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  1. AU="Krzysztof Kamiński"
  2. AU="Sharma, Ishna"
  3. AU="Warner, Brit"
  4. AU="JOCHEN SCHÖNGART"
  5. AU="Curdy, Nicolas"
  6. AU="Nkfusai, Claude Ngwayu"
  7. AU="Peng, Yonghan"
  8. AU="Decker, Miriam"
  9. AU="Campbell, Kerry"
  10. AU="Le Deley, Marie-Cécile" AU="Le Deley, Marie-Cécile"
  11. AU="Guan, Shu"

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  1. Artikel ; Online: Antinociceptive and Antiallodynic Activity of Some 3-(3-Methylthiophen-2-yl)pyrrolidine-2,5-dione Derivatives in Mouse Models of Tonic and Neuropathic Pain

    Anna Dziubina / Anna Rapacz / Anna Czopek / Małgorzata Góra / Jolanta Obniska / Krzysztof Kamiński

    International Journal of Molecular Sciences, Vol 23, Iss 4057, p

    2022  Band 4057

    Abstract: Antiseizure drugs (ASDs) are commonly used to treat a wide range of nonepileptic conditions, including pain. In this context, the analgesic effect of four pyrrolidine-2,5-dione derivatives (compounds 3 , 4 , 6 , and 9 ), with previously confirmed ... ...

    Abstract Antiseizure drugs (ASDs) are commonly used to treat a wide range of nonepileptic conditions, including pain. In this context, the analgesic effect of four pyrrolidine-2,5-dione derivatives (compounds 3 , 4 , 6 , and 9 ), with previously confirmed anticonvulsant and preliminary antinociceptive activity, was assessed in established pain models. Consequently, antinociceptive activity was examined in a mouse model of tonic pain (the formalin test). In turn, antiallodynic and antihyperalgesic activity were examined in the oxaliplatin-induced model of peripheral neuropathy as well as in the streptozotocin-induced model of painful diabetic neuropathy in mice. In order to assess potential sedative properties (drug safety evaluation), the influence on locomotor activity was also investigated. As a result, three compounds, namely 3 , 6 , and 9 , demonstrated a significant antinociceptive effect in the formalin-induced model of tonic pain. Furthermore, these substances also revealed antiallodynic properties in the model of oxaliplatin-induced peripheral neuropathy, while compound 3 attenuated tactile allodynia in the model of diabetic streptozotocin-induced peripheral neuropathy. Apart from favorable analgesic properties, the most active compound 3 did not induce any sedative effects at the active dose of 30 mg/kg after intraperitoneal ( i.p. ) injection.
    Schlagwörter neuropathic pain ; inflammatory pain ; analgesic activity ; anticonvulsants ; pirrolidyne-2,5-dione ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2022-04-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: In Vivo and In Vitro Characterization of Close Analogs of Compound KA-11, a New Antiseizure Drug Candidate

    Marta Andres-Mach / Mirosław Zagaja / Joanna Szala-Rycaj / Aleksandra Szewczyk / Michał Abram / Marcin Jakubiec / Katarzyna Ciepiela / Katarzyna Socała / Piotr Wlaź / Gniewomir Latacz / Nadia Khan / Krzysztof Kaminski

    International Journal of Molecular Sciences, Vol 24, Iss 8302, p

    2023  Band 8302

    Abstract: Epilepsy is a neurological disorder involving a number of disease syndromes with a complex etiology. A properly matched antiseizure drug (ASD) gives remission in up to 70% of patients. Nevertheless, there is still a group of about 30% of patients ... ...

    Abstract Epilepsy is a neurological disorder involving a number of disease syndromes with a complex etiology. A properly matched antiseizure drug (ASD) gives remission in up to 70% of patients. Nevertheless, there is still a group of about 30% of patients suffering from drug-resistant epilepsy. Consequently, the development of new more effective and/or safer ASDs is still an unmet clinical need. Thus, our current studies were focused on the structural optimization/modifications of one of the leading compounds, KA-11 , aiming at the improvement of its antiseizure activity. As a result, we designed and synthesized two close analogs with highly pronounced drug-like physicochemical properties according to in silico predictions, namely KA-228 and KA-232 , which were subsequently tested in a panel of animal seizure models, i.e., MES, 6 Hz (32 mA), sc PTZ and iv PTZ. Among these compounds, KA-232 , which was designed as a water-soluble salt, was distinctly more effective than KA-228 and assured similar antiseizure protection as its chemical prototype KA-11 . With the aim of a more detailed characterization of both new molecules, in vitro binding tests were performed to evaluate the potential mechanisms of action. Furthermore, KA-232 was also evaluated in several ADME-Tox studies, and the results obtained strongly supported its drug-like potential. The proposed chemical modification of KA-11 enabled the identification of new pharmacologically active chemotypes, particularly water-soluble KA-232 , which, despite the lack of better efficacy than the leading compound, may be used as a chemical prototype for the development of new ASDs, as well as substances potentially active in other neurological or neurodegenerative conditions.
    Schlagwörter antiseizure drugs ; drug development ; acute seizure models ; physicochemical descriptors ; leading compound optimization ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2023-05-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Preclinical Assessment of A New Hybrid Compound C11 Efficacy on Neurogenesis and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice

    Marta Andres-Mach / Aleksandra Szewczyk / Mirosław Zagaja / Joanna Szala-Rycaj / Marta Kinga Lemieszek / Maciej Maj / Michał Abram / Krzysztof Kaminski

    International Journal of Molecular Sciences, Vol 22, Iss 3240, p

    2021  Band 3240

    Abstract: Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the in vitro evaluation of potential ... ...

    Abstract Status epilepticus (SE) is a frequent medical emergency that can lead to a variety of neurological disorders, including cognitive impairment and abnormal neurogenesis. The aim of the presented study was the in vitro evaluation of potential neuroprotective properties of a new pyrrolidine-2,5-dione derivatives compound C11, as well as the in vivo assessment of the impact on the neurogenesis and cognitive functions of C11 and levetiracetam (LEV) after pilocarpine (PILO)-induced SE in mice. The in vitro results indicated a protective effect of C11 (500, 1000, and 2500 ng/mL) on astrocytes under trophic stress conditions in the MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) test. The results obtained from the in vivo studies, where mice 72 h after PILO SE were treated with C11 (20 mg/kg) and LEV (10 mg/kg), indicated markedly beneficial effects of C11 on the improvement of the neurogenesis compared to the PILO control and PILO LEV mice. Moreover, this beneficial effect was reflected in the Morris Water Maze test evaluating the cognitive functions in mice. The in vitro confirmed protective effect of C11 on astrocytes, as well as the in vivo demonstrated beneficial impact on neurogenesis and cognitive functions, strongly indicate the need for further advanced molecular research on this compound to determine the exact neuroprotective mechanism of action of C11.
    Schlagwörter anticonvulsant ; neuroprotection ; neurogenesis ; pilocarpine ; antiepileptic drugs ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 150
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: C-11, a New Antiepileptic Drug Candidate

    Mirosław Zagaja / Aleksandra Szewczyk / Joanna Szala-Rycaj / Grzegorz Raszewski / Magdalena Chrościńska-Krawczyk / Michał Abram / Krzysztof Kamiński / Marta Andres-Mach

    Molecules, Vol 26, Iss 3144, p

    Evaluation of the Physicochemical Properties and Impact on the Protective Action of Selected Antiepileptic Drugs in the Mouse Maximal Electroshock-Induced Seizure Model

    2021  Band 3144

    Abstract: C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various ... ...

    Abstract C-11 is a hybrid compound derived from 2-(2,5-dioxopyrrolidin-1-yl) propanamide, with a wide spectrum of anticonvulsant activity and low neurotoxicity. The aim of this study was to determine the effects of C-11 on the protective action of various antiepileptic drugs (i.e., carbamazepine CBZ, lacosamide LCM, lamotrigine LTG, and valproate VPA) against maximal electroshock-induced seizures (MES) in mice, as well as its neuroprotective and physicochemical/pharmacokinetic properties. Results indicate that C-11 (30 mg/kg, i.p.) significantly enhanced the anticonvulsant action of LCM ( p < 0.001) and VPA ( p < 0.05) but not that of CBZ and LTG in the MES test. Neither C-11 (30 mg/kg) alone nor its combination with other anticonvulsant drugs (at their ED 50 values from the MES test) affected motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength and passive avoidance tests, respectively. Pharmacokinetic characterization revealed that C-11 had no impact on total brain concentrations of LCM or VPA in mice. Qualitative analysis of neuroprotective properties of C-11, after a single administration of pilocarpine, revealed no protective effect of this substance in the tested animals. Determination of physicochemical descriptors showed that C-11 meets the drug-likeness requirements resulting from Lipinski and Veber’s rules and prediction of gastrointestinal absorption and brain penetration, which is extremely important for the CNS-active compounds.
    Schlagwörter antiepileptic drugs ; maximal electroshock-induced seizures ; pharmacokinetic/pharmacodynamic interaction ; neuroprotection ; physicochemical descriptors ; Organic chemistry ; QD241-441
    Thema/Rubrik (Code) 630
    Sprache Englisch
    Erscheinungsdatum 2021-05-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: Synthesis, Anticonvulsant, and Antinociceptive Activity of New 3-(2-Chlorophenyl)- and 3-(3-Chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides

    Małgorzata Góra / Anna Czopek / Anna Rapacz / Anna Gębska / Katarzyna Wójcik-Pszczoła / Elżbieta Pękala / Krzysztof Kamiński

    Molecules, Vol 26, Iss 1564, p

    2021  Band 1564

    Abstract: The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: ... ...

    Abstract The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole ( sc PTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione ( 6 ) showed more beneficial ED 50 and protective index values than the reference drug—valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds—namely, 6 and 19 —was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABA A and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.
    Schlagwörter anticonvulsant activity ; antinociceptive activity ; pyrrolidine-2,5-dione ; amides ; Organic chemistry ; QD241-441
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: New Phenylglycinamide Derivatives with Hybrid Structure as Candidates for New Broad-Spectrum Anticonvulsants

    Marcin Jakubiec / Michał Abram / Mirosław Zagaja / Marta Andres-Mach / Aleksandra Szewczyk / Gniewomir Latacz / Bartłomiej Szulczyk / Katarzyna Socała / Dorota Nieoczym / Piotr Wlaź / Cameron S. Metcalf / Karen Wilcox / Rafał M. Kamiński / Krzysztof Kamiński

    Cells, Vol 11, Iss 1862, p

    2022  Band 1862

    Abstract: In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104 , that was previously discovered by our group. Consequently, a ... ...

    Abstract In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104 , that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities). The most potent compounds 53 and 60 displayed the following pharmacological profile: ED 50 = 89.7 mg/kg (MES), ED 50 = 29.9 mg/kg (6 Hz, 32 mA), ED 50 = 68.0 mg/kg (6 Hz, 44 mA), and ED 50 = 73.6 mg/kg (MES), ED 50 = 24.6 mg/kg (6 Hz, 32 mA), and ED 50 = 56.3 mg/kg (6 Hz, 44 mA), respectively. Additionally, 53 and 60 were effective in the iv PTZ seizure threshold and had no influence on the grip strength and body temperature in mice. The in vitro binding and functional assays indicated a multimodal mechanism of action for 53 and 60 . These molecules, beyond TRPV1 antagonism, inhibited calcium currents and fast sodium currents in patch-clamp assays. Further studies proved beneficial in vitro ADME-Tox properties for 53 and 60 (i.e., high metabolic stability, weak influence on CYPs, no neurotoxicity, etc.). Overall, 53 and 60 seem to be interesting candidates for future preclinical development in epilepsy and pain indications due to their interaction with the TRPV1 channel.
    Schlagwörter hybrid molecules ; multimodal/multi-target compounds ; amino acid derivatives ; antiseizure activity ; in vitro binding/functional studies ; ADME-Tox properties ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 540 ; 500
    Sprache Englisch
    Erscheinungsdatum 2022-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: The Search for New Anticonvulsants in a Group of (2,5-Dioxopyrrolidin-1-yl)(phenyl)Acetamides with Hybrid Structure—Synthesis and In Vivo/In Vitro Studies

    Michał Abram / Marcin Jakubiec / Anna Rapacz / Szczepan Mogilski / Gniewomir Latacz / Rafał M. Kamiński / Krzysztof Kamiński

    International Journal of Molecular Sciences, Vol 21, Iss 8780, p

    2020  Band 8780

    Abstract: Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a ... ...

    Abstract Epilepsy belongs to the most common and debilitating neurological disorders with multifactorial pathophysiology and a high level of drug resistance. Therefore, with the aim of searching for new, more effective, and/or safer therapeutics, we discovered a focused series of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant properties. We applied an optimized coupling reaction yielding several hybrid compounds that showed broad-spectrum activity in widely accepted animal seizure models, namely, the maximal electroshock (MES) test and the psychomotor 6 Hz (32 mA) seizure model in mice. The most potent anticonvulsant activity and favorable safety profile was demonstrated for compound 30 (median effective dose (ED 50 ) MES = 45.6 mg/kg, ED 50 6 Hz (32 mA) = 39.5 mg/kg, median toxic dose (TD 50 ) (rotarod test) = 162.4 mg/kg). Anticonvulsant drugs often show activity in pain models, and compound 30 was also proven effective in the formalin test of tonic pain, the capsaicin-induced pain model, and the oxaliplatin (OXPT)-induced neuropathic pain model in mice. Our studies showed that the most plausible mechanism of action of 30 involves inhibition of calcium currents mediated by Cav 1.2 (L-type) channels. Importantly, 30 revealed high metabolic stability on human liver microsomes, negligible hepatotoxicity, and relatively weak inhibition of CYP3A4, CYP2D6, and CYP2C9 isoforms of cytochrome P450, compared to reference compounds. The promising in vivo activity profile and drug-like properties of compound 30 make it an interesting candidate for further preclinical development.
    Schlagwörter hybrid molecules ; pyrrolidine-2,5-dione ; anticonvulsant activity ; antinociceptive activity ; in vitro binding/functional studies ; absorption ; distribution ; metabolism ; excretion ; toxicity (ADME-Tox) properties ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 540
    Sprache Englisch
    Erscheinungsdatum 2020-11-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta

    Ewa Wietrak / Krzysztof Kamiński / Bożena Leszczyńska-Gorzelak / Jan Oleszczuk

    BioMed Research International, Vol

    Preliminary Report

    2015  Band 2015

    Abstract: Introduction. Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction ...

    Abstract Introduction. Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR) and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA) promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. Materials and Methods. We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group). The control group consisted of 50 women who did not receive such supplementation (control group). We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. Results. Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. Conclusions. We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.
    Schlagwörter Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2015-01-01T00:00:00Z
    Verlag Hindawi Limited
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  9. Artikel ; Online: Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides

    Michał Abram / Marcin Jakubiec / Anna Rapacz / Szczepan Mogilski / Gniewomir Latacz / Bartłomiej Szulczyk / Małgorzata Szafarz / Katarzyna Socała / Dorota Nieoczym / Elżbieta Wyska / Piotr Wlaź / Rafał M. Kamiński / Krzysztof Kamiński

    International Journal of Molecular Sciences, Vol 22, Iss 13092, p

    2021  Band 13092

    Abstract: We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure ...

    Abstract We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model ( sc PTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED 50 MES = 49.6 mg/kg, ED 50 6 Hz (32 mA) = 31.3 mg/kg, ED 50 sc PTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED 50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.
    Schlagwörter pyrrolidine-2,5-dione ; salts ; hybrid compounds ; anticonvulsant activity ; antinociceptive activity ; electrophysiology ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Thema/Rubrik (Code) 540 ; 500
    Sprache Englisch
    Erscheinungsdatum 2021-12-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Foetal and neonatal alloimune thrombocytopenia as a rare exapmle of thrombocytopenia in newborn

    Maciej Kamiński / Paulina Grzesik / Monika Długoń / Maciej Majsterek / Żaneta Kimber-Trojnar / Krzysztof Kamiński / Bożena Leszczyńska-Gorzelak

    Journal of Education, Health and Sport, Vol 8, Iss

    2018  Band 12

    Abstract: Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antigenic incompatibility of platelets between a pregnant woman and her child, resulting in producing antibodies by a mother against specific antigens (HPA- Human Platelet Antigens) ... ...

    Abstract Foetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by antigenic incompatibility of platelets between a pregnant woman and her child, resulting in producing antibodies by a mother against specific antigens (HPA- Human Platelet Antigens) located on fetal platelets inherited from his father. The aim of this study is to present a 29-year-old patient in the 40th week of the second pregnancy admitted to the Department after rupturing of membranes. A male infant was born vaginally with numerous petechiae, bruising and yellowish skin colour. Due to severe thrombocytopenia 1 unit of leucocyte-reduced, irradiated, reconstituted platelet concentrate (LRIRPC) of blood group O RhD (+), suspended in plasma type AB was ordered. Human immunoglobulin (Kiovig preparation) was transfused. A check exam of complete blood count of the newborn revealed 5 x 103/µL of platelets count 4 hours after the transfusion. Following transfusions of LRIRPC and Kiovig were ordered. Again with no therapeutic effect. The newborn’s HPA antigens were identified as: 1a/b; 2a/a; 3a/a; 5a/a; 4a/a; 15b/b, platelet antibodies derived from the mother were found in his serum. After transfusion of 1 unit of HPA-1b/b LRIRPC at 37 hours of the newborn’s life the platelet count increased to 67 x103/µL. The treatment with dexamethasone and Kiovig was continued. The infant was discharged in good condition in the 33rd day of life. The FNAIT diagnostics is usually carried out only as a result of clinical manifestations of thrombocytopenia in the newborn. There was a possibility for all pregnant women from 8 weeks of pregnancy to have their blood tested for the presence of HPA-1a antigen in the period between October of 2013 to January of 2017 in Poland. It made it possible to nominate HPA-1a negative women.
    Schlagwörter Thrombocytopenia ; HPA ; FNAIT ; Education ; L ; Sports ; GV557-1198.995 ; Medicine ; R
    Thema/Rubrik (Code) 630
    Sprache Englisch
    Erscheinungsdatum 2018-12-01T00:00:00Z
    Verlag Kazimierz Wielki University
    Dokumenttyp Artikel ; Online
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