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1.
Pan Afr Med J ; 44: 101, 2023.
Article in English | MEDLINE | ID: mdl-37250673

ABSTRACT

Introduction: vesicovaginal fistula (VVF) is the most common type of urogenital fistula. The laparoscopic approach to VVF repair offers the advantage of minimally invasive surgery with similar principles to the open trans-abdominal approach. The purpose of our study was to evaluate the transperitoneal laparoscopic approach as a minimally invasive tool for VVF repair. Methods: this was a retrospective study including 14 patients with VVF who underwent transperitoneal laparoscopic fistula repair between 2016 and 2020 in the urology department of the university hospital, Kairouan. Patients had undergone surgery at least six months after their primary gynecological surgery and were followed during 9 months after laparoscopic fistula repair. Data regarding patients' characteristics, operative data, and outcomes were gathered. The main outcome was the success rate of VVF closing and postoperative complications. Results: fourteen patients were included. The patient's mean age was 34.8±8.2years. Size of fistula varied from 0.5 to 2cm and all the VVF were supratrigonal. The mean operative time was 145±23.4 minutes with no significant blood loss. The mean hospital stay was 4±1.4 days without major complications. Regarding analgesia, paracetamol was used for the first two days to meet the analgesia needs of all patients, and morphine was used in three cases (21.4%). During follow-up, two patients were re-operated for early recurrence (14.2%) and the total success rate was 85.7% (12 patients). Conclusion: the laparoscopic repair of VVF is a safe, effective, minimally invasive procedure, and without major complications.


Subject(s)
Laparoscopy , Vesicovaginal Fistula , Female , Humans , Adult , Vesicovaginal Fistula/surgery , Retrospective Studies , Feasibility Studies , Laparoscopy/methods , Gynecologic Surgical Procedures/methods , Treatment Outcome
2.
Pak J Pharm Sci ; 34(3): 943-949, 2021 May.
Article in English | MEDLINE | ID: mdl-34602417

ABSTRACT

Allium sativum (As), commonly known as garlic, has been used for a long time, for its therapeutic effects. Recent studies showed the ability of As to modulate vascular activity. The present study aimed to investigate the vasomodulatory effects of aqueous extract of As and to analyse the molecular nature of the active components. Experiments were performed on chick chorioallantoic membrane. Fractions of garlic were directly injected using micropipette on a high vessel density area. Our results clearly indicated that garlic increased permeability and induced vasodilatation of blood vessels and capillaries. These effects were dose-dependent and had been observed just few minutes after the onset of treatment. The active component responsible of these effects, which had a low molecular weight seems to be of peptide nature and appeared different from Dially Sulfide (DAS) and Dially Disulfide (DADS).


Subject(s)
Blood Vessels/drug effects , Capillary Permeability/drug effects , Chorioallantoic Membrane/drug effects , Garlic , Plant Extracts/pharmacology , Vasodilation/drug effects , Animals , Chick Embryo , Chorioallantoic Membrane/blood supply , Chromatography, Thin Layer , Dose-Response Relationship, Drug , Plant Extracts/chemistry
3.
J Chem Neuroanat ; 112: 101915, 2021 03.
Article in English | MEDLINE | ID: mdl-33370573

ABSTRACT

Aluminum (Al) is recognized potent neurotoxic metal, which causes oxidative stress leading to intracellular accumulation of reactive oxygen species (ROS) and neuronal cell death in various neurodegenerative diseases. Among several medicinal plants with beneficial effects on health, curcumin acts as a multi-functional drug with antioxidant activity. Thus, the purpose of the present study was to evaluate the protective effect of curcumin against aluminum induced-oxidative stress and astrocytes death, in vitro ad in vivo. Incubation of cultured rat astrocytes with two concentrations of Al (37 µM and 150 µM) for 1 h provoked a dose-dependent reduction of the number of living cells as evaluated by Fluorescein diacetate and lactate dehydrogenase assay. Al-treated cells exhibited a reduction of both superoxide dismutase (SOD) and catalase activities. Pretreatment of astrocytes with curcumin (81 µM) prevented Al-induced cell death. Regarding in vivo study, rats were exposed acutely during three consecutive days to three different doses of Al (25 mg/kg, 50 mg/kg and 100 mg/kg, i.p injection), together with curcumin treatment (30 mg/kg). For the chronic model, animals were exposed to Al (3 g/l) in drinking water from intrauterine age to 4 months ages, plus curcumin treatment (175 mg/kg). Data showed that both acute and chronic Al intoxication induced an obvious astrogliosis within motor cortex and hippocampus, while, such effects were restored by curcumin. We showed herein that Al was highly toxic, induced astrocytes death. Then, curcumin protected astrocytes against Al-toxicity. The cytoprotective potential of curcumin is initiated by stimulation of endogenous antioxidant system.


Subject(s)
Aluminum/toxicity , Antioxidants/pharmacology , Astrocytes/drug effects , Cell Death/drug effects , Curcumin/pharmacology , Gliosis/chemically induced , Oxidative Stress/drug effects , Animals , Antioxidants/therapeutic use , Astrocytes/pathology , Curcumin/therapeutic use , Gliosis/pathology , Gliosis/prevention & control , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism
4.
Nutr Neurosci ; 24(3): 197-211, 2021 Mar.
Article in English | MEDLINE | ID: mdl-31131731

ABSTRACT

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta, and it involves oxidative stress. Our goal was to evaluate the neuroprotective effect of Vitis vinifera red grape seed and skin extract (GSSE) in a model of Parkinson's disease. GSSE is very rich in phenolic compounds, such as flavonoids, anthocyanins, catechins and stilbenes, which are present in the pulp, seeds, and leaves of the fruit. GSSE is known for its antioxidant properties and has shown beneficial effects against oxidative injury in different organs, such as the kidneys, liver, heart and brain. In this study, we revealed the neuroprotective effect of GSSE on midbrain dopaminergic neurons both in vitro and in vivo. We used the neurotoxin 6-hydroxydopamine (6-OHDA), which induces oxidative damage and mimics the degeneration of dopaminergic neurons observed in Parkinson's disease. We found that GSSE was effective in protecting dopamine neurons from 6-OHDA toxicity by reducing apoptosis, the level of reactive oxygen species (ROS) and inflammation. Furthermore, we found that GSSE treatment efficiently protected against neuronal loss and improved motor function in an in vivo 6-OHDA model of Parkinson's disease (PD). Altogether, our results show that GSSE acts at multiple levels to protect dopamine neurons from degeneration in a model of PD.


Subject(s)
Grape Seed Extract/administration & dosage , Neuroprotective Agents/administration & dosage , Parkinson Disease/metabolism , Parkinson Disease/pathology , Vitis , Animals , Apoptosis/drug effects , Disease Models, Animal , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/pathology , Male , Mice , Oxidative Stress/drug effects
5.
Acta Biomed ; 91(3): ahead of print, 2020 07 13.
Article in English | MEDLINE | ID: mdl-32921748

ABSTRACT

Type 1 diabetes mellitus (T1DM) is rare in infants and toddlers and is usually associated with a relatively high mortality when complicated with diabetic ketoacidosis (DKA). In infants, the classical symptoms of DKA are atypical and therefore many infants with DKA are mistreated for infections. We report a case of DKA precipitated by COVID-19 in an 8-month-old infant with newly diagnosed diabetes mellitus. This case is reported in view of its rarity and originality. The relation between T1DM and COVID19 infection is discussed.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Diabetes Mellitus, Type 1/complications , Diabetic Ketoacidosis/etiology , Pneumonia, Viral/complications , Biomarkers/blood , Blood Glucose/metabolism , COVID-19 , Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Infant , Insulin Detemir/therapeutic use , Male , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
6.
J Med Food ; 23(10): 1077-1082, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32109173

ABSTRACT

Although progress has been made to show the role of raw flaxseed and flaxseed extracts in health promotion, identification of mechanism(s) of action and molecule(s) underpinning beneficial effects largely remain unknown. The present study evaluated the efficacy of an aqueous flaxseed extract (AFE) to correct alloxan-induced diabetes in mice. Mice were divided into five groups: one nondiabetic (negative control) and four diabetic. Diabetic mice were treated with AFE, gallic acid (GA) (major component of AFE), insulin (positive control), or remained untreated (positive control). Oral administration of AFE strongly improved serum glucose, oral glucose tolerance, insulin tolerance, body weight, and polyphagia in diabetic mice. AFE was effective in controlling lipid peroxidation (thiobarbituric acid-reactive substances) and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in liver and kidney, which undergo diabetes-related complications due to hyperglycemia. These results demonstrated that GA alone was sufficient to account for the beneficial health effects of AFE against diabetes.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Flax/chemistry , Hypoglycemic Agents/therapeutic use , Plant Extracts/therapeutic use , Alloxan , Animals , Antioxidants/metabolism , Blood Glucose , Diabetes Mellitus, Experimental/chemically induced , Mice , Oxidative Stress , Seeds/chemistry
7.
J Sports Med Phys Fitness ; 60(1): 45-52, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31640314

ABSTRACT

BACKGROUND: This study aims to determine the effect of flexibility exercises combined with plyometrics in hurdles race, on physical fitness, motor skills (MS) and hip range of motion. METHODS: Thirty-four male hurdlers, (age=15.7±0.7 years, body mass=59.7±2.3 kg, height=170.8±2.4 cm) were randomly assigned to four independent groups. The (Gflex+plyo), the (Gplyo), the (Gflex) and a control group (Gcon). All participants performed different tests: a test of right and left hip flexion (RHF, LHF) and extension (RHE, LHE), squat jump (SJ), countermovement jump (CMJ), stiffness jump (STFJ) and three (MS) exercises (running, hopping and leaping). A 60-m sprint on the hurdles was also performed. RESULTS: The two-way analyses of covariance for repeated measures showed that Gflex+plyo increased significantly: the CMJ, performance on 60-m and showed higher performance in the between groups' comparison. The Gflex+plyo and Gflex showed the higher percentages of changes in flexibility (RHF: 3.2±1.3% and 3.0±2.1%; RHE: 6.4±2.4% and 9.4±4.1%, LHE: 8.4±3.4% and 7.8±4.3%, respectively). Gplyo increased significantly the LHF (3.9±1.4%) more than the other groups. In the between groups' comparison, Gplyo showed the higher percentage of change in STFJ (6.4±1.8%) and the Gflex+plyo showed the higher values in running and hopping (10.7±4.6% and 13.3±2.1%, respectively). CONCLUSIONS: Specific stretching exercises combined with plyometrics may be more beneficial than other training strategies in young sprint-hurdlers. This may better improve physical fitness, hip range of motion and may increase different level of skills which may better improve performance in hurdles race.


Subject(s)
Muscle Stretching Exercises/methods , Plyometric Exercise/methods , Track and Field/physiology , Adolescent , Case-Control Studies , Humans , Male , Physical Fitness/physiology , Random Allocation , Range of Motion, Articular/physiology , Running/physiology
8.
Tunis Med ; 97(5): 667-674, 2019 May.
Article in English | MEDLINE | ID: mdl-31729738

ABSTRACT

AIM: Percutaneous nephrolithotomy (PCNL) remains the standard procedure for large (≥2 cm) renal calculi; however, up to one quarter of PCNL patients experience some perioperative complications. The aim of the present study was to investigate the factors that may influence bleeding and fever following percutaneous nephrolithotomy. METHODS: In total, 170 patients, who underwent percutaneous nephrolithotomy between January 2012 and January 2016 in our Urology department, were retrospectively evaluated for postoperative bleeding and fever. Preoperative, operative and postoperative factors were assessed using univariate followed by multivariate regression. RESULTS: The mean patient age was 49.41 ± 15.07 years (14-83). The overall stone-free rate was 83.5%. We recorded 48 postoperative complications (28.2%): 34 cases of fever and 14 cases of bleeding. Univariate analyses showed an association between diabetes and postoperative bleeding (p=0.002). Staghorn calculus (p=0.0001), prone position (p=0.009), operative time (p=0.0001) and presence of residual stones ≥  7 mm were associated to postoperative fever (p=0.01). Multivariate stepwise regression analyses showed that diabetes was the only independent predictive factor of postoperative bleeding (OR=7.6). Staghorn lithiasis (OR=5.9), prone position (OR=3.7) and operative time > 95 minutes (OR=6.2) were the predictive factors of postoperative fever. CONCLUSIONS: To our knowledge, this study is the first to report that prone position was significantly associated with fever after percutaneous nephrolithotomy. Further studies are necessary to confirm our results in a greater number of patients.


Subject(s)
Fever/epidemiology , Kidney Calculi/surgery , Nephrolithotomy, Percutaneous , Postoperative Complications/epidemiology , Postoperative Hemorrhage/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Young Adult
9.
Tunis Med ; 97(1): 100-105, 2019 Jan.
Article in English | MEDLINE | ID: mdl-31535700

ABSTRACT

INTRODUCTION: Cadmium (Cd) is a toxic heavy metal used in various industrial applications and therefore can cause, both by environmental or professional exposure, several damage in all body systems. The present study was developed to determine the toxic effect of high dose of Cd on the rat's liver as well as the putative protective effect of vitamin E. METHODS: During the experiment, rats were administrated Cd per orally (PO) (15mg/Kg bw) alone or associated with an intraperitonial (IP) injection of alphatocopherol (Vitamin E) (300mg/Kg / day) for three weeks. We analyzed the effect of vitamin E on Cd induced liver remodeling by hematoxylin-eosin staining (HE), and by the determination of the antioxidant profiles and lipid peroxidation in rats's livers. RESULTS: Data confirmed that high dose of cd induced a loss of the liver weight and a pro-oxidative state into hepatocytes characterized by increased malondialdehyde (MDA) and peroxidase (POD), no changes in catalase (CAT) and a decrease on the superoxide dismutase (SOD) activities. These disturbances may be explained by a decrease in the level of hepatic calcium (Ca). Co-treatment with Vitamin E, decreased MDA and POD activities, increased CAT and SOD activities and restored Ca level. All these corrections were accompanied by an improvement of the liver 's structure. CONCLUSION: Our results suggest that Cd induced an oxidative stress into rat liver and Vitamin E exerted antioxidant properties which can be mediated by the modulation of Ca level.


Subject(s)
Cadmium/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Oxidative Stress/drug effects , Vitamin E/pharmacology , Animals , Antioxidants/pharmacology , Catalase/drug effects , Catalase/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cytoprotection/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Lipid Peroxidation/drug effects , Liver/metabolism , Liver/pathology , Male , Protective Agents/pharmacology , Rats , Rats, Wistar
10.
Cardiovasc Res ; 115(2): 463-475, 2019 02 01.
Article in English | MEDLINE | ID: mdl-29982533

ABSTRACT

Aims: The term angiogenesis refers to sprouting of new blood vessels from pre-existing ones. The angiogenic process involves cell migration and tubulogenesis requiring interaction between endothelial cells and the extracellular matrix. Human peroxidasin 1 (hsPxd01) is a multidomain heme peroxidase found embedded in the basement membranes. As it promotes the stabilization of extracellular matrix, we investigated its possible role in angiogenesis both in vitro and in vivo. Methods and results: We analysed the effects of peroxidasin 1 gene silencing and supplementation by recombinant hsPxd01 in TeloHAEC endothelial cells on cell migration, tubulogenesis in matrigel, and intracellular signal transduction as assessed by kinase phosphorylation and expression of pro-angiogenic genes as measured by qRT-PCR. We further evaluated the angiogenic potential of recombinant peroxidasin in a chicken chorioallantoic membrane model. RNA silencing of endogenous hsPxd01 significantly reduced tube formation and cell migration, whereas supplementation by the recombinant peroxidase promoted tube formation in vitro and stimulated vascularization in vivo through its catalytic activity. Moreover, recombinant hsPxd01 promoted phosphorylation of Extracellular signal-Regulated Kinases (ERK1/2), Protein kinase B (Akt), and Focal Adhesion Kinase (FAK), and induced the expression of pro-angiogenic downstream genes: Platelet Derived Growth Factor Subunit B (PDGFB), endothelial-derived Heparin Binding EGF-like growth factor (HB-EGF), CXCL-1, Hairy-Related Transcription Factor 1 (HEY-1), DNA-binding protein inhibitor (ID-2), Snail Family Zinc Finger 1 (SNAI-1), as well as endogenous hsPxd01. However, peroxidasin silencing significantly reduced Akt and FAK phosphorylation but induced ERK1/2 activation after supplementation by recombinant hsPxd01. While hsPxd01 silencing significantly reduced expression of HEY-1, ID-2, and PDGFB, it did not affect expression of SNAI-1, HB-EGF, and CXCL-1 after supplementation by recombinant hsPxd01. Conclusion: Our findings suggest a role of enzymatically active peroxidasin 1 as a pro-angiogenic peroxidase and a modulator of ERK1/2, Akt and FAK signalling.


Subject(s)
Endothelial Cells/enzymology , Focal Adhesion Kinase 1/metabolism , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neovascularization, Physiologic , Peroxidases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Chick Embryo , Enzyme Activation , Gene Expression Regulation , Humans , Peroxidases/genetics , Phosphorylation , Signal Transduction
11.
J Mol Neurosci ; 69(1): 1-16, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30343367

ABSTRACT

Oxidative stress, associated with various neurodegenerative diseases, promotes ROS generation, impairs cellular antioxidant defenses, and finally, triggers both neurons and astroglial cell death by apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). We have previously reported that ODN acts as a potent neuroprotective agent that prevents 6-OHDA-induced apoptotic neuronal death. The purpose of the present study was to investigate the potential glioprotective effect of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Incubation of astrocytes with graded concentrations of ODN (10-14 to 10-8 M) inhibited 6-OHDA-evoked cell death in a concentration- and time-dependent manner. In addition, ODN prevented the decrease of mitochondrial activity and caspase-3 activation induced by 6-OHDA. 6-OHDA-treated cells also exhibited enhanced levels of ROS associated with a generation of H2O2 and O2°-, and a reduction of both superoxide dismutase (SOD) and catalase (CAT) activities. Co-treatment of astrocytes with low concentrations of ODN dose-dependently blocked 6-OHDA-evoked production of ROS and inhibition of antioxidant enzyme activities. Concomitantly, ODN stimulated Mn-SOD, CAT, glutathione peroxidase-1, and sulfiredoxin-1 gene transcription and rescued 6-OHDA-associated reduced expression of endogenous antioxidant enzymes. Taken together, these data indicate that, in rat astrocytes, ODN exerts anti-apoptotic and anti-oxidative activities, and hence prevents 6-OHDA-induced oxidative assault and cell death. ODN is thus a potential candidate to delay neuronal damages in various pathological conditions involving oxidative neurodegeneration.


Subject(s)
Antioxidants/pharmacology , Apoptosis , Astrocytes/drug effects , Diazepam Binding Inhibitor/pharmacology , Neuropeptides/pharmacology , Neuroprotective Agents/pharmacology , Peptide Fragments/pharmacology , Animals , Astrocytes/metabolism , Caspase 3/metabolism , Catalase/metabolism , Cells, Cultured , Oxidopamine/toxicity , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
12.
Int J Surg Case Rep ; 53: 345-347, 2018.
Article in English | MEDLINE | ID: mdl-30471627

ABSTRACT

INTRODUCTION: Polyorchidism, defined as the presence of more than two testicles, is a rare congenital abnormality of the male genital tract. There is no consensus regarding the management of supranumerary testis (SNT) due to its rareness. To the best of our knowledge, this is the first report of leiomyoma in SNT. PRESENTATION OF CASE: We report the case of a 41-year-old man with two right testes sharing a common vas deferens and separate epididymides. Orchiectomy of right testes was performed. Pathology examination found that the superior testis was the site of a leiomyoma and the lower tesits was the site of an intratubular germ cell neoplasia (IGCN). Orchiopexy and biopsy were later performed for the left testis. Histology was compatible with IGCN. We opted for follow-up to avoid risks of hypogonadism. DISCUSSION: Polyorchidism is usually asymptomatic and found incidentally during surgery for inguinal hernia, undescended testes as in our case, torsion, hydrocele or testicular tumor. If the SNT is scrotal, and there is no other indication for surgery, most authors recommend conservative management with regular ultrasound follow-up. If nonscrotal SNT is found incidentally during surgery, orchiectomy could be performed because of increased risk of malignancy. Treatment of IGCN includes surveillance, orchiectomy, or low-dose external radiation. CONCLUSION: Different factors come into account for polyorchidsm management: the drainage system, the fertile potential of the supernumerary gonad, and its localization. In cases of uncomplicated polyorchidism, a conservative treatment, with US or MRI follow-up seems to be a rational choice without surgical complications.

13.
Tunis Med ; 96(6): 391-392, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30430479

ABSTRACT

Urethral diverticulum of the male is uncommon. We report a case of bulbar urethraldiverticulum with contained giant calculus presenting as left inguino-scrotal swellingsecondary to peri-urethral abscess in a 40 year-old male. In the light of this case Weemphasize the importance of investigation for the presence of urethral diverticulum in youngmale individuals presenting with voiding disturbances to preventrelated complications.


Subject(s)
Abscess/diagnosis , Diverticulum/diagnosis , Urethral Diseases/diagnosis , Urinary Calculi/diagnosis , Abscess/pathology , Adult , Diverticulum/pathology , Humans , Male , Scrotum/pathology , Urethral Diseases/pathology , Urinary Calculi/pathology
14.
Curr Pharm Des ; 24(33): 3918-3925, 2018.
Article in English | MEDLINE | ID: mdl-30417780

ABSTRACT

The term endozepines designates a family of astroglia-secreted proteins including the diazepambinding inhibitor (DBI) and its processing products, which have been originally isolated and characterized as endogenous ligands of benzodiazepine receptors. It is now clearly established that the octadecaneuropeptide ODN (DBI33-50), acting through the central-type benzodiazepine receptor or a metabotropic receptor, exerts important functions such as proconflict behavior, induction of anxiety, inhibition of pentobarbital-provoked sleep, decrease of water consumption and reduction of food intake. To mediate its effects, ODN regulates both glial cell and neuronal activities by acting on neurosteroid biosynthesis and/or neuropeptide expression. In addition, ODN stimulates astrocyte proliferation and protects both neurons and astrocytes from oxidative stress-induced cell death. The antiapoptotic effect of ODN on neural cells is mediated through activation of the ODN metabotropic receptor positively coupled to PKA, PKC and MAPK/ERK transduction pathways, which ultimately reduces the pro-apoptotic gene Bax and stimulates Bcl-2 expressions, and inhibits intracellular reactive oxygen species accumulation. The imbalance in favor of Bcl2 promotes mitochondria functions and blocks in turn caspases activation while at the same time, ODN also activates the endogenous antioxidant system i.e. glutathione biosynthesis, and expression and activities of antioxidant enzymes. In cultured astrocytes, DBI expression is up-regulated during moderate oxidative stress, and authentic ODN production is increased, suggesting that ODN may act as a paracrine factor protecting neighboring neurons. Taken together, the remarkable effect of ODN on the apoptotic cascade suggests that innovative ODN derivatives could potentially be useful for treatment of cerebral injuries involving oxidative stress and neurodegeneration.


Subject(s)
Brain Injuries/drug therapy , Diazepam Binding Inhibitor/pharmacology , Neurons/drug effects , Neuropeptides/pharmacology , Neuroprotection/drug effects , Neuroprotective Agents/pharmacology , Peptide Fragments/pharmacology , Animals , Brain Injuries/pathology , Humans
15.
J Cancer Res Ther ; 14(Supplement): S779-S784, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30249903

ABSTRACT

CONTEXT: Methotrexate (MTX) is a cytotoxic chemotherapeutic element for various inflammatory diseases. The cytotoxic effect of MTX is also seen in normal tissues having a high proliferation rate including gastrointestinal and bone marrow. AIMS: The aim of this study was to find out whether oxidative damage could be relevant for MTX-induced toxicity in vivo using Wistar rats and to investigate the preventive potential of cactus cladodes. MATERIALS AND METHODS: Adult and healthy male Wistar rats (200-250 g) were pretreated by ethanol fraction of cactus cladodes. Following a single dose of MTX (20 mg/kg), either vehicle (saline) or ethanolic (400 mg/kg) was administered intraperitoneally. All animals were killed 24 h after the intraperitoneal injection of MTX. Small intestine samples were collected for malondialdehyde (MDA) level, protein carbonyl generation, and peroxidase and catalase (CAT) activity measurement. The small intestine was also collected for histopathology analysis. STATISTICAL ANALYSIS USED: Each experiment was conducted in triplicate separately. Values were presented as a mean ± standard deviation. Differences were considered significant at P < 0.05. RESULTS: Our results showed that MTX-induced significant alterations in oxidative stress markers noticed in the form of intestinal tissues damage, MDA level increased and protein carbonyls generation. CAT and peroxidase activities decreased with MTX administration. The combined treatment of MTX with cactus extracts showed a reduction of MTX-induced oxidative damage. CONCLUSIONS: It could be concluded that cactus cladodes extract was effective in protecting the small intestine against MTX-induced damage.


Subject(s)
Cactaceae/chemistry , Intestine, Small/drug effects , Methotrexate/toxicity , Plant Extracts/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Humans , Intestine, Small/injuries , Intestine, Small/pathology , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Protective Agents/chemistry , Protective Agents/pharmacology , Rats
16.
Sleep ; 41(10)2018 10 01.
Article in English | MEDLINE | ID: mdl-30016498

ABSTRACT

Amino acid transporters are involved in functions reportedly linked to the sleep/wake cycle: neurotransmitter synthesis and recycling, the regulation of synaptic strength, protein synthesis, and energy metabolism. In addition, the existence of bidirectional relationships among extracellular content, transport systems, and sleep/wake states is receiving emerging support. Nevertheless, the connection between amino acid transport and sleep/wake regulation remains elusive. To address this question, we used Drosophila melanogaster and investigated the role of LAT1 (large neutral amino acid transporter 1) transporters. We show that the two Drosophila LAT1-like transporters: Juvenile hormone Inducible-21 and minidiscs (Mnd) are required in dopaminergic neurons for sleep/wake regulation. Down-regulating either gene in dopaminergic neurons resulted in higher daily sleep and longer sleep bout duration during the night, suggesting a defect in dopaminergic transmission. Since LAT1 transporters can mediate in mammals the uptake of L-DOPA, a precursor of dopamine, we assessed amino acid transport efficiency by L-DOPA feeding. We find that downregulation of JhI-21, but not Mnd, reduced the sensitivity to L-DOPA as measured by sleep loss. JhI-21 downregulation also attenuated the sleep loss induced by continuous activation of dopaminergic neurons. Since LAT1 transporters are known to regulate target of rapamycin (TOR) signaling, we investigated the role of this amino acid sensing pathway in dopaminergic neurons. Consistently, we report that TOR activity in dopaminergic neurons modulates sleep/wake states. Altogether, this study provides evidence that LAT1-mediated amino acid transport in dopaminergic neurons is playing a significant role in sleep/wake regulation and is providing several entry points to elucidate the role of nutrients such as amino acids in sleep/wake regulation.


Subject(s)
Amino Acid Transport Systems/metabolism , Dopaminergic Neurons/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Sleep/physiology , Animals , Biological Transport , Dopamine/metabolism , Down-Regulation , Drosophila , Drosophila melanogaster/genetics , Female , Levodopa , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
17.
Neurotox Res ; 34(3): 559-573, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30006682

ABSTRACT

In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities. Chlorogenic acid (CGA) has been demonstrated to possess potent neuroprotective activities against oxidative stress in various cellular models and pathological conditions. Hence, CGA protect against oxidative stress and excitotoxic insults mediated by AMPA receptors and that the protective mechanisms involve free radical scavenging, Ca2+ handling in the cytosol, and modulating antioxidant enzyme system. CGA was associated with the protein kinase A (PKC) signaling pathways transduction. Caspases and calpains have been studied as apoptotic mediators and cell death in this model of AMPA toxicity. Inhibitors of caspases initiators, caspases 1, 8, and 9, the upstream of caspase 3 effectors, have totally abrogated the protective activity of CGA. Inhibitors of calpains also totally abrogated the protective activity of CGA. In addition, a potential role for the CGA in inhibiting Bax in oligodendrocyte cell model undergoing AMPA is inducing excitotoxic death. Our results indicate that CGA exhibits a protective potential via antioxidant and apoptosis caspases and calpains dependent against AMPA-mediated excitotoxicity, and these finding indicate that CGA is able to be a good candidate for preventive approach for neurodegenerative disorders associated with loss and damage in oligodendrocytes and AMPA-mediated excitotoxicity.


Subject(s)
Caspases/metabolism , Chlorogenic Acid/pharmacology , Oligodendroglia/drug effects , Optic Nerve/cytology , Protein Kinase C/metabolism , Signal Transduction/drug effects , Animals , Animals, Newborn , Cell Survival/drug effects , Cells, Cultured , Enzyme Inhibitors/pharmacology , Excitatory Amino Acid Agonists/toxicity , Hydrogen Peroxide/metabolism , Iron/metabolism , Mitochondria/drug effects , Rats , Rats, Sprague-Dawley , Rats, Wistar , Reactive Oxygen Species/metabolism , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/toxicity
18.
J Ethnopharmacol ; 224: 242-249, 2018 Oct 05.
Article in English | MEDLINE | ID: mdl-29870788

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Ficus carica fruit, a source of bioactive functional ingredients, have been traditionally long time used for its medicinal benefits as they improve the digestive system, treating constipation and used as a natural laxative. AIM OF THE STUDY: The recent study was investigated the ameliorative effect of Ficus carica L. aqueous extract (FCAE) on delayed gastric emptying and ulcerative colitis-improved motility disturbances in dextran sulfate sodium (DSS)-induced acute colitis in rats. MATERIALS AND METHODS: Wistar rats were assigned randomly and received 5% DSS for seven days. Ulcerative colitis diagnosis was confirmed by clinical signs, visible fecal blood and histopatological evaluation. The estimation of the action of colitis on TGI and constipation as well as the protective effect of extract, the intestinal biochemical and physiological parameters were measured using the charcoal meal test, loperamide (Lop)-induced constipation as well as spectrophotometric assays. FCAE (150 and 300 mg kg-1) was administered orally once per day for seven days 1 h after the loperamide treatment. Phenol-red colorimetric method was used to explore the action of FCAE on gastric emptying process. RESULTS: Ulcerative colitis caused a significantly gastrointestinal motility inhibition in normal rats and notably aggravated the constipation in LOP group. Oppositely, FCAE oral intake significantly increased levels of the gastrointestinal transit ratio and gastric emptying by accelerating of their times. Moreover, constipation severity induced by colitis was remarkably reduced in the FCAE treatment group, as demonstrated by a marked management of fecal parameters, water content, oxidative stress indicators, lipid metabolism, and intracellular mediators. Phytochemical analysis of FCAE revealed the presence of carbohydrates, polysaccharides, phenolic acids as gallic acid, chlorogenic acid, syringic acid and ellagic acid, and flavonoids (e.g. rutin, catechin, epicatechin and apeginine). CONCLUSIONS: The obtained results indicated that FCAE exhibits a natural laxative effect without provoking diarrhea and ameliorates functional gastrointestinal (GI) and motility disorders thus justifying its traditional usage.


Subject(s)
Colitis, Ulcerative/drug therapy , Ficus , Gastric Emptying/drug effects , Gastrointestinal Transit/drug effects , Laxatives/therapeutic use , Plant Extracts/therapeutic use , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/physiopathology , Dextran Sulfate , Fruit/chemistry , Laxatives/analysis , Laxatives/pharmacology , Male , Oxidative Stress/drug effects , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Phytotherapy , Plant Extracts/analysis , Plant Extracts/pharmacology , Rats, Wistar
19.
J Biomed Sci ; 25(1): 43, 2018 May 22.
Article in English | MEDLINE | ID: mdl-29788979

ABSTRACT

BACKGROUND: The Myristoylated Alanine-Rich C-kinase Substrate (MARCKS) and MARCKS-like protein 1 (MARCKSL1) have a wide range of functions, ranging from roles in embryonic development to adult brain plasticity and the inflammatory response. Recently, both proteins have also been identified as important players in regeneration. Upon phosphorylation by protein kinase C (PKC) or calcium-dependent calmodulin-binding, MARCKS and MARCKSL1 translocate from the membrane into the cytosol, modulating cytoskeletal actin dynamics and vesicular trafficking and activating various signal transduction pathways. As a consequence, the two proteins are involved in the regulation of cell migration, secretion, proliferation and differentiation in many different tissues. MAIN BODY: Throughout vertebrate development, MARCKS and MARCKSL1 are widely expressed in tissues derived from all germ layers, with particularly strong expression in the nervous system. They have been implicated in the regulation of gastrulation, myogenesis, brain development, and other developmental processes. Mice carrying loss of function mutations in either Marcks or Marcksl1 genes die shortly after birth due to multiple deficiencies including detrimental neural tube closure defects. In adult vertebrates, MARCKS and MARCKL1 continue to be important for multiple regenerative processes including peripheral nerve, appendage, and tail regeneration, making them promising targets for regenerative medicine. CONCLUSION: This review briefly summarizes the molecular interactions and cellular functions of MARCKS and MARCKSL1 proteins and outlines their vital roles in development and regeneration.


Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Myristoylated Alanine-Rich C Kinase Substrate/genetics , Vertebrates/physiology , Animals , Cell Movement , Intracellular Signaling Peptides and Proteins/metabolism , Myristoylated Alanine-Rich C Kinase Substrate/metabolism , Regeneration , Vertebrates/genetics , Vertebrates/growth & development
20.
Reprod Toxicol ; 78: 120-129, 2018 06.
Article in English | MEDLINE | ID: mdl-29673796

ABSTRACT

The success of pregnancy depends on the maternal immune system's ability to promote tolerance and host defense. This equilibrium is compromised in inflammatory and infectious impairment of placenta. Smoking during pregnancy exposes the fetus to severe complications which might result from an alteration in placenta macrophages (pMφ) functions. In this study, we assessed the effect of cigarette smoke extract (CSE) on the functions of third trimester pMφs.CSE inhibited particles uptake and the formation of multinucleated giant cells, a recently reported property of pMφs based on their ability to fuse in vitro. These alterations were associated with a CSE-induced abnormal activation of pMφs, which was characterized by an increased release of TNF, interleukin (IL)-33, and decreased IL-6 and IL-10 release. Furthermore, CSE enhanced the expression of metalloproteinase genes known to be involved in tissue remodeling. This effect of CSE on pMφs was specific because CSE affected circulating monocytes in a different way. Finally, we showed that nicotine affected in part the functional properties of pMφs. Taken together, these results showed that CSE modulated the functional activity of pMφs, which may compromise pregnancy.


Subject(s)
Macrophages/drug effects , Nicotiana , Placenta/cytology , Smoke/adverse effects , Tobacco Products , Bungarotoxins/pharmacology , Cytokines/metabolism , Female , Humans , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Nicotine/pharmacology , Phagocytosis/drug effects , Pregnancy , Pregnancy Trimester, Third
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