31 results on '"Fatma Tore"'
Search Results
2. The Potential Therapeutic Effects of Agmatine, Methylprednisolone, and Rapamycin on Experimental Spinal Cord Injury
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Tulin Firat, Aysel Kukner, Nilufer Ayturk, Ali Rıza Gezici, Erdinc Serin, Candan Ozogul, and Fatma Tore
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agmatine ,methylprednisolone ,rapamycin ,spinal cord injury ,Medicine ,Science - Abstract
Objective: In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic. Materials and Methods: In this animal-based experimental study, thirty adult male Sprague-Dawley rats were randomly divided into five groups as sham-control, injury, injury+MP, injury+rapamycin, injury+agmatine groups. SCI was induced by compressing the T7-8-9 segments of the spinal cord, using an aneurysm clip for one minute, and then rats were treated daily for 7 days. Seven days post-treatment, damaged spinal cord tissues of sacrificed rats were collected for microscopic and biochemical examinations using histopathologic and transmission electron microscope (TEM) scores. Malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were spectrophotometrically measured. Results: The results of this study showed that the damaged area was smaller in the rapamycin group when compared to the MP group. Many autophagic vacuoles and macrophages were observed in the rapamycin group. Degeneration of axon, myelin, and wide edema was observed in SCI by electron microscopic observations. Fragmented myelin lamellae and contracted axons were also noted. While MDA and GPx levels were increased in the injury group, MDA levels were significantly decreased in the agmatine and MP groups, and GPx levels were decreased in the rapamycin group. Conclusion: The results of our study confirmed that rapamycin and agmatine can be an effective treatment for secondary injury of SCI.
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- 2021
- Full Text
- View/download PDF
3. Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine
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Duygu Koyuncu Irmak, Erkan Kilinc, and Fatma Tore
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migraine ,neuroinflammation ,mast cells ,sensory neurons ,ATP ,CGRP ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Migraine is a primary headache disorder which has complex neurogenic pathophysiological mechanisms still requiring full elucidation. The sensory nerves and meningeal mast cell couplings in the migraine target tissue are very effective interfaces between the central nervous system and the immune system. These couplings fall into three categories: intimacy, cross-talk and a shared fate. Acting as the immediate call-center of the neuroimmune system, mast cells play fundamental roles in migraine pathophysiology. Considerable evidence shows that neuroinflammation in the meninges is the key element resulting in the sensitization of trigeminal nociceptors. The successive events such as neuropeptide release, vasodilation, plasma protein extravasation, and mast cell degranulation that form the basic characteristics of the inflammation are believed to occur in this persistent pain state. In this regard, mast cells and sensory neurons represent both the target and source of the neuropeptides that play autocrine, paracrine, and neuro-endocrine roles during this inflammatory process. This review intends to contribute to a better understanding of the meningeal mast cell and sensory neuron bi-directional interactions from molecular, cellular, functional points of view. Considering the fact that mast cells play a sine qua non role in expanding the opportunities for targeted new migraine therapies, it is of crucial importance to explore these multi-faceted interactions.
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- 2019
- Full Text
- View/download PDF
4. Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges
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Dilyara Nurkhametova, Igor Kudryavtsev, Valeriia Guselnikova, Maria Serebryakova, Raisa R. Giniatullina, Sara Wojciechowski, Fatma Tore, Albert Rizvanov, Jari Koistinaho, Tarja Malm, and Rashid Giniatullin
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mast cells ,ATP ,P2X7 receptor ,degranulation ,neuroinflammation ,migraine ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation. We show that ATP induced a time and dose-dependent activation of peritoneal mast cells as analyzed by the uptake of organic dye YO-PRO1 as well as 4,6-diamidino-2-phenylindole (DAPI). Both YO-PRO1 and DAPI uptake in mast cells was mediated by the P2X7 subtype of ATP receptors as demonstrated by the inhibitory effect of P2X7 antagonist A839977. Consistent with this, significant YO-PRO1 uptake was promoted by the P2X7 agonist 2′,3′-O-(benzoyl-4-benzoyl)-ATP (BzATP). Extracellular ATP-induced degranulation of native and cultured meningeal mast cells was shown with Toluidine Blue staining. Taken together, these data demonstrate the important contribution of P2X7 receptors to ATP-driven activation of mast cells, suggesting these purinergic mechanisms as potential triggers of neuroinflammation and pain sensitization in migraine.
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- 2019
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5. The preventive effect of low molecular weight heparin on CCL4-induced necrosis and apoptosis in rat liver
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Aysel Kukner, Fatma Tore, Tülin Firat, E. Hakan Terzi, Hakan Oner, Yasemin H Balaban, and Candan Ozogul
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Apoptosis ,Enoxaparin ,CCl4 ,Liver ,PCNA ,Specialties of internal medicine ,RC581-951 - Abstract
Introduction. Heparin having anti-inflammatory and anti-fibrotic properties may have therapeutic effect on liver injury. The present study investigated the effect of low molecular weight heparin (Enoxaparin) on carbon tetrachloride (CCl4) induced hepatic necrosis and apoptosis in rats.Material and methods. Thirty male rats were divided into 5 groups. Group I: Control; Group II: Olive oil dissolved CCl4 at dose of 1 mL/kg, ip, twice per week; Group III: CCl4 and Enoxaparin at dose of 180 lU/kg, sc, daily; Group IV: Enoxaparin; Group V: Olive oil at dose of 1 mL, ip, twice per week. The liver histology at the forth week was examined by haematoxylin-eosin, Masson’s trichrome, Toluidine blue and Periodic acid schiff stains. Proliferative and apoptotic activities were assessed semi-quantitatively by proliferating cell nuclear antigen (PCNA) and cas-pase-3 immune staining and TUNEL method. Semi-quantitative values formulated by the equation HSCORE = ΣP( including both distribution and intensity of staining. Additionally, nidogen and α-smooth muscle actin were labeled by immunohistochemistry.Results. CCl4 group had marked hepatocelluar necrosis around the vena centralis and increased inflammatory cells and mast cells. Hepatocytes showed deposition of lipid droplets, decrease in glycogen, apoptosis, and picnotic or enlarged nuclei. Enoxaparin reduced necrosis, apoptosis, and number of mast cells but had no effect on lipid droplets in hepatocytes. HSCORE’s of caspase-3 and PCNA were also significantly decreased by administration.Conclusion. Enoxaparin have beneficial effects against necrosis as well as apoptosis at the early stage of CCL4 induced liver injury.
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- 2010
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6. Mast cell activation ameliorates pentylenetetrazole‐induced seizures in rats: The potential role for serotonin
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Ibrahim Ethem Torun, Ayhan Cetinkaya, Erkan Kilinc, and Fatma Tore
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Male ,Serotonin ,medicine.medical_treatment ,Pharmacology ,Epileptogenesis ,Pathogenesis ,03 medical and health sciences ,Epilepsy ,0302 clinical medicine ,Immune system ,Seizures ,Cromolyn Sodium ,medicine ,Animals ,Mast Cells ,Rats, Wistar ,Saline ,Neuroinflammation ,030304 developmental biology ,0303 health sciences ,Chemistry ,General Neuroscience ,medicine.disease ,Rats ,Anticonvulsant ,Pentylenetetrazole ,Anticonvulsants ,030217 neurology & neurosurgery - Abstract
Neuroinflammation plays a key role in the pathogenesis of epilepsy, but the underlying mechanisms are not well understood. Mast cells are multifunctional immune cells that are also activated by stress. The effects of activated mast cells on epileptogenesis are not yet known. This study investigated the effects and mechanisms of compound 48/80-stimulated mast cell activation on pentylenetetrazole-induced epileptic seizures in rats. Male Wistar rats were separated into seven groups (n = 12). Group-1(NS+PTZ) received intraperitoneal saline solution, while groups 2(C-48/80+PTZ-1), 3(C-48/80+PTZ-2), and 4(C-48/80+PTZ-3) received compound-48/80 at doses of 0.5, 1, and 2 mg/kg, respectively, 30 min before 45 mg/kg pentylenetetrazole administration. Similarly, Group-5(Cr+C-48/80+PTZ) received 10 mg/kg cromolyn plus 2 mg/kg compound-48/80 before pentylenetetrazole, and Group-6(MC Dep+C-48/80+PTZ) was exposed to a mast cell-depletion process, and then received 2 mg/kg compound-48/80. Group-7(5-HT+PTZ) received 10 mg/kg serotonin. Seizure stages were evaluated using Racine's scale. Compound-48/80 at 2 mg/kg induced anticonvulsive effects against pentylenetetrazole-induced seizures by extending onset-times of both myoclonic-jerk and generalized tonic-clonic seizures (p = 0.0001), and by shortening the duration of generalized tonic-clonic seizure (p = 0.008). These effects were reversed by cromolyn (p = 0.0001). These effects were not observed in mast cell-depleted rats. Similarly to compound 48/80, serotonin also exhibited anticonvulsive effects against seizures (p < 0.05). Compound 48/80 acts as an anticonvulsant by activating mast cells in a dose-dependent manner. The anticonvulsive effects of mast cell activation may be mediated by serotonin. Mast cell activation may therefore provide protective activity against seizures under appropriate circumstances.
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- 2021
7. Thymoquinone Inhibits Neurogenic Inflammation Underlying Migraine Through Modulation of Calcitonin Gene-Related Peptide Release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in Rats
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Erkan Kilinc, Yasar Dagistan, Fatma Tore, Guler Bugdayci, and Tıp Fakültesi
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0301 basic medicine ,Male ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Immunology ,Phytochemicals ,Anti-Inflammatory Agents ,Pharmacology ,Calcitonin gene-related peptide ,03 medical and health sciences ,chemistry.chemical_compound ,Trigeminal ganglion ,Meningeal Mast Cells ,Nitroglycerin ,0302 clinical medicine ,Meninges ,In vivo ,Benzoquinones ,Immunology and Allergy ,Animals ,CGRP ,Mast Cells ,Thymoquinone ,Rats, Wistar ,Neuroinflammation ,Migraine ,Neurogenic inflammation ,Degranulation ,Rats ,Disease Models, Animal ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Neurogenic Inflammation ,Ex vivo - Abstract
Two main contributors of sterile neurogenic inflammation underlying migraine pain, calcitonin gene–related peptide (CGRP), and meningeal mast cells (MMCs) play a key role in the activation of the inflammatory cascade resulting in the sensitization of trigeminal nociceptors. It is well established that phytochemical agent thymoquinone exhibits multiple anti-inflammatory effects in different in vitro and in vivo models of neuroinflammation. But its effects on the CGRP release and meningeal mast cells are unknown. In the present study, we investigated the effects of thymoquinone on the CGRP release in migraine-related strategic structures which are crucial targets for anti-migraine drugs, and on the MMCs in glyceryl trinitrate (GTN)–induced in vivo migraine model as well as in the ex vivo meningeal preparations in rats. Anti-inflammatory thymoquinone ameliorated GTN-stimulated CGRP levels in plasma, and migraine-related structures including trigeminal ganglion and brainstem; moreover, thymoquinone inhibited degranulation of MMCs and prevented the increase in the number of MMCs in GTN-induced in vivo migraine model. However, in the ex vivo meningeal preparations, thymoquinone did not inhibit the GTN-induced CGRP release from trigeminal meningeal afferents. Our findings suggest that thymoquinone mediates modulation of CGRP release in trigeminal ganglion neurons and brainstem, and stabilization of MMCs. Thus, thymoquinone may be a promising candidate to prevent the meningeal neurogenic inflammation and consequently migraine.
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- 2019
8. Trimetazidine Increases Cell Survival and Inhibits the Activation of Inflammatory Response in Sodium Taurocholate–Induced Acute Pancreatitis
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Neriman Şengül, Tulin Firat, Açelya Aslan, Aysel Kükner, Sevil Isik, Recep Bayram, Taner Orug, Fatma Tore, Gulberk Ucar, Cemalettin Aydin, Ali Eba Demirbağ, Biruni Üniversitesi, Biyokimya, BAİBÜ, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Şengül, Neriman, Fırat, Tülin, Kükner, Aysel, and Bayram, Recep
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0301 basic medicine ,Sodium taurocholate ,Trimetazidine ,Mitochondrion ,Pharmacology ,medicine.disease_cause ,Experimental ,03 medical and health sciences ,Acute Pancreatitis ,0302 clinical medicine ,medicine ,Mast Cell ,Cell survival ,business.industry ,Therapeutic effect ,Mast cell ,medicine.disease ,Mitochondria ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,Acute pancreatitis ,030211 gastroenterology & hepatology ,Surgery ,business ,Oxidative stress ,medicine.drug - Abstract
Objective: To evaluate the therapeutic effects of trimetazidine (TMZ) in an experimental acute pancreatitis (AP) model induced with sodium taurocholate (STC). Summary of Background Data: At present, AP is considered a disease with no specific treatment. Preventing mitochondrial dysfunction in acinar cells may be an option for specific treatment of AP. TMZ is an anti-ischemic drug with anti-inflammatory, antioxidant, and mitochondrial modulatory effects. Methods: Rats were divided into 4 groups. AP was induced in the AP (n = 7) and AP + TMZ (n = 7) groups by an injection of 4% sodium taurocholate to the pancreatic duct. The sham (n = 6) and drug (n = 6) groups were designated as control groups. The AP + TMZ and drug groups were administered TMZ. Samples were taken at 72 hours, and histopathologic changes as well as biochemical parameters were analyzed. Results: Serum amylase, tissue myeloperoxidase activity, malondialdehyde levels, serum cytokine levels, and mast cell degranulation rates were elevated after induction of AP, whereas tissue antioxidant enzyme activities and cell viability rates [determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay] decreased. These parameters were found to be different in the AP group compared with those in all other groups (P < 0.05). A significant improvement of all parameters was achieved with the TMZ treatment of AP. Histologically, significant differences were found between the AP and AP + TMZ groups in terms of leukocyte infiltration, necrosis, and apoptotic cell counts. Conclusions: In this study, we demonstrated that TMZ treatment protected the mitochondrial function and prevented the activation of the inflammatory cascade in the sodium taurocholate–induced AP model.
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- 2017
9. Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain
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Cindy Guerrero-Toro, Liliana L. Luz, Arina Timonina, Ksenia Koroleva, Rashid Giniatullin, Carmela Vitale, Irina V. Shelukhina, Boris V. Safronov, Fatma Tore, Andrey Zakharov, Raisa Giniatullina, Erkan Kilinc, Max Gubert-Olive, Instituto de Investigação e Inovação em Saúde, and Biruni Üniversitesi
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Male ,Nociception ,0301 basic medicine ,Agonist ,Serotonin ,Patch-Clamp Techniques ,Cations, Divalent ,medicine.drug_class ,Calcitonin Gene-Related Peptide ,Migraine Disorders ,Trigeminal nerve ,5-HT3 Receptor ,Action Potentials ,TRPV Cation Channels ,Spike ,Serotonergic ,Tissue Culture Techniques ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Meninges ,Serotonin Agents ,0302 clinical medicine ,medicine ,Animals ,Neurons, Afferent ,Trigeminal Nerve ,Rats, Wistar ,Migraine ,Pharmacology ,Chemistry ,Voltage-Sensitive Dye Imaging ,Sumatriptan ,5-HT3 receptor ,030104 developmental biology ,Receptors, Serotonin ,Excitatory postsynaptic potential ,Calcium ,Female ,Brainstem ,Neuroscience ,030217 neurology & neurosurgery ,Histamine ,medicine.drug - Abstract
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The study was supported by the Finnish Academy (grant 277442). AZ was supported by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities and the Government of the Russian Federation (grant No.11.G34.31.0075). The work of IS was supported by RFBR grant 14-04-00885. BVS was supported by the grant from the Fundacao para a Ciencia e a Tecnologia (PTDC/NEU-NMC/1259/2014) and from the programme NORTE 2020., Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms. The 5-HT3-receptor antagonist MDL-72222 or 5-HT1BID-receptor antagonist GR127935 largely reduced, but their combination completely prevented the excitatory pro-nociceptive action of 5-HT. The 5-HT3 agonist mCPBG activated spikes in MDL-72222-dependent manner but the 5HT-1 receptor agonist sumatriptan did not affect the nociceptive firing. 5-HT also triggered peripheral CGRP release in meninges, which was blocked by MDL-72222.5-HT evoked fast membrane currents and Ca2+ transients in a fraction of trigeminal neurons. Immunohistochemistry showed expression of 5-HT3A receptors in fibers innervating meninges. Endogenous release of 5-HT from degranulated mast cells increased nociceptive firing. Low pH but not histamine strongly activated firing. 5-HT reduced monosynaptic inputs from trigeminal A delta- and C-afferents to the upper cervical lamina I neurons and this effect was blocked by MDL-72222. Consistent with central inhibitory effect, 5 HT reduced CGRP release in the brainstem slices. In conclusion, 5-HT evokes powerful pro-nociceptive peripheral and anti-nociceptive central effects in trigeminal system transmitting migraine pain. (C) 2016 Elsevier Ltd. All rights reserved., Finnish Academy [277442]; Government of the Russian Federation [11.G34.31.0075]; RFBR [14-04-00885]; Fundacao para a Ciencia e a Tecnologia [PTDC/NEU-NMC/1259/2014]; programme NORTE
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- 2017
10. Shared fate of meningeal mast cells and sensory neurons in migraine
- Author
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Fatma Tore, Duygu Koyuncu Irmak, Erkan Kilinc, and Biruni Üniversitesi
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0301 basic medicine ,Inflammation ,Review ,Calcitonin gene-related peptide ,PACAP ,Autonomic Nervous System ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Neuroinflammation ,Neuroimmune system ,medicine ,Mast Cells ,CGRP ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Migraine ,business.industry ,Degranulation ,Mast cell ,Sensory neuron ,ATP ,030104 developmental biology ,medicine.anatomical_structure ,Sensory Neurons ,medicine.symptom ,business ,Neuroscience ,030217 neurology & neurosurgery ,Sensory nerve - Abstract
Migraine is a primary headache disorder which has complex neurogenic pathophysiological mechanisms still requiring full elucidation. The sensory nerves and meningeal mast cell couplings in the migraine target tissue are very effective interfaces between the central nervous system and the immune system. These couplings fall into three categories: intimacy, cross-talk and a shared fate. Acting as the immediate call-center of the neuroimmune system, mast cells play fundamental roles in migraine pathophysiology. Considerable evidence shows that neuroinflammation in the meninges is the key element resulting in the sensitization of trigeminal nociceptors. The successive events such as neuropeptide release, vasodilation, plasma protein extravasation, and mast cell degranulation that form the basic characteristics of the inflammation are believed to occur in this persistent pain state. In this regard, mast cells and sensory neurons represent both the target and source of the neuropeptides that play autocrine, paracrine, and neuro-endocrine roles during this inflammatory process. This review intends to contribute to a better understanding of the meningeal mast cell and sensory neuron bi-directional interactions from molecular, cellular, functional points of view. Considering the fact that mast cells play a sine qua non role in expanding the opportunities for targeted new migraine therapies, it is of crucial importance to explore these multi-faceted interactions.
- Published
- 2019
11. The Comparison of Effects of Applications of Compound 48/80 and Mast Cell Mediator Suspension on Inflammation in Rats: A Methodological Study for Acute Inflammatory Pain
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Ayhan Cetinkaya, Erkan Kilinc, Yasar Dagistan, Fatma Tore, BAİBÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Kılınç, Erkan, and Biruni Üniversitesi
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0301 basic medicine ,Compound-48/80 ,medicine.medical_treatment ,Substance P ,Inflammation ,Pharmacology ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Health Care Sciences and Services ,Inflammatory Pain ,Medicine ,Sağlık Bilimleri ve Hizmetleri ,Saline ,business.industry ,Degranulation ,[No Keywords] ,General Medicine ,Compound 48/80 ,Mast cell ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Substance-P ,Inflammatory pain,mast cell degranulation,substance-P,compound-48/80 ,Analysis of variance ,medicine.symptom ,business ,Mast Cell Degranulation ,030217 neurology & neurosurgery - Abstract
Objective: Inflammation underlies the pathological basis of most diseases. Substance-P is a key mediator that participates in various inflammatory processes and painful conditions. Mast cells (MCs) have a key role in inflammatory processes via mediators released from their granules. The experimental models for the investigation of pathogenesis and treatment of inflammatory diseases represent merely certain characteristics of inflammatory cases, therefore, more comprehensive models are required. We aimed to compare effects of administrations of the compound-48/80 and mast cell mediator suspension (MCMS) obtained from peritoneal MCs on the inflammation in rats.Methods: Rats were divided into five groups (n=6): Intraperitoneally, Control group received 0.2 ml saline; C-48/80 group received 2 mg/kg compound-48/80; MCMS group received 0.2 ml MCMS; Cr+C-48/80 group received 10 mg/kg cromolyn plus compound-48/80; Cr+MCMS group received cromolyn plus MCMS. Potent inflammatory markers, plasma substance-P levels, and number and degranulation of dural MCs were measured. Data were analyzed using one-way ANOVA followed by Dunnett’s post hoc test.Results: Compound-48/80 increased plasma substance-P levels (p
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- 2019
12. Mast Cell Degranulation Mediates Compound 48/80-Induced Meningeal Vasodilatation Underlying Migraine Pain
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Fatma Tore, Erkan Kilinc, Yasar Dagistan, 0-Belirlenecek, and Biruni Üniversitesi
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Pathology ,medicine.medical_specialty ,Dura mater ,Middle meningeal artery ,Migraine,meningeal artery,dural mast cell,neurogenic inflammation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Interstitial fluid ,medicine.artery ,medicine ,Migraine ,Dural Mast Cell ,Neurogenic inflammation ,business.industry ,Degranulation ,[No Keywords] ,030206 dentistry ,General Medicine ,Compound 48/80 ,medicine.disease ,Mast cell ,Migren ,Meningeal Artery ,medicine.anatomical_structure ,chemistry ,Anesthesia ,Neurogenic Inflammation ,business ,030217 neurology & neurosurgery - Abstract
Objective: The cranial dura mater contains plenty of mast cells and is principally supplied by the middle meningeal artery which has a key role in the generation of headaches. Neurogenic inflammation caused by perivascular nerve activation and dural vasodilation is held responsible for migraine pain. Dural mast cells contribute neurogenic inflammation and migraine via vasoactive and proinflammatory mediators in their secretory granules. In the present study, it was aimed to investigate vasoactive effect of mast cell degranulating agent compound 48/80 induced dural mast cell degranulation on the middle meningeal artery and its anterior and posterior branches. Methods: Isolated skulls obtained from male Wistar rats were divided into 2 halves. The skull cavities with intact the dura mater were applied synthetic interstitial fluid for control group or mast cell degranulating agent compound 48/80 (10 mu g/ml) in synthetic interstitial fluid for treated group at 37 degrees C for 15 min. Diameters of middle meningeal artery and its anterior and posterior branches were measured and mast cells were counted from whole-mount preparations of meningeal dura mater. Results: While compound 48/80 induced massive degranulation of dural mast cells (P, Amaç: Kraniyal dura mater çok sayıda mast hücresi barındırmaktadır ve başlıca baş ağrılarının oluşumunda önemli bir role sahip olan middle meningeal arter tarafından beslenmektedir. Migren baş ağrısı oluşumunda, perivasküler sinir aktivasyonu ve dural vazodilatasyonun yol açtığı nörojenik enflamasyon sorumlu tutulmaktadır. Dural mast hücreleri sekretuar granüllerinde bulunan vazoaktif ve proinflamatuar mediyatörler aracılığıyla nörojenik enflamasyon ve migrene katkıda bulunmaktadır. Sunulan çalışmada bir mast hücre degranülatörü olan compound-48/80 ile oluşturulan dural mast hücre degranülasyonunun middle meningeal arter ve bunun anterior ve posterior dalları üzerine vazoaktif etkisinin araştırılması amaçlanmıştır. Yöntemler: Wistar erkek sıçanlardan elde edilen izole kranyumlar iki yarıya bölündü. Dura materi sağlam hemi-kranyumların boşluğuna kontrol grubu için 37 oC’ de yapay interstisyel sıvı ve çalışma grubu için bir mast hücre degranüle edici madde olan compound-48/80 (10 µg/ml) 15 dakika uygulandı. Middle meningeal arter ve bunun anterior ve posterior dallarının çapları ölçüldü ve meningeal dura mater preparasyonlarından mast hücreleri sayıldı. Bulgular: Compound-48/80 dural mast hücrelerinin kitlesel degranülasyonunu tetiklerken (P
- Published
- 2018
13. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats
- Author
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Aysel Kükner, Fatma Tore, Yasar Dagistan, Gizem Söyler, Sami Agus, Erkan Kilinc, Bayram Yilmaz, Biruni Üniversitesi, Kilinc, E., Dagistan, Y., Kukner, A., Yılmaz, B., Agus, S., Soyler, G., Tore, F., and Yeditepe Üniversitesi
- Subjects
Calcitonin ,Male ,0301 basic medicine ,c-fos ,Physiology ,Migraine Disorders ,Calcitonin Gene-Related Peptide ,Pain ,mast cells ,Pharmacology ,Calcitonin gene-related peptide ,calcitonin gene-related peptide ,Cell Degranulation ,03 medical and health sciences ,Trigeminal ganglion ,0302 clinical medicine ,Meninges ,salmon calcitonin ,In vivo ,meninges ,Physiology (medical) ,medicine ,Animals ,migraine ,Mast Cells ,Rats, Wistar ,Migraine ,business.industry ,Degranulation ,Mast cell ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Nociception ,Gene Expression Regulation ,Trigeminal Ganglion ,cardiovascular system ,Salmon Calcitonin ,Dura Mater ,business ,Proto-Oncogene Proteins c-fos ,030217 neurology & neurosurgery ,Ex vivo ,circulatory and respiratory physiology - Abstract
This work was supported by Abant Izzet Baysal University Scientific Research Fund [Grant number: 2016.08.02.1060]., The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10mg/kg), vehicle, saline+GTN, SC (50g/kg)+GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100mol/L GTN, 50mol/L SC, and SC+GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief., Abant Izzet Baysal University Scientific Research Fund [2016.08.02.1060]
- Published
- 2018
14. Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats
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Fatma Tore, Erkan Kilinc, Aysu Kiyan, Tulin Firat, Aysel Kükner, and Neşe Tunçel
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Neurogenic inflammation ,integumentary system ,business.industry ,medicine.medical_treatment ,Dura mater ,Vasoactive intestinal peptide ,Neuropeptide ,Anatomy ,musculoskeletal system ,Mast cell ,Ganglion ,Cellular and Molecular Neuroscience ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Sympathectomy ,Internal medicine ,Medicine ,Ganglionectomy ,business - Abstract
Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c-Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague-Dawley male rats with body weights of 200–250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c-Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P
- Published
- 2014
15. The effect of kisspeptin on spermatogenesis and apoptosis in rats
- Author
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Aysel Kükner, Fatma Tore, Candan Ozogul, Bayram Yilmaz, İsmail Engin Kandirali, Tulin Firat, Nilüfer Aytürk, İstanbul Medipol Üniversitesi, Aytürk, Nilüfer, Fırat, Tülin, Kükner, Aysel, Özoğul, Candan, Töre, Fatma, Kandıralı, İsmail Engin, Yılmaz, Bayram, and Yeditepe Üniversitesi
- Subjects
Male ,0301 basic medicine ,endocrine system ,Kisspeptin ,endocrine system diseases ,medicine.drug_class ,Apoptosis ,030209 endocrinology & metabolism ,urologic and male genital diseases ,Andrology ,Masson's trichrome stain ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Rats, Wistar ,Spermatogenesis ,Cells, Cultured ,Testosterone ,Cerrahi ,Kisspeptins ,Spermatogenic Cell ,TUNEL assay ,Leydig cell ,urogenital system ,business.industry ,Leydig Cells ,General Medicine ,Kisspeptin,spermatogenesis,apoptosis,Leydig cells ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Vacuolization ,Gonadotropin ,business ,human activities ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background/aim: To study the effect of kisspeptin, a gonadotropin release stimulator, on the testicular tissue of the rat. Materials and methods: Four groups were formed as follows: control, Kiss-10 50nmol administration for 1 day, Kiss-10 administration for 13 days, and one last group kept for 7 days following Kiss-10 applied for 13 days. Testicular tissues were stained with hematoxylineosin, periodic acid Schiff, Masson trichrome staining, terminal deoxynucleotidyl transferased UTP nick-end labeling, and Ki-67 immune staining. Serum testosterone levels were determined. Results: Serum testosterone level increased following acute application, while it was reduced by chronic treatment. Spermatogenic cells as stained by Ki-67 and TUNEL increased in the treated groups compared to the controls. Following a 7-day rest after treatment, a decrease in testosterone levels and Ki-67–stained cell numbers and an increase in TUNEL-stained cells were observed. Leydig cells showed increased vacuolization in the Kiss-1 group. Leydig cell vacuolization continued in the Kiss (13) group and was reduced in the Kiss (13 + 7) group. Conclusion: Kiss-10 increased spermatogenic cell proliferation, while testosterone level and proliferation decreased and apoptosis increased during the waiting period. Background/aim: To study the effect of kisspeptin, a gonadotropin release stimulator, on the testicular tissue of the rat. Materials and methods: Four groups were formed as follows: control, Kiss-10 50nmol administration for 1 day, Kiss-10 administration for 13 days, and one last group kept for 7 days following Kiss-10 applied for 13 days. Testicular tissues were stained with hematoxylineosin, periodic acid Schiff, Masson trichrome staining, terminal deoxynucleotidyl transferased UTP nick-end labeling, and Ki-67 immune staining. Serum testosterone levels were determined. Results: Serum testosterone level increased following acute application, while it was reduced by chronic treatment. Spermatogenic cells as stained by Ki-67 and TUNEL increased in the treated groups compared to the controls. Following a 7-day rest after treatment, a decrease in testosterone levels and Ki-67–stained cell numbers and an increase in TUNEL-stained cells were observed. Leydig cells showed increased vacuolization in the Kiss-1 group. Leydig cell vacuolization continued in the Kiss (13) group and was reduced in the Kiss (13 + 7) group. Conclusion: Kiss-10 increased spermatogenic cell proliferation, while testosterone level and proliferation decreased and apoptosis increased during the waiting period.
- Published
- 2017
16. The Effect of Experimental Liver Injury on Lung and Role of Mast Cells
- Author
-
Tulin Firat, Nilufer Ulas, Aysel Kükner, E. Hakan Terzi, and Fatma Tore
- Subjects
Liver injury ,Pathology ,medicine.medical_specialty ,Lung ,General Medicine ,Lung injury ,Biology ,medicine.disease ,Mast cell ,medicine.anatomical_structure ,Edema ,Parenchyma ,medicine ,medicine.symptom ,Ligation ,Hepatopulmonary syndrome - Abstract
Objective: To examine lung tissue and the number of mast cells related to experimen - tal liver injury under the light microscope. Material and Methods: Adult male Wistar albino rats were used and they were divided into 3 groups with randomly dividing 6 animals in each group. The groups were control, CCL4 and ligation groups. CCl4 (1 ml/kg body weight, intraperitoneal) was administered twice per week, for 8 weeks. In ligation group, common bile duct was ligated with for 3 weeks. Liver and lung tissue samples were taken and stained with hematoxylin-eosin. Lung sections were stained with toluidine blue and parenchymal and pleural mast cells were counted. Re- sults: In ligation and CCl4 groups; interalveolar septal thickening, capillary congestion, edema, in - creased inflammatory cells and degranulated mast cells were observed in the lung tissues. In the ligation group, these changes were more pronounced than CCl4 group. Parenchymal and pleural mast cell numbers were significantly increased in the ligation and CCl4 groups when compared to the control group. Conclusion: Increased mast cell numbers could mediate lung injury induced by liver injury, which called as hepatopulmonary syndrome.
- Published
- 2013
17. Anatomical and Functional Relationships Between Sensory Nerves and Mast Cells
- Author
-
Fatma Tore and Nese Tuncel
- Subjects
Pharmacology ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,Sensory system ,General Medicine ,Mast (botany) ,business ,Neuroscience - Published
- 2011
18. The preventive effect of low molecular weight heparin on CCL4-induced necrosis and apoptosis in rat liver
- Author
-
Candan Ozogul, Yasemin H. Balaban, E. Hakan Terzi, Fatma Tore, Hakan Öner, Aysel Kükner, Tulin Firat, BAİBÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Kükner, Aysel, Töre, Fatma, and İç Hastalıkları
- Subjects
CCl4 ,medicine.medical_specialty ,Necrosis ,Specialties of internal medicine ,CCL4 ,Apoptosis ,chemistry.chemical_compound ,Internal medicine ,Lipid droplet ,medicine ,PCNA ,Enoxaparin ,Liver injury ,Gastroenterology & Hepatology ,Hepatology ,business.industry ,General Medicine ,Heparin ,medicine.disease ,Staining ,Endocrinology ,chemistry ,Liver ,RC581-951 ,Immunology ,Carbon tetrachloride ,medicine.symptom ,business ,medicine.drug - Abstract
WOS:000285909200009 PubMed: 21057164 Introduction Heparin having anti inflammatory and anti fibrotic properties may have therapeutic effect on liver injury The present study investigated the effect of low molecular weight heparin (Enoxaparin) on carbon tetrachloride (CCl4) induced hepatic necrosis and apoptosis in rats Material and methods Thirty male rats were divided into 5 groups Group I Control, Group II Olive oil dissolved CCl4 at dose of 1 mL/kg, ip, twice per week, Group III CCl4 and Enoxaparin at dose of 180 IU/kg, sc, daily, Group IV Enoxaparin, Group V Olive oil at dose of 1 mL, ip, twice per week The liver histology at the forth week was examined by haematoxylin eosin, Masson's trichrome, Toluidine blue and Periodic acid schiff stains Proliferative and apoptotic activities were assessed semi quantitatively by proliferating cell nuclear antigen (PCNA) and cas pase 3 immune staining and TUNEL method Semi quantitative values formulated by the equation HSCORE = Sigma P-i (1+1) including both distribution and intensity of staining Additionally, mdogen and a smooth muscle actin were labeled by immunohistochemistry Results CCl4 group had marked hepatocelluar necrosis around the vena centralis and increased inflammatory cells and mast cells Hepatocytes showed deposition of lipid droplets, decrease in glycogen, apoptosis, and picnotic or enlarged nuclei Enoxaparin reduced necrosis, apoptosis, and number of mast cells but had no effect on lipid droplets in hepatocytes HSCORE's of caspase 3 and PCNA were also significantly decreased by administration Conclusion Enoxaparin have beneficial effects against necrosis as well as apoptosis at the early stage of CCL4 induced liver injury
- Published
- 2010
19. The Effects of Vasoactive Intestinal Peptide on Dura Mater Nitric Oxide Levels and Vessel-Contraction Responses in Sympathectomized Rats
- Author
-
Dilek Dogrukol-Ak, Orhan Tansel Korkmaz, Neşe Tunçel, Fatma Tore, Anadolu Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, and Ak, Dilek
- Subjects
Male ,medicine.medical_specialty ,Migraine Disorders ,Dura mater ,medicine.medical_treatment ,Vasoactive intestinal peptide ,Neuropeptide ,Superior Cervical Ganglion ,Nitric Oxide ,Nitric oxide ,Rats, Sprague-Dawley ,Norepinephrine ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Humans ,Sympathectomy ,Migraine ,Neurogenic inflammation ,business.industry ,General Medicine ,Rats ,Ganglion ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Vasoconstriction ,Anesthesia ,Nociceptor ,Dura Mater ,business ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
WOS: 000276882800008, PubMed ID: 19936638, Nitric oxide (NO) and neurogenic inflammation in dura mater due to nociceptor activation has been implicated for pathophysiology of primary headache disorders. Development of migraine has also been observed in patients treated with ganglion blockage for sympathetic reflex dystrophy. Vasoactive intestinal peptide (VIP) is an antioxidant, anti-inflammatory, and neuroprotective neuropeptide. This study is intended to investigate the effects of VIP on dura mater NO levels and vessel-contraction responses in sympathectomized rats. In the experiments, 30 male rats in five groups were used. Group 1 sympathectomized: under anesthesia, superior cervical sympathetic ganglion was removed via incision at the center line in the neck area. Group 2 sympathectomized + VIP: postoperative VIP of 25 ng/kg/day (0.2 ml) intraperitoneally administered to the rats exposed to the same operations for 5 days. Group 3 sham: ganglia and nerves were exposed but not dissected. Group 4 control: no treatment was done. Group 5 VIP: only VIP was administered for 5 days. Sympathectomy induced a significant increase in dura mater NO levels and VIP decreased NO to control levels and increased the norepinephrine vessel-contraction responses of sympathectomized rats. VIP is an efficient NO modulator in superior cervical ganglionectomized rats.
- Published
- 2009
20. Mast Cells: Target and Source of Neuropeptides
- Author
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Fatma Tore and Neşe Tunçel
- Subjects
Pharmacology ,Cell signaling ,Neuropeptides ,Degranulation ,Receptors, Cell Surface ,Enteroendocrine cell ,Inflammation ,Biology ,Mast cell ,Cell biology ,Interleukin 33 ,Paracrine signalling ,Immune system ,medicine.anatomical_structure ,Drug Discovery ,Immunology ,medicine ,Animals ,Humans ,Mast Cells ,medicine.symptom - Abstract
Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens. Mast cells secrete mediators, go under total degranulation, or degranulate only some of the specific granules with required content according to the environmental conditions, pathogens or signaling molecules binding to their receptors. Mast cells are functionally multi faceted cells. A single cell can behave such as an immune cell, an endocrine cell and even as a sensorial neuron. In this context, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. Specifically the mast cells proximal to nerve fibers, contain, secrete and respond to, several neuropeptides, suggesting many potential functions for mast cells in health and disease. Mast cells are target cells for neuropeptides and, they have distinct profiles of responsiveness to these molecules. This extends the flexibility of neurogenic signaling pathways via reciprocity. Those neuropeptides have direct and indirect effects on mast cells such as inducing or suppression of degranulation, triggering, modulation or amplification of mediator content and release. The exploration of interactions of mast cells and neurons is a promising field of study which may bring treatments to several diseases. Since mast cells seem to form the major link between neurons and inflammation via neuropeptides, mast cell and mast cell mediator connection may lead to a better understanding of the autocrine, paracrine, and neuro-immune-endocrine systems in physiology and physiopathology. Therefore, mast cell manipulator drug designs, capable of granular content modulation, with effects on, selective mediator release, activity and, ablation of mast cells, would be very beneficial for the treatment of various diseases that mast cells may be involved in.
- Published
- 2009
21. From Adipose Tissue Protein Secretion to Adipopharmacology of Disease
- Author
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Pepa Atanassova, Luigi Aloe, George N. Chaldakov, Fatma Tore, Neşe Tunçel, Marco Fiore, and Anton B. Tonchev
- Subjects
Pharmacology ,medicine.medical_specialty ,Adiponectin ,Endocrinology, Diabetes and Metabolism ,Glucose transporter ,Adipokine ,Adipose tissue ,Biology ,medicine.disease ,Endocrinology ,Insulin resistance ,Nerve growth factor ,Internal medicine ,medicine ,biology.protein ,Immunology and Allergy ,Secretory pathway ,GLUT4 - Abstract
An extensive research in the last few years has identified about hundred adipose tissue-secreted proteins, named adipokines or adipocytokines. However, our knowledge of the structures and molecules involved in the intracellu- lar secretory pathway (synthesis, translocation, folding, targeting, sorting, storage, and exocytosis) of adipokines is at pre- sent limited. Relatively more is known about insulin-responsive trafficking of glucose transporters (GLUTs). Adipokines have multiple biological functions beyond lipid and carbohydrate metabolism, whereas GLUT4 is the major glucose transporter of adipocytes and skeletal muscles. Adipokines play an important role in the pathogenesis of a wide variety of diseases, and dysregulation of GLUT4 transport is implicated in insulin resistance and related disorders. Conceptually, adipobiology of disease has emerged as a novel field of studies in basic and clinical medicine. Here we present a state-of- the-science on some aspects of these studies with a special reference to the intracellular secretory pathway, focusing on adiponectin, GLUT4, and nerve growth factor (NGF), and suggesting that each step of this pathway may be a potential drug target. Given the beneficial effects of adiponectin, NGF and GLUT4 on various metabolic, vascular and inflamma- tory processes, a hypothesis of metabotrophic factor deficit in the pathogenesis of adipose-linked diseases is discussed. Adipopharmacological evaluation of this hypothesis may provide novel targets for drug development. W e respectfully ded ic ate th is rev ie w t o Professor Rita Lev i- M ontalc in i on oc cas ion of her 97 th birthday (born 22 April, 1909) cellular secretory pathways. We propose that, at a mechanis- tic level, each step of these pathways may provide a novel target for drug development against adipose tissue-linked diseases. Given the beneficial effects of adiponectin, NGF and GLUT4 on various metabolic, vascular and inflamma- tory processes, a hypothesis of metabotrophic factor deficit in the pathogenesis of these diseases is discussed.
- Published
- 2007
22. Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats
- Author
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Erkan, Kilinc, Tülin, Firat, Fatma, Tore, Aysu, Kiyan, Aysel, Kukner, and Nese, Tunçel
- Subjects
Male ,Rats, Sprague-Dawley ,Oncogene Proteins v-fos ,Animals ,Dura Mater ,Mast Cells ,Sympathectomy ,Trigeminal Nuclei ,Statistics, Nonparametric ,Rats ,Vasoactive Intestinal Peptide - Abstract
Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c-Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague-Dawley male rats with body weights of 200-250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c-Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P 0.001). VIP decreased the number of mast cells in both sides of the dura mater in sympathectomized rats. VIP also decreased c-Fos expression in the ipsilateral trigeminal nucleus of sympathectomized rats (P 0.001). In the context of an experimental superior cervical ganglionectomy model of migraine, VIP is an efficient modulator of neurogenic inflammation of the dura.
- Published
- 2014
23. Effects of sepsis on mast cells in rat dura mater: influence of<scp>L</scp>-NAME and VIP
- Author
-
P. Aubineau, Fatma Tore, Neşe Tunçel, A. M. Reynier-Rebuffel, and J Callebert
- Subjects
Pharmacology ,medicine.medical_specialty ,Dura mater ,Vasoactive intestinal peptide ,Chymase ,Connective tissue ,Heparin ,Biology ,Mast cell ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,medicine ,Serotonin ,Histamine ,medicine.drug - Abstract
1. The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. 2. Three different populations of mast cells were identified in control rats: connective tissue type mast cells (CTMC) which contain rat mast cell protease1 (RMCP1), histamine, serotonin and heparin, mucosal type mast cells (MMC) which contain RMCP2, histamine and serotonin, and intermediate type which contains both RMCP1 and RMCP2 and probably various proportions of amines and heparin. 3. LPS (25 mg kg(-1) i.p.) caused changes in the proportions of the various types of mast cells. The number of MMC and intermediate type mast cells significantly increased and the number of mast cells immunopositive for both heparin and serotonin significantly decreased. Biochemical analysis showed that the histamine concentration of dura increased while its serotonin concentration decreased. 4. While vasoactive intestinal peptide (VIP) (25 ng kg(-1) i.p.) appears to potentiate LPS effects on dura mater mast cells, non-selective inhibition of nitric oxide (NO) synthase by N(g)-nitro-L-arginine methyl ester (L-NAME) (30 mg kg(-1) i.p.) did not influence sepsis-induced mast cell changes. 5. These findings suggest that mast cells of dura mater may play a role in brain protection during sepsis.
- Published
- 2001
24. Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock
- Author
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Varol Sahinturk, Dilek Ak, Muzaffer Tunçel, Fatma Tore, Neşe Tunçel, Anadolu Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, Ak, Dilek, and Tunçel, Muzaffer
- Subjects
Male ,Physiology ,Vasoactive intestinal peptide ,Kidney ,medicine.disease_cause ,Biochemistry ,Antioxidants ,Cell Degranulation ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,Endocrinology ,1- Methylhistamine ,Mast Cells ,Chemistry ,Methylhistamines ,Degranulation ,Catalase ,Mast cell ,Shock, Septic ,NG-Nitroarginine Methyl Ester ,medicine.anatomical_structure ,Liver ,Shock (circulatory) ,Female ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,Histamine ,Vasoactive Intestinal Peptide ,Antioxidant Enzymes ,medicine.medical_specialty ,Nitric Oxide ,Sepsis ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Animals ,Superoxide Dismutase ,Septic shock ,medicine.disease ,Rats ,Vip ,Oxidative Stress ,Endotoxic Shock ,Rat ,Lipid Peroxidation ,Oxidative stress - Abstract
PubMed: 10704723, Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit. The present study showed that endotoxic shock did not lead to oxidative stress in either liver or kidney of the rats. On the other hand, mast cells, based on their location, displayed functional heterogeneity to the septic insults. VIP possibly modulated the specific reactions of the tissues to mediators released from mast cells during septic shock. The most prominent effect of VIP as compared to nitric oxide synthesis inhibition was related to mast cells. In conclusion, the prevention of mast cell reactivity by VIP could be a potential therapeutic strategy in controlling septic shock, This work was supported by the grant from Research Fund of Osmangazi University.
- Published
- 2000
25. The Effect of Vasoactive Intestinal Peptide (VIP) and Inhibition of Nitric Oxide Synthase on Survival Rate in Rats Exposed to Endotoxin Shock
- Author
-
Fatma Tore and Neşe Tunçel
- Subjects
Lipopolysaccharides ,Male ,Analysis of Variance ,Time Factors ,biology ,Chemistry ,General Neuroscience ,Vasoactive intestinal peptide ,Blood Pressure ,Pharmacology ,Shock, Septic ,General Biochemistry, Genetics and Molecular Biology ,Rats ,Endotoxin shock ,Rats, Sprague-Dawley ,Nitric oxide synthase ,NG-Nitroarginine Methyl Ester ,History and Philosophy of Science ,Escherichia coli ,biology.protein ,Animals ,Female ,Nitric Oxide Synthase ,Survival rate ,Vasoactive Intestinal Peptide - Published
- 1998
26. Protein pieces of adipose tissue secretory puzzle
- Author
-
Neşe Tunçel, Fatma Tore, BAİBÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, and Töre, Fatma
- Subjects
Inflammation ,medicine.medical_specialty ,Adiponectin ,Cardiometabolic Diseases ,Leptin ,Adipose tissue ,Adipokine ,General Medicine ,Biology ,Atherosclerosis ,General Biochemistry, Genetics and Molecular Biology ,Energy homeostasis ,Endocrinology ,Adipokines ,Neurotrophic factors ,Internal medicine ,medicine ,Tumor necrosis factor alpha ,Resistin ,Obesity - Abstract
Over the past decade, the paradigm shift of adipose tissue as being far beyond its pivotal role in lipid and energy homeostasis has been increasingly recognized. Arguably, adipocytes as well as other adipose cells are at present considered bona fide secretory cell types, using pleiocrine pathways for delivery of multiple signaling proteins designated adipokines. Transcriptomic and proteomic studies "upregulate" more than hundred adipokines that are synthesized, stored, and released by adipose tissue cells. However, the functional description of adipose-secreted proteins look like an incomplete puzzle. Here we describe only adipsin, adiponectin, leptin, resistin, visfatin, tumor necrosis factor-alpha, interleukin-6, plasminogen activator inhibitor type 1, nerve growth factor, brain-derived neurotrophic factor, and metallothioneins, and focus on their implications for the pathogenesis of various diseases besides obesity and related disorders. Accordingly, a horizon of the adipopharmacology of disease is outlined. © Bulgar ian Society for Cell Biology.
- Published
- 2007
27. Sympathetic skin responses of the face and neck evoked by electrical stimulation
- Author
-
Sule Aydin Turkoglu, Ayhan Ozturk, Nebil Yildiz, Serpil Yildiz, and Fatma Tore
- Subjects
Adult ,Male ,Sympathetic nervous system ,Sympathetic Nervous System ,Adolescent ,Stimulation ,Stimulus (physiology) ,Wrist ,sympathetic skin response ,Cellular and Molecular Neuroscience ,Reaction Time ,medicine ,Humans ,electrical stimulation ,Skin ,Endocrine and Autonomic Systems ,business.industry ,Upper lip ,face ,food and beverages ,Anatomy ,neck ,Electric Stimulation ,Median nerve ,Autonomic nervous system ,medicine.anatomical_structure ,gradual amplitude increase ,Female ,Sympathetic innervation ,Neurology (clinical) ,business - Abstract
Aydin Turkoglu, Sule/0000-0001-8616-832X WOS: 000247979400012 PubMed: 17383240 The sympathetic skin responses (SSRs) were recorded from different facial regions and neck in 25 subjects evoked by electrical stimulation of the median nerve at the wrist. Recordings from all regions were cross-compared with each other and within right and left sides individually. In one subject postauricular SSR, and in another subject upper lip SSR could not be elicited on both sides. Other responses could be obtained in all the remaining subjects. In I I subjects, the responses did not appear by the first stimulus, and began to appear by repeated stimuli. Mean latencies and the highest amplitudes of the responses were similar for both sides. Gradual amplitude increase was observed in the first three or four set of responses in 20 subjects, although the stimulus intensity was constant. In conclusion, face and neck SSRs are symmetric, can be evoked by electrical stimulation and can be used to investigate the sympathetic innervation of these areas. (C) 2007 Elsevier B.V. All rights reserved.
- Published
- 2007
28. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects
- Author
-
Dilek Dogrukol-Ak, Fatma Tore, and Neşe Tunçel
- Subjects
endocrine system ,medicine.medical_specialty ,Vasoactive intestinal peptide ,Central nervous system ,Molecular Sequence Data ,Secretin receptor family ,Secretin family ,Blood–brain barrier ,Secretin ,Internal medicine ,Drug Discovery ,Medicine ,Animals ,Humans ,Amino Acid Sequence ,Pharmacology ,business.industry ,Neuropeptides ,Growth hormone–releasing hormone ,medicine.anatomical_structure ,Endocrinology ,Gastrointestinal hormone ,Blood-Brain Barrier ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Nervous System Diseases ,business ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues. The family members that are released into blood from periphery, especially gut, circulate the brain and they can cross the blood brain barrier. On the other hand, some of the members of this family that present in the brain, can cross from brain to blood and reach the peripheral targets. VIP, secretin, GLP(1), and PACAP 27 are transported into the brain by transmembrane diffusion, a non-saturable mechanism. However, uptake of PACAP 38 into the brain is saturable mechanism. While there is no report for the passage of GIP, GLP(2), and PHM, there is only one report that shows, glucagon and GHRH can cross the BBB. The passage of VIP/PACAP/secretin family members opens up new horizon for understanding of CNS effects of peripherally administrated peptides. There is much hope that those peptides may prove to be useful in the treatment of serious neurological diseases such as Alzheimer's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS related neuropathy, diabetic neuropathy, autism, stroke and nerve injury. Their benefits in various pathophysiologic conditions undoubtly motivate the development of a novel drug design for future therapeutics.
- Published
- 2004
29. Protective effect of vasoactive intestinal peptide on testicular torsion-detorsion injury: association with heparin-containing mast cells
- Author
-
Muzaffer Tunçel, Neşe Tunçel, Dilek Ak, Fatma Tore, Cavit Can, Onur Uysal, Firdevs Gürer, Anadolu Üniversitesi, Eczacılık Fakültesi, Analitik Kimya Anabilim Dalı, and Ak, Dilek
- Subjects
Male ,medicine.medical_specialty ,Urology ,Vasoactive intestinal peptide ,Drug Evaluation, Preclinical ,medicine.disease_cause ,Cytoplasmic Granules ,Nitric Oxide ,Antioxidants ,Nitric oxide ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Internal medicine ,Malondialdehyde ,Testis ,medicine ,Testicular torsion ,Animals ,Mast Cells ,Spermatic Cord Torsion ,business.industry ,Heparin ,Superoxide Dismutase ,Anti-Inflammatory Agents, Non-Steroidal ,Degranulation ,medicine.disease ,Mast cell ,Catalase ,Rats ,Oxidative Stress ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Reperfusion Injury ,business ,Oxidative stress ,Injections, Intraperitoneal ,medicine.drug ,Vasoactive Intestinal Peptide - Abstract
WOS: 000220538100058, PubMed ID: 14751391, Objectives. To elucidate the action of vasoactive intestinal peptide (VIP) on detorsion injury and the heterogeneity of mast cells in the testes of rats. Methods. Prepubertal male Sprague-Dawley rats were used in six groups. Group I was the control group (sham operation); group 2 had 2 hours of torsion; group 3, 2 hours of torsion and 1 hour of detorsion after administration of saline; group 4 had 2 hours of torsion and 4 hours of detorsion after administration of saline; group 5, 2 hours of torsion and 1 hour of detorsion after administration of intraperitoneal VIP (25 ng/kg); and group 6, 2 hours of torsion and 4 hours of detorsion after intraperitoneal VIP. The 2 hours of torsion was created by rotating the right testis 7200 in a clockwise direction. VIP (25 ng/kg) was injected intraperitoneally 1 minute before the 1 and 4 hours of detorsion. At the end of the experiment, catalase enzyme activity was measured polarographically, and superoxide dismutase, malondialdehyde, and protein were measured spectrophoto metrically. Nitric oxide was measured by capillary electrophoresis in the testicular tissue. Routine histologic examination of testicular mast cells was done under light microscopy; the histochemistry was also analyzed. Results. Torsion significantly induced oxidative stress, mast cell degranulation, and tissue damage. Detorsion attenuated oxidative stress without any diminution of the histologic damage to the tissue. VIP significantly protected the testicular tissue from detorsion injury. It also inhibited mast cell activity while increasing the heparin content. Conclusions. VIP can protect testicular tissue from detorsion injury. Heparin-containing mast cells seem to be important mediator cells for this protection
- Published
- 2004
30. Cold exposure and adipose nitric oxide and mast cells: influence on aorta contractility
- Author
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George N. Chaldakov, Neşe Tunçel, Arın Gül Dal, Fatma Tore, Varol Sahinturk, Esin Peker, Erol Şener, and Muzaffer Tunçel
- Subjects
medicine.medical_specialty ,Aorta ,Vascular smooth muscle ,Adipose tissue ,Biology ,Mast cell ,Contractility ,medicine.anatomical_structure ,Endocrinology ,medicine.artery ,Internal medicine ,Brown adipose tissue ,medicine ,Thoracic aorta ,medicine.symptom ,General Agricultural and Biological Sciences ,Vasoconstriction - Abstract
Both nitric oxide (NO) and mast cells play important roles in adipose and vascular tissue biology. Chronic cold stress decreases the sensitivity of vascular smooth muscle to various contractile agents including norepinephrine (NE). In our previous cold exposure study we found that the contractile response of isolated rat aortas to NE was significantly reduced, and the number of rat aortic adventitial mast cells decreased. Histologically and functionally, white and brown adipose tissue (WAT and BAT) can be distinguished. Beyond its significance in energy store/release and heat production, adipose tissue secretes multiple signaling molecules that have endocrine and paracrine role in the regulation of vascular functions. The aims of the present study were to examine chronic cold exposure-induced alterations in (i) the concentration of NO released from selected regions of WAT and BAT in female and male rats, (ii) the histochemistry of white and brown adipose mast cells, and (iii) whether adipose-derived NO affects the contraction of isolated rat aorta to NE. Twelve females and 12 males Spraque-Dawley rats (150-200 g body weight) were used. The rats were exposed to a cold/freely moving stress for 2 hours each day for 5 consecutive days. At the end of cold exposure, the rats were sacrificed, and samples of thoracic aorta with associated periadventitial adipose tissue (tunica adiposa) were obtained. WAT and BAT were isolated from subcutaneous abdominal and interscapular areas, respectively. The concentration of NO was measured by capillary electrophoresis and mast cells were evaluated histochemically. The response of aorta smooth muscles to NE was recorded in the isolated organ bath. To determine whether adipose-derived NO affects aorta contraction to NE, cumulative dose response curves to NE (10 -8 -10 -3 M) were obtained with or without isolated WAT/BAT suspended in the organ bath medium. In control animals, a gender-related significant difference in NO production in both WAT and BAT was found, NO levels being significantly higher in female than male rats. Data from the contractile response of isolated aorta to NE suggest that receptor affinity to NE is significantly different between female and male controls. Presence of BAT and WAT (isolated from cold-exposure animals) in the bath changed the response of aorta smooth muscle to NE. Displaying a gender dimorphism, BAT/WAT-derived NO, or other vasorelaxing factors, seem to reduce receptor density and/or affinity to NE. Adipose mast cell histochemistry also showed diversity in respect to subtype, gender, and cold exposure. Altogether, we found (i) a gender difference in adipose-released NO and in adipose mast cell histochemistry to cold exposure, and (ii) peripheral adipose tissues affect aortic contractile responses to NE likely by a NO-mediated pathway during cold exposure, suggesting that adipose tissue may limit cold-induced excessive vasoconstriction. Our ongoing study aims at the evaluation of whether aortic tunica adiposa itself could also contribute to this phenomenon. Adipobiology 2009; 1: 67-75.
- Published
- 2009
31. The effect of vasoactive intestinal peptide (VIP) and inhibition of nitric oxide (NO) synthase on antioxidant enzyme activities and lipid peroxidation of kidney and liver tissue of rats exposed to endotoxin shock
- Author
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Muzaffer Tunçel, Dilek Ak, Fatma Tore, and Neşe Tunçel
- Subjects
chemistry.chemical_classification ,medicine.medical_specialty ,Kidney ,Antioxidant ,medicine.medical_treatment ,Vasoactive intestinal peptide ,Pathology and Forensic Medicine ,Nitric oxide ,Lipid peroxidation ,chemistry.chemical_compound ,Enzyme ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Physiology (medical) ,Internal medicine ,Liver tissue ,No synthase ,medicine - Published
- 1998
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