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1.
Cureus ; 16(5): e59710, 2024 May.
Article in English | MEDLINE | ID: mdl-38841008

ABSTRACT

INTRODUCTION: Preoperative anxiety can negatively impact patient outcomes by influencing the intraoperative requirements for anesthetics and analgesics, increasing postoperative pain intensity, and augmenting the need for analgesia. Moreover, it may contribute to higher rates of postoperative morbidity and mortality following certain types of surgery. This study investigates the anxiolytic and sedative properties of sublingual melatonin as a premedication agent in young females undergoing cesarean section under spinal anesthesia. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in Nasiriyah, Iraq. Eighty females were included, 40 in each group, based on specific inclusion and exclusion criteria. Premedication was administered in the morning, 60 minutes before the procedure. In the melatonin group (M), patients received 10 mg of sublingual melatonin, while the placebo group (P) received placebo premedication. Anxiety and sedation levels were evaluated three times: before taking premedication, five minutes before the insertion of the spinal needle, and one hour postoperatively, using the visual analog scale and Richmond Sedation Scale. RESULTS: The results show a highly significant P-value regarding anxiety levels between the M Group and P Group (p-value < 0.001). There was a significant difference in the median sedation scores between the studied groups at pre-spinal insertion and postoperatively (p-value < 0.001). The mean heart rate in the M Group was significantly lower than in the P Group (p-value = 0.0019). Significant differences were noted in systolic and diastolic blood pressures between the two groups, measured five minutes before and after spinal needle insertion (p-value < 0.001). CONCLUSION: These findings contribute to understanding the impact of sublingual melatonin as an anxiolytic and sedative premedication agent on patients undergoing elective cesarean sections under spinal anesthesia. Further research is warranted to fully elucidate the benefits and implications of melatonin administration in such procedures.

2.
Cureus ; 16(3): e56543, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38646369

ABSTRACT

BACKGROUND: Preoperative anxiety in children has been linked to various postoperative consequences, such as postoperative regressive behavioral issues, extended distress during the recovery period, eating disorders, and bedwetting. The current study aimed to investigate the efficacy of low-dose oral melatonin in alleviating preoperative anxiety among children in the Iraqi population. STUDY DESIGN: A randomized, double-blinded comparative study was undertaken, involving children aged four to 14 years scheduled for elective cardiac catheterization under general anesthesia. The study comprised a total of 80 children. The involved individuals were randomly assigned to two groups, each with 40 subjects. Group A received 0.5 mg/kg melatonin as premedication, while Group B received a placebo. RESULTS: The two groups demonstrated similarity in mean age, weight, cardiac disease, and gender distribution. Statistically significant reductions in anxiety scores were observed in the melatonin group compared to the placebo group. Particularly, children administered 0.5 mg/kg melatonin exhibited the most substantial anxiolysis and venipuncture compliance (P < 0.05). Additionally, children who were premedicated with melatonin experienced decreased cognition, maximum sedation, successful parental separation, and psychomotor impairment (P < 0.05). CONCLUSIONS: Melatonin demonstrated an effective sedation level without significant side effects, making it a preferred choice due to its efficacy, safety, current availability, and cost-effectiveness compared to other anesthetic agents used in premedication procedures.

3.
Saudi J Biol Sci ; 31(4): 103958, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38404537

ABSTRACT

Endophytic fungi that inhabit medicinal plants are microbial resources renowned for having compounds analogous to those produced by their host plants. This study aimed to describe the diversity of endophytic fungi found in Oxalis latifolia Kunth. To better understand the diversity of foliar endophytic fungi found in the leaves of the medicinal plant Oxalis latifolia, we isolated and characterized endophytic by using both morphological and molecular methods employing ITS markers. The antimicrobial activity of endophytic fungi against common human pathogens Escherichia coli, Staphylococcus aureus, and Bacillus subtilis was also investigated. A Total of 16 endophytic fungi were successfully isolated from leaves and classified into five orders of Pezizomycotina based on the phylogenic analyses; Xylariales (56%), Diaporthales (19%) Sordariales (6%), Glomerellales (13%) and Botryosphaeriales (6%). The antimicrobial activity of crude extracts from fungal endophyte against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis revealed that three isolates; N. aurantiaca, Phyllosticta capitalensis N. oryzae were the most potent, while Colletotrichum karstii and N. sphaerica displayed no growth inhibition property against the tested organism. The diversity indices were calculated by using the Shannon-Wiener, Margalef, and Simpson indices. The diversity indices analysis revealed an abundance of species diversity, where the dominant species were Nigrospora oryzae, N. sphaerica, and Colletotrichum karstii. This study describes the diversity of endophytic fungi found in O. latifolia and emphasizes their potential as a source of novel bioactive compounds. More research on phytochemical composition and antimicrobial activity is ongoing to correlate the traditional uses and scientific findings.

4.
Environ Sci Pollut Res Int ; 30(55): 117688-117705, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37867172

ABSTRACT

The treatment and beneficial use of polluted or contaminated environmental matrices have become major issues, especially as the world strives toward a zero-waste policy. In this regard, dredged sediments need to be treated before they can be used in an environmentally safe and sustainable manner. Therefore, this work aims to treat estuarine sediments and, more importantly, use physicochemical, mineral, organic, and chemical information to understand the reactions that occur upon treatment. Dredged estuarine sediments were collected from Tancarville (Seine River estuary, France) and subjected to electrokinetic (EK) remediation using a 128-L laboratory-scale reactor. The sediments were treated 8 h per day for 21 days. The electric (voltage and current) and physicochemical (pH and electric conductivity) parameters were monitored during treatment. Sediments were collected from various sections in the reactor at the end of the experiment (lengthwise, widthwise, and depthwise). The spatial variation was investigated in terms of organic, mineral, and metal contents. Statistical analyses proved that the variation occurred only in the lengthwise direction. Furthermore, three main phases described the treatment, which were mainly linked to carbonate dissolution and pH variation. The results also showed that the trace elements Ni and Zn were reduced by 21% and 19%, respectively, without a direct link to pH, while Ca and Mg were only redistributed. The buffering capacity of the anodic sediment was reduced due to carbonate dissolution. The treated sediments showed reduced contents in trace metals without affecting major elements that can be useful in agriculture (i.e., Ca and Mg).


Subject(s)
Metals, Heavy , Trace Elements , Water Pollutants, Chemical , Trace Elements/analysis , Metals/analysis , Minerals , Agriculture , Carbonates/analysis , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis , Metals, Heavy/analysis
5.
Am J Respir Crit Care Med ; 207(3): 312-322, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36173815

ABSTRACT

Rationale: To date, it remains unclear whether recent changes in the management of patients with systemic sclerosis-associated pulmonary hypertension (SSc-PH) have improved survival. Objectives: To describe a cohort of patients with SSc-PH and compare their characteristics and survival between the last two decades. Methods: Patients with SSc-PH prospectively enrolled in the Johns Hopkins Pulmonary Hypertension Center Registry were grouped into two cohorts based on the date of diagnostic right heart catheterization: cohort A included patients whose disease was diagnosed between 1999 and 2010, and cohort B included those whose disease was diagnosed between 2010 and 2021. Patients' characteristics were compared between the two cohorts. Measurements and Main Results: Of 504 patients with SSc-PH distributed almost equally between the two cohorts, 308 (61%) had World Symposium on Pulmonary Hypertension group 1, 43 (9%) had group 2, and 151 (30%) had group 3 disease. Patients with group 1 disease in cohort B had significantly better clinical and hemodynamic characteristics at diagnosis, were more likely to receive upfront combination pulmonary arterial hypertension therapy, and had a nearly 4-year increase in median transplant-free survival in univariable analysis than those in cohort A (P < 0.01). Improved transplant-free survival was still observed after adjusting for patients' baseline characteristics. In contrast, for group 2 or 3 patients with SSc-PH, there were no differences in baseline clinical, hemodynamic, or survival characteristics between the two cohorts. Conclusions: This is the largest single-center study that compares clinical characteristics of patients with SSc-PH between the last two decades. Transplant-free survival has improved significantly for those with group 1 disease over the last decade, possibly secondary to earlier detection and better therapeutic management. Conversely, those with group 2 or 3 disease continue to have dismal prognosis.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Scleroderma, Systemic , Humans , Pulmonary Arterial Hypertension/therapy , Pulmonary Arterial Hypertension/complications , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/diagnosis , Scleroderma, Systemic/complications , Familial Primary Pulmonary Hypertension/complications , Registries
6.
Cureus ; 14(10): e29908, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36381832

ABSTRACT

BACKGROUND: Recent guidelines report that the administration of tissue plasminogen activator (tPA) within 4.5 hours enhances the clinical outcome of ischemic stroke. We assessed the knowledge and attitude of Sudanese emergency medicine registrars towards the use of tissue plasminogen activators in the management of acute ischemic stroke (AIS). METHODS: This is a descriptive, cross-sectional, hospital-based study. The study was conducted in emergency departments at Khartoum State Hospitals in Sudan during the period from May to July 2021. The study sample was 150 emergency medicine registrars who fulfilled the inclusion criteria of the study. Data was collected by using a self-administered questionnaire as a Google form that was sent to the study participants by email. RESULTS: Knowledge about tPA in the management of AIS at the emergency department was poor, average, and good in 54 (36%), 55 (36.7%), and 41 (27.3%) individuals, respectively. However, there was no significant difference in overall knowledge based on age; nevertheless, good and average knowledge levels were considerably higher among females, level 3 and level 4 of training, and years of experience 5-10 years (p-value = 0.05). The overall attitude of the participants was positive 62 (41.3%), neutral 45 (30%), and negative 43 (28.7%). The positive attitude regarding tPAs for patients with AIS was significantly associated with age 30-40 years, females, levels 3 and 4 of training, and experience 5-10 years (p-value < 0.05). CONCLUSION: The overall knowledge and attitude of emergency medicine registrars were average to good, with a significant proportion of participants reporting low knowledge. The issues encountered by participants in the use of tPAs were the absence of a stroke team in hospitals, the absence of a protocol for the care pathway of AIS management in hospitals, and the absence of tPAs.

7.
J Clin Med ; 11(14)2022 Jul 12.
Article in English | MEDLINE | ID: mdl-35887800

ABSTRACT

Background: Given the morbidity and mortality associated with pulmonary arterial hypertension (PAH), risk stratification approaches that guide therapeutic management have been previously employed. However, most patients remain in the intermediate-risk category despite initial therapy. Herein, we sought to determine whether echocardiographic parameters could improve the risk stratification of intermediate-risk patients. Methods: Prevalent PAH patients previously enrolled in observational studies at 3 pulmonary hypertension centers were included in this study. A validated PAH risk stratification approach was used to stratify patients into low-, intermediate-, and high-risk groups. Right ventricular echocardiographic parameters were used to further stratify intermediate-risk patients into intermediate-low- and intermediate-high-risk groups based on transplant-free survival. Results: From a total of 146 patients included in our study, 38 patients died over a median follow-up of 2.5 years. Patients with intermediate-/high-risk had worse echocardiographic parameters. Tricuspid annular plane systolic excursion (TAPSE) and the degree of tricuspid regurgitation (TR) were highly associated with survival (p < 0.01, p = 0.04, respectively) and were subsequently used to further stratify intermediate-risk patients. Among intermediate-risk patients, survival was worse for patients with TAPSE < 19 mm compared to those with TAPSE ≥ 19 mm (estimated one-year survival 74% vs. 96%, p < 0.01) and for patients with moderate/severe TR compared to those with no/trace/mild TR (estimated one-year survival 70% vs. 93%, p < 0.01). Furthermore, among intermediate-risk patients, those with both TAPSE < 19 mm and moderate/severe TR had an estimated one-year survival (56%) similar to that of high-risk patients (56%), and those with both TAPSE ≥ 19 mm and no/trace/mild TR had an estimated one-year survival (97%) similar to that of low-risk patients (95%). Conclusions: Echocardiography, a routinely performed, non-invasive imaging modality, plays a pivotal role in discriminating distinct survival phenotypes among prevalent intermediate-risk PAH patients using TAPSE and degree of TR. This can potentially help guide subsequent therapy.

9.
ERJ Open Res ; 7(3)2021 Jul.
Article in English | MEDLINE | ID: mdl-34291108

ABSTRACT

RATIONALE: Pulmonary hypertension (PH) is associated with significant perioperative morbidity and mortality. We hypothesised that pulmonary arterial hypertension (PAH) composite risk assessment scores could estimate perioperative risk for PH patients when adjusted for inherent procedural risk. METHODS: We identified patients in the Johns Hopkins PH Center Registry that had noncardiac surgery (including endoscopies) between September 2015 and January 2020. We collected information on preoperative patient-level and procedural variables and used logistic regression to evaluate associations with a composite outcome of death within 30 days or serious postoperative complication. We generated composite patient-level risk assessment scores for each subject and used logistic regression to estimate the association with adverse surgical outcomes. We adjusted multivariable models for inherent procedural risk of major cardiovascular events and used these models to generate a numerical PH perioperative risk (PHPR) score. RESULTS: Among 150 subjects, 19 (12.7%) reached the primary outcome, including 7 deaths (4.7%). Individual patient-level and procedural variables were associated with the primary outcome (all p<0.05). A composite patient-level risk assessment score built on three noninvasive parameters was strongly associated with reduced risk for poor outcomes (OR=0.4, p=0.03). This association was strengthened after adjusting the model for procedural risk. A PHPR score derived from the multivariable model stratified patients into low (0%), intermediate (≤10%), or high (>10%) risk of reaching the primary outcome. CONCLUSION: Composite PAH risk assessment scores can predict perioperative risk for PH patients after accounting for inherent procedural risk. Validation of the PHPR score in a multicentre, prospective cohort is warranted.

11.
World Neurosurg ; 145: e192-e201, 2021 01.
Article in English | MEDLINE | ID: mdl-33045452

ABSTRACT

INTRODUCTION: Blast-induced traumatic brain injuries (bTBIs) are increasingly frequent in civilian settings. We present the first study of individuals with bTBI in Iraq. The study focuses on one of the deadliest suicide car bomb attacks in Iraq and uses it to show the devastating nature of bTBIs. METHODS: This study was conducted at the Neurosurgery Teaching Hospital in Baghdad, Iraq. A retrospective chart analysis of patients with bTBI admitted to the Neurosurgery Teaching Hospital was performed. Measured parameters included patients' demographics, initial presentation, injury patterns, hospital course, surgical management, and outcomes. RESULTS: A total of 75 patients with bTBI were included in this study, 19 of whom died in the emergency room. The remaining 56 patients were admitted to the hospital. Of those patients, 68.6% (n = 39) underwent surgery, and 30.4% were managed conservatively. A modified, tailored triaging system was implemented. All surgery was guided by the principles of damage control neurosurgery. In addition, 76.9% and 46.2% of patients underwent corticectomy and decompressive craniectomy, respectively. Dural venous sinus repair was performed in 17.9% of patients, and 30.7% of the operations entailed additional steps to control major (arterial) cerebrovascular bleeding. The net bTBI-related complication rate was 76%. The total mortality was 48%. Of survivors, 10.7% (n = 8) were discharged with a severe disability. Overall, good outcomes were achieved in 41.3% of the patients. CONCLUSIONS: This study sheds light on the devastating nature of bTBIs. Neurosurgeons worldwide need to be mindful of the unique triaging, diagnostic, and management requirements of these injuries.


Subject(s)
Blast Injuries/pathology , Brain Injuries, Traumatic/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Blast Injuries/etiology , Bombs , Brain Injuries, Traumatic/etiology , Child , Child, Preschool , Female , Humans , Iraq , Male , Middle Aged , Retrospective Studies , Terrorism , Young Adult
12.
Regul Toxicol Pharmacol ; 117: 104768, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32861742

ABSTRACT

Biological medicines have significantly altered treatment for many patients with chronic diseases such as cancers, autoimmune diseases, and diabetes. However, the high cost of biological medicines has limited patients' access to them. Iraq is one of the countries that have decided to increase access to these medicines through biosimilars, which are copies of originator biological medicines. Prior to 2019, the Iraqi National Regulatory Authority (NRA) had no clear guidelines in place for biosimilars uptake. Therefore, approvals of many biosimilars were delayed. As a response to that, a new pivotal committee was found within this authority, and the first version of Iraqi basis and guidelines for the approval of biosimilars was enacted. With the implementation of the Iraqi biosimilars guidelines and escalating the cooperation within the Iraqi NRA, many benefits have been attained in a short time including the approval of many essential biosimilar products which has resulted in a total cost savings estimated to exceed 50 million USD in just the year 2020. However, there are still some barriers towards making the utmost benefit from biosimilars in Iraq, such as lack of familiarity of these products among the Iraqi health care providers which requires appropriate biosimilars-awareness enhancement strategies.


Subject(s)
Biosimilar Pharmaceuticals/standards , Cost Savings/legislation & jurisprudence , Drug Approval/legislation & jurisprudence , Pharmacovigilance , Animals , Biosimilar Pharmaceuticals/economics , Cost Savings/methods , Drug Approval/methods , Humans
13.
BJOG ; 127(3): 416-423, 2020 02.
Article in English | MEDLINE | ID: mdl-31677228

ABSTRACT

OBJECTIVE: To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. DESIGN: Modified Delphi process. SETTING: Participants from 34 countries. POPULATION: Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. METHODS: We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. MAIN OUTCOME MEASURE: Consensus on bundle items. RESULTS: Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. CONCLUSION: A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. TWEETABLE ABSTRACT: A maternal sepsis bundle for low resource settings has been developed by international consensus.


Subject(s)
Patient Care Bundles/methods , Patient Care Management , Pregnancy Complications, Infectious , Consensus , Delphi Technique , Female , Humans , Infant, Newborn , International Cooperation , Medically Underserved Area , Patient Care Management/methods , Patient Care Management/organization & administration , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , World Health Organization
14.
Biomolecules ; 9(8)2019 08 14.
Article in English | MEDLINE | ID: mdl-31416265

ABSTRACT

: Neutrophils undergo a unique form of cell death that generates neutrophil extracellular traps (NETs) that may help to neutralize invading pathogens and restore homeostasis. However, uncontrolled NET formation (NETosis) can result in numerous diseases that adversely affect health. Recent studies further elucidate the mechanistic details of the different forms of NETosis and their common end structure, as NETs were constantly found to contain DNA, modified histones and cytotoxic enzymes. In fact, emerging evidence reveal that the post translational modifications (PTMs) of histones in neutrophils have a critical role in regulating neutrophil death. Histone citrullination is shown to promote a rapid form of NET formation independent of NADPH oxidase (NOX), which relies on calcium influx. Interestingly, few studies suggest an association between histone citrullination and other types of PTMs to control cell survival and death, such as histone methylation. Even more exciting is the finding that histone acetylation has a biphasic effect upon NETosis, where histone deacetylase (HDAC) inhibitors promote baseline, NOX-dependent and -independent NETosis. However, increasing levels of histone acetylation suppresses NETosis, and to switch neutrophil death to apoptosis. Interestingly, in the presence of NETosis-promoting stimuli, high levels of HDACis limit both NETosis and apoptosis, and promote neutrophil survival. Recent studies also reveal the importance of the PTMs of neutrophils in influencing numerous pathologies. Histone modifications in NETs can act as a double-edged sword, as they are capable of altering multiple types of neutrophil death, and influencing numerous NET-mediated diseases, such as acute lung injury (ALI), thrombosis, sepsis, systemic lupus erythematosus, and cancer progression. A clear understanding of the role of different PTMs in neutrophils would be important for an understanding of the molecular mechanisms of NETosis, and to appropriately treat NETs-mediated diseases.


Subject(s)
Extracellular Traps/metabolism , Neutrophils/metabolism , Animals , Histones/metabolism , Humans , Protein Processing, Post-Translational
15.
Biomolecules ; 9(5)2019 05 11.
Article in English | MEDLINE | ID: mdl-31083537

ABSTRACT

Acetylation is an important post translational modification of histone that plays a role in regulation of physiological and pathological process in the body. We have recently shown that the inhibition of histone deacetylases (HDAC) by low concentrations of HDAC inhibitors (HDACis), belinostat (up to 0.25 µM) and panobinostat (up to 0.04 µM) promote histone acetylation (e.g., AcH4) and neutrophil extracellular trap formation (NETosis). Clinical use of belinostat and panobinostat often leads to neutropenia and the in vivo concentrations vary with time and tissue locations. However, the effects of different concentrations of these HDACis on neutrophil death are not fully understood. We considered that increasing concentrations of belinostat and panobinostat could alter the type of neutrophil death. To test this hypothesis, we treated human neutrophils with belinostat and panobinostat in the presence or absence of agonists that promote NOX-dependent NETosis (phorbol myristate acetate or lipopolysaccharide from Escherichia coli 0128) and NOX-independent NETosis (calcium ionophores A23187 or ionomycin from Streptomyces conglobatus). Increasing concentrations of HDACis induced histone acetylation in a dose-dependent manner. ROS analyses showed that increasing concentrations of HDACis, increased the degree of NOX-derived ROS production. Higher levels (>1 µM belinostat and >0.2 µM panobinostat) of AcH4 resulted in a significant inhibition of spontaneous as well as the NOX-dependent and -independent NETosis. By contrast, the degree of neutrophil apoptosis significantly increased, particularly in non-activated cells. Collectively, this study establishes that increasing concentrations of belinostat and panobinostat initially increases NETosis but subsequently reduces NETosis or switches the form of cell death to apoptosis. This new information indicates that belinostat and panobinostat can induce different types of neutrophil death and may induce neutropenia and regulate inflammation at different concentrations.


Subject(s)
Apoptosis , Extracellular Traps/metabolism , Histone Deacetylase Inhibitors/pharmacology , Neutrophils/drug effects , Acetylation , Cells, Cultured , Extracellular Traps/drug effects , Histone Code , Histones/metabolism , Humans , Hydroxamic Acids/pharmacology , Lipopolysaccharides/pharmacology , NADPH Oxidases/metabolism , Neutrophils/metabolism , Panobinostat/pharmacology , Reactive Oxygen Species/metabolism , Sulfonamides/pharmacology , Tetradecanoylphorbol Acetate/pharmacology
16.
Hum Exp Toxicol ; 38(8): 962-973, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31018711

ABSTRACT

OBJECTIVE: To investigate the ability of docosahexaenoic acid (DHA)-loaded silver nanoparticles (AgNPs) in facilitating the incorporation of DHA in the cell membrane, improve cell membrane structure, and attenuate endothelial dysfunction in experimental diabetes. METHODS: DHA/AgNPs were prepared using a nanoprecipitation technique. Fifty male albino rats were used in this study; 10 of them were served as the control group and 40, as the experimental groups, were injected with streptozotocin. Then, the experimental groups were subdivided into diabetic, diabetic treated with DHA, diabetic treated with AgNPs, and diabetic treated with DHA/AgNPs groups. RESULTS: DHA/AgNPs have small spherical size as proved from ultraviolet-visible spectroscopy, transmission electron microscope, dynamic light scattering, and scanning electron microscope techniques. Cell membrane cholesterol and triglycerides showed a significant elevation in the diabetic group compared to the control, but treatment with DHA and DHA/AgNPs caused a significant reduction in both. Treatment with AgNPs and DHA/AgNPs caused a significant improvement in asymmetric dimethylarginine and nitric oxide levels compared to the diabetic group. Cell membrane fatty acids showed that omega-6 polyunsaturated fatty acids (PUFAs) were significantly elevated, while omega-3 PUFA were significantly reduced in the diabetic group compared to the control. There is a significant improvement in the levels of fatty acids in all groups after treatment with DHA, silver, or DHA/AgNPs. CONCLUSION: DHA/AgNPs are potent agents for the improvement of diabetic complication and endothelial dysfunction in experimental diabetes.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Docosahexaenoic Acids/administration & dosage , Metal Nanoparticles/administration & dosage , Silver/administration & dosage , Animals , Arginine/analogs & derivatives , Arginine/metabolism , Aryldialkylphosphatase/blood , Blood Glucose/analysis , DNA Damage , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Docosahexaenoic Acids/chemistry , Insulin/blood , Male , Membrane Lipids/metabolism , Metal Nanoparticles/chemistry , Nitric Oxide/metabolism , Rats, Wistar , Silver/chemistry
17.
Biomolecules ; 9(1)2019 01 18.
Article in English | MEDLINE | ID: mdl-30669408

ABSTRACT

Neutrophils undergo a unique form of cell death to generate neutrophil extracellular traps (NETs). It is well established that citrullination of histones (e.g., CitH3) facilitates chromatin decondensation during NET formation (NETosis), particularly during calcium-induced NETosis that is independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation. However, the importance of other forms of histone modifications in NETosis has not been established. We considered that acetylation of histones would also facilitate NETosis. To test this hypothesis, we induced NOX-dependent NETosis in human neutrophils with phorbol myristate acetate or lipopolysaccharide (from Escherichia coli 0128), and NOX-independent NETosis with calcium ionophores A23187 or ionomycin (from Streptomycesconglobatus) in the presence or absence of two pan histone deacetylase inhibitors (HDACis), belinostat and panobinostat (within their half maximal inhibitory concentration (IC50) range). The presence of these inhibitors increased histone acetylation (e.g., AcH4) in neutrophils. Histone acetylation was sufficient to cause a significant increase (~20%) in NETosis in resting neutrophils above baseline values. When acetylation was promoted during NOX-dependent or -independent NETosis, the degree of NETosis additively increased (~15⁻30%). Reactive oxygen species (ROS) production is essential for baseline NETosis (mediated either by NOX or mitochondria); however, HDACis did not promote ROS production. The chromatin decondensation step requires promoter melting and transcriptional firing in both types of NETosis; consistent with this point, suppression of transcription prevented the NETosis induced by the acetylation of histones. Collectively, this study establishes that histone acetylation (e.g., AcH4) promotes NETosis at baseline, and when induced by both NOX-dependent or -independent pathway agonists, in human neutrophils. Therefore, we propose that acetylation of histone is a key component of NETosis.


Subject(s)
Extracellular Traps/metabolism , Histones/metabolism , Neutrophils/metabolism , Acetylation/drug effects , Histone Deacetylase Inhibitors/pharmacology , Humans , Lipopolysaccharides/pharmacology , Male , Mitochondria/drug effects , Mitochondria/metabolism , NADPH Oxidases/metabolism , Neutrophils/cytology , Neutrophils/drug effects , Reactive Oxygen Species/metabolism , Tetradecanoylphorbol Acetate/pharmacology
18.
Hum Exp Toxicol ; 37(11): 1180-1186, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29441827

ABSTRACT

BACKGROUND: Bronchial asthma is one of the top disabling diseases in pediatrics. Limited research has been studied the association of the widely used plastic monomer bisphenol A (BPA) with childhood asthma. OBJECTIVE: To compare the levels of urinary BPA in asthmatic and control children and to investigate the implication of BPA among other risk factors for the development of asthma. SUBJECTS AND METHODS: This case-control study included 97 children (45 asthmatic and 52 healthy controls) aged 3-8 years. Asthmatic children were diagnosed according to Global initiative for asthma (GINA) guidelines. Sociodemographic factors were assessed and urinary levels of BPA were determined in spot urine samples using high-performance liquid chromatography. The contribution of BPA among predictors for developing asthma was studied in asthmatic children. RESULTS: Median total urinary BPA levels were significantly higher in asthmatic children than in control group (1.56 ng/mL in asthmatic children compared to 0.790 ng/mL in control group, p = 0.001). Children who had total urinary BPA levels >1.3 ng/mL were more likely to be asthmatic (odds ratio: 2.84, 95% confidence interval 1.22-6.59, p = 0.015). Multiple logistic regression analysis for predictors of asthma showed the importance of higher levels of BPA (>1.3 ng/mL) as a more significant predictor than passive smoking ( p = 0.006 for BPA categories vs. p = 0.049 for passive smoking). CONCLUSION: Association of higher levels of urinary BPA with the diagnosis of asthma in children may indicate the potential risk of BPA exposure in the precipitation of bronchial asthma. Further clinical and biochemical research are needed to clarify the proper mechanism explaining this association.


Subject(s)
Asthma/urine , Benzhydryl Compounds/urine , Phenols/urine , Asthma/diagnosis , Asthma/etiology , Biomarkers/urine , Case-Control Studies , Child , Child, Preschool , Chromatography, High Pressure Liquid , Egypt , Female , Humans , Male , Risk Factors , Up-Regulation , Urinalysis
19.
J Genet Eng Biotechnol ; 16(2): 607-612, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30733779

ABSTRACT

Mass propagation of date palm through indirect somatic embryogenesis or organogenesis has attracted the interest of commercial producers. But, this technique still faces some problems that hindered the production of date palm plantlets in vitro. Tissue browning is one of the serious problems that reduce callus growth and shoot regeneration. So the objective of the present study is to investigate the effect of cold pretreatment on callus growth, shoot regeneration, and polyphenol oxidase (PPO) activity during the callus culture. Results showed that a high survival rate of callus cultures (100%) were obtained when cultures were incubated in low temperature (cold treatment) for 45 and 75 days. On the other hand, total amount on phenolic compounds was also reduced to 0.47 and 0.53 mg GAE/g after same period of incubation (45 and 75 days respectively) at low temperature. In additional, our results showed that the highest frequency of shoot formation (66.67 and 73.34, %) and the highest shoot numbers (7.8 and 8.6 shoots/100 mg) were obtained from callus treated with low temperature for 45 and 75 days, respectively.

20.
Methods Mol Biol ; 1637: 119-128, 2017.
Article in English | MEDLINE | ID: mdl-28755341

ABSTRACT

Embryogenic suspension cultures of date palm are ideal for mass propagation of somatic embryos; however, the low percentage of germination of somatic embryos (SE) remains an impediment. This chapter focuses on two important physical factors to improve germination of date palm somatic embryos: the use of partial desiccation (3 h) of somatic embryos and the exposure to low temperature (4 °C for 24 h). High germination percentage (41%) is achieved by desiccation for 3 h. Moreover, adding 0.3 g/L activated charcoal (AC) to the liquid medium further improves somatic embryo number and weight as well as the percentage of germination. Moreover, partial desiccation and low temperature exposure tend to increase proline content. This improved protocol for somatic embryo germination is potentially applicable for commercial micropropagation of date palm.


Subject(s)
Phoeniceae/growth & development , Plant Somatic Embryogenesis Techniques/methods , Cold Temperature , Culture Media/chemistry , Desiccation , Germination , In Vitro Techniques , Organogenesis, Plant , Plant Shoots/growth & development , Regeneration
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