groups: Dapagliflozin intervention (Group 1), TGF-P1/Smad3 pathway inhibitor SIS3 intervention (Group 2) and no intervention (Group 3). The TIMP1 and MMP24 levels were assessed. Results: The Smad3 and MMP24 levels in group A were higher than those in other two groups (p < 0.05), while those of TIMP1 were lower (p < 0.05). Compared with pre-intervention, the Smad3 and MMP24 levels in groups A and B decreased (p < 0.05), while those of TIMP1 increased (p < 0.05). The Smad3 and MMP24 protein levels in groups A and B were higher than those in other two groups (p < 0.05), while those of TIMP1 was lower (p < 0.05). Compared with the BG, the Smad3 and MMP24 expression in the IG was lower (p < 0.05) and that of TIMP1 was higher (p < 0.05). The TIMP1 expression in Group 3 was lower (p < 0.05) and that of MMP24 was higher than those in Groups 1 and 2 (p < 0.05). Conclusion: Dapagliflozin can treat diabetic renal interstitial fibrosis by inhibiting TGF-P1/Smad3 signaling pathway, decreasing MMP24 and increasing TIMP1.

scholarly journals Fresh frozen plasma transfusion in the acute period of isolated traumatic brain injury

2020 ◽  
Vol 17 (5) ◽  
pp. 40-46
Author(s):  
A. I. Baranich ◽  
A. A. Sychev ◽  
N. E. Zakharova ◽  
I. A. Savin ◽  
A. V. Oshorov ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Study Groups ◽  
Fresh Frozen Plasma ◽  
Trauma Outcomes ◽  
Acute Period ◽  
Fresh Frozen ◽  
Severe Tbi ◽  
Group 2 ◽  
Frozen Plasma

Coagulopathy associated with traumatic brain injury (TBI) is recognized as one of the risk factors for poor outcome in patients with TBI, however, the safety of using fresh frozen plasma (FFP) is not fully understood.The objective of the study: to identify the indications for FFP transfusion in the acute period of TBI.Subjects and methods: a retrospective-prospective observational study included 160 patients aged 18-59 years with isolated TBI in the first 48 hours after injury. Patients were assessed by Glasgow Coma Scale (GCS); patients were divided into two study groups: Group 1 – GCS ≤ 8 points, Group 2 – GCS ≥ 9 points. All patients underwent hemostatic assessment with standard clotting tests (activated partial thromboplastin time, prothrombin ratio, fibrinogen blood level). In 42 patients, additional thromboelastometry was performed. Specific parameters of FFP transfusion and trauma outcomes were assessed.Results: according to clotting tests, hypocoagulation was detected in 50.6% of patients; according to thromboelastometry – in 22.7%. FFP was used more often in severe TBI (83%) with a decrease in prothrombin ratio (PR). However, FFP transfusion is associated with an unfavorable outcome: in the case of transfusion, a greater number of deaths and vegetative states were recorded in patients with severe TBI.Conclusion: in patients in the acute period of isolated TBI, it is preferable to minimize the use of FFP; an isolated decrease in PR should not be a trigger for FFP transfusion.

Effect of Mechanical Chest Percussion on Intracranial Pressure: A Pilot Study

2009 ◽  
Vol 18 (4) ◽  
pp. 330-335 ◽  
Author(s):  
DaiWai M. Olson ◽  
Suzanne M. Thoyre ◽  
Stacey N. Bennett ◽  
Joanna B. Stoner ◽  
Carmelo Graffagnino
Keyword(s):  
At Risk ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Intracranial Hypertension ◽  
Intervention Group ◽  
Control Group ◽  
Secondary Brain Injury ◽  
Physical Stimulation ◽  
Patients At Risk ◽  
Injured Patients

Background Treatment of brain injury is often focused on minimizing intracranial pressure, which, when elevated, can lead to secondary brain injury. Chest percussion is a common practice used to treat and prevent pneumonia. Conflicting and limited anecdotal evidence indicates that physical stimulation increases intracranial pressure and should be avoided in patients at risk of intracranial hypertension.Objectives To explore the safety of performing chest percussion for patients at high risk for intracranial hypertension.Methods A total of 28 patients with at least 1 documented episode of intracranial hypertension who were having intracranial pressure monitored were studied in a prospective randomized control trial. Patients were randomly assigned to either the control group (no chest percussion) or the intervention group (10 minutes of chest percussion at noon). Intracranial pressure was recorded once a minute before, during, and after the intervention.Results Mean intracranial pressures for the control group before, during, and after the study period (14.4, 15.0, and 15.9 mm Hg, respectively) did not differ significantly from pressures in the intervention group (13.6, 13.7, and 14.2 mm Hg, respectively).Conclusions Mechanical chest percussion may be a safe intervention for nurses to use on neurologically injured patients who are at risk for intracranial hypertension.

scholarly journals N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice

2021 ◽  
Vol 15 ◽  
Author(s):  
Gagandeep Singh-Mallah ◽  
Takuya Kawamura ◽  
Maryam Ardalan ◽  
Tetyana Chumak ◽  
Pernilla Svedin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Histone Deacetylases ◽  
High Mobility ◽  
Thiol Oxidation ◽  
Neonatal Brain ◽  
Perinatal Brain Injury ◽  
Neonatal Brain Injury ◽  
Protein Levels ◽  
Hypoxia Ischemia ◽  
Acetyl Cysteine

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases. Sirtuin-6 is thought to regulate inflammatory and oxidative pathways, such as the extracellular release of the alarmin high mobility group box-1 (HMGB1). The expression and role of sirtuin-6 in neonatal brain injury are unknown. In a well-established model of neonatal brain injury, which encompasses inflammation (lipopolysaccharide, LPS) and hypoxia-ischemia (LPS+HI), we investigated the protein expression of sirtuin-6 and HMGB1, as well as thiol oxidation. Furthermore, we assessed the effect of the antioxidant N-acetyl cysteine (NAC) on sirtuin-6 expression, nuclear to cytoplasmic translocation, and release of HMGB1 in the brain and blood thiol oxidation after LPS+HI. We demonstrate reduced expression of sirtuin-6 and increased release of HMGB1 in injured hippocampus after LPS+HI. NAC treatment restored sirtuin-6 protein levels, which was associated with reduced extracellular HMGB1 release and reduced thiol oxidation in the blood. The study suggests that early reduction in sirtuin-6 is associated with HMGB1 release, which may contribute to neonatal brain injury, and that antioxidant treatment is beneficial for the alleviation of these injurious mechanisms.

Effect of impaired glucose tolerance during pregnancy on the expression of VEGF receptors in human placenta

2008 ◽  
Vol 20 (7) ◽  
pp. 789 ◽  
Author(s):  
M. Marini ◽  
D. Vichi ◽  
A. Toscano ◽  
G. D. Zappoli Thyrion ◽  
L. Bonaccini ◽  
...  
Keyword(s):  
Study Groups ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Vegf Receptors ◽  
Protein Levels ◽  
Group 3 ◽  
Group 2 ◽  
Endothelial Growth Factor ◽  
Group 1

The aim of the present study was to determine the expression of vascular endothelial growth factor (VEGF) receptors VEGFR-1, VEGFR-2 and VEGFR-3 in placentas from pregnancies complicated by altered glycaemia. Placentas from women with physiological pregnancies (Group 1), pregnancies complicated by minor degree of glucose intolerance (MDGI, Group 2) and by gestational diabetes mellitus (GDM) treated with insulin (Group 3) were collected. Immunohistochemistry, RT–PCR and western blot were employed to evaluate receptor expression. In the three study groups, VEGFR-1 immunoreactivity was detected in all the placental components. VEGFR-2 immunoreactivity was observed in the vessels of all the placentas from Groups 1 and 2, but only in some placentas of Group 3. VEGFR-3 reactivity was observed in all the components of Group 1; in Groups 2 and 3 reactivity was observed in some portions of the trophoblast or the whole trophoblast, and in the stroma. VEGFR-1 and VEGFR-2 mRNA levels in Groups 2 and 3 were significantly higher compared with Group 1, whereas those of VEGFR-3 were significantly lower. Receptor protein levels were significantly lower in Groups 2 and 3 compared with Group 1. These findings demonstrated dysregulation of expression of the three placental receptors, both in GDM and in MDGI.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

scholarly journals A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528 and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1206
Author(s):  
Rafael Guerrero-Bonmatty ◽  
Guadalupe Gil-Fernández ◽  
Francisco José Rodríguez-Velasco ◽  
Jordi Espadaler-Mazo
Keyword(s):  
Intervention Group ◽  
Study Groups ◽  
Statin Treatment ◽  
Blood Cholesterol ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Red Yeast Rice ◽  
Monacolin K ◽  
Double Blind ◽  
History Of

Background: Dietary supplements have been proposed to help manage blood cholesterol, including red yeast rice (RYR) extracts, plant sterols and stanols, beta-glucans, and some probiotics. This study was conducted to evaluate the efficacy of RYR (containing 10 mg of monacolin K) combined with 109 CFU of three Lactoplantibacillus plantarum strains (CECT7527, CECT7528, and CECT7529). Methods: A 12-week randomized, double-blinded, placebo-controlled clinical trial was conducted. In total, 39 adult patients were enrolled, having total cholesterol (TC) ≥200 mg/dL, and being statin-naïve or having recently stopped statin treatment because of intolerance. Active product or placebo were taken once daily, and subjects were evaluated at baseline, 6, and 12 weeks. Results: Study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81% in active vs. 22% in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups and standard error of the mean = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively) upon adjusting for the baseline imbalance in hypercholesterolemia treatment. No adverse effects were noted during the study. Conclusion: This combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.

scholarly journals Skullcapflavone II Suppresses TNF-α/IFN-γ-Induced TARC, MDC, and CTSS Production in HaCaT Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6428
Author(s):  
Hanon Lee ◽  
Dong Hun Lee ◽  
Jang-Hee Oh ◽  
Jin Ho Chung
Keyword(s):  
P38 Mapk ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Mapk Signaling ◽  
Hacat Cells ◽  
Protein Levels ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mapk Signaling Pathways ◽  
Pro Inflammatory Cytokines

Skullcapflavone II (SFII), a flavonoid derived from Scutellaria baicalensis, has been reported to have anti-inflammatory properties. However, its therapeutic potential for skin inflammatory diseases and its mechanism are unknown. Therefore, this study aimed to investigate the effect of SFII on TNF-α/IFN-γ-induced atopic dermatitis (AD)-associated cytokines, such as thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC). Co-stimulation with TNF-α/IFN-γ in HaCaT cells is a well-established model for induction of pro-inflammatory cytokines. We treated cells with SFII prior to TNF-α/IFN-γ-stimulation and confirmed that it significantly inhibited TARC and MDC expression at the mRNA and protein levels. Additionally, SFII also inhibited the expression of cathepsin S (CTSS), which is associated with itching in patients with AD. Using specific inhibitors, we demonstrated that STAT1, NF-κB, and p38 MAPK mediate TNF-α/IFN-γ-induced TARC and MDC, as well as CTSS expression. Finally, we confirmed that SFII significantly suppressed TNF-α/IFN-γ-induced phosphorylation of STAT1, NF-κB, and p38 MAPK. Taken together, our study indicates that SFII inhibits TNF-α/IFN-γ-induced TARC, MDC, and CTSS expression by regulating STAT1, NF-κB, and p38 MAPK signaling pathways.

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