The Anticonvulsant Enaminone E139 Attenuates Paclitaxel-Induced Neuropathic Pain in Rodents

The enaminone methyl 4-(4′-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139) has anticonvulsant activities. It has been reported to have a better safety profile than some anticonvulsant drugs. Since some anticonvulsant drugs are used in the management of neuropathic pain, we evaluated the effects of E139 in rodent models of acute pain and paclitaxel-induced neuropathic pain. The reaction latency to thermal stimuli (hot-plate test) of BALB/c mice was recorded before and after intraperitoneal treatment with paclitaxel (2 mg/kg, i.p. for 5 consecutive days), and after treatment with E139 (0.1–40 mg/kg), amitriptyline (10 mg/kg), and gabapentin (10 and 30 mg/kg). Mechanical allodynia in paclitaxel-treated Sprague Dawley (SD) rats was measured using a dynamic plantar aesthesiometer before and after treatment with E139 (10 and 20 mg/kg) or its vehicle for four consecutive days from day 7 after first administration of paclitaxel (16 mg/kg on two alternate days). Administration of E139 (10–40 mg/kg) produced antinociceptive activity against thermal nociception in naïve mice. Treatment with E139, amitriptyline, or gabapentin reduced paclitaxel-induced thermal hyperalgesia. E139 reduced paclitaxel-induced mechanical allodynia, with the effects lasting longer (24 h) after repetitive dosing. Our results indicate that E139 has antinociceptive activity and attenuates paclitaxel-induced neuropathic pain in rodents

X-ray crystallographic and theoretical studies of an anticonvulsant enaminone:methyl 4-(4'-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate

Objective: The aims of this study were to establish the structure of the potent anticonvulsant enaminone methyl 4-(4′-bromophenyl)amino-6-methyl-2- oxocyclohex-3-en-1-oate (E139), and to determine the energetically preferred conformation of the molecule, which is responsible for the biological activity. Materials and Methods: The structure of the molecule was determined by X-ray crystallography. Theoretical ab initio calculations with different basis sets were used to compare the energies of the different enantiomers and to other structurally related compounds. Results: The X-ray crystal structure revealed two independent molecules of E139, both with absolute configuration C11(S), C12(R), and their inverse. Ab initio calculations with the 6-31G, 3-21G and STO-3G basis sets confirmed that the C11(S), C12(R) enantiomer with both substituents equatorial had the lowest energy. Compared to relevant crystal structures, the geometry of the theoretical structures shows a longer C-N and shorter C=O distance with more cyclohexene ring puckering in the isolated molecule. Conclusion: Based on a pharmacophoric model it is suggested that the enaminone system HN-C=C-C=O and the 4-bromophenyl group in E139 are necessary to confer anticonvulsant property that could lead to the design of new and improved anticonvulsant agents. Copyright © 2003 S. Karger AG, Basel

Assessment of Groundwater Drinking Sources in Eku and Its Environs, in the Niger-Delta Region of Nigeria

قيمت هذه الدراسة جودة مصادر مياه الشرب المحفورة يدويا في ايكو وضواحيها. باستخدام طريقة مؤشر جودة المياه الحسابية. تم جمع عينات المياه من الآبار المحفورة يدويًا في هذه المواقع والتي أعطت قيمًا للمعلمات التي تم تحليلها. درجة الحرارة 26 - 30، الأكسجين المذاب (D.O) 5.2-8 ملجم / لتر، الطلب على الأكسجين البيولوجي (BOD) 5.2-8 (ملجم / لتر)، التوصيل الكهربائي (EC) 77-119 (µS / سم). إجمالي المواد الصلبة العالقة (TSS) 20000-120000 (مجم / لتر) ، الرقم الهيدروجيني 5.31-7.09 ، الفوسفات 2-9.2 (مجم / لتر) ، القلوية 28-160 (مجم / لتر) ، التعكر ، 0.02 -0.19 (NTU) المجموع coliform 2 -48 (cfu / ml) وعدد الفطريات 1-502. كانت الاختلافات في قيم هذه المعلمات مهمة فقط للفوسفات والقلوية والعكارة بين Samagidi و Okuechi عند مستوى معنوية p≤0.05. أوصت NSDWQ / WHO باستخدام D.O، BOD، الفوسفات، إجمالي القولون ومستوى TSS، مما يجعل مصادر المياه هذه غير مناسبة لأغراض مياه الشرب. كشف التحليل العنقودي عن ثلاث مجموعات عنقودية؛ المجموعة 1 (Eku2) والمجموعة 2 (Samagidi) والمجموعة 3 (Eku1 و Okuechi) ، بينما أظهر تحليل العوامل ارتباطًا قويًا مع الأس الهيدروجيني ، والأكسجين المذاب ، والأكسجين الحيوي ، والفوسفات ، والتوصيلية ، والتعداد القولوني الكلي والفطريات مع مصادر المياه في الدراسة المحطات. WQI المحسوب لمصادر المياه هذه هو 107.56 و 95.18 و 103.45 و 110.36 لـ Eku I و Samagidi و Eku 2 و Okuechi ، على التوالي ، وتصنيفها على أنها ذات نوعية مياه سيئة للغاية وغير مناسبة لأغراض الشرب. يعتبر التخلص العشوائي من النفايات والجريان السطحي وسوء المرافق الصحية والطبيعة المكشوفة لهذه الآبار من العوامل الرئيسية في تدهور هذه الآبار.This study assessed the quality of hand-dug drinking water sources in Eku and its environs at Eku I, Samagidi, Eku 2, and Okuechi, using the weighted arithmetic water quality index method. Water samples collected from hand-dug wells at these locations returned values for analyzed parameters. Temperature 26 – 30(⁰C), dissolved Oxygen (D.O) 5.2-8mg/l, biological oxygen demand (BOD) 5.2-8(mg/l), Electrical Conductivity (EC) 77-119(µS/cm), Total suspended solids were  (TSS) 20000-120000(mg/l), pH 5.31-7.09, Phosphates 2-9.2(mg/l), Alkalinity 28-160(mg/l), Turbidity, 0.02 -0.19(NTU) Total coliform 2 -48 (cfu/ml) and fungal count 1-502. Variations in the values of these parameters were only significant for phosphate, alkalinity, and turbidity between Samagidi and Okuechi at a level of significance of p≤0.05. D.O, BOD, phosphates, total coliform and TSS levels, exceeded standards recommended by NSDWQ/WHO, rendering these water sources unsuitable for drinking purposes. Cluster analysis revealed three cluster groups; cluster 1(Eku2), cluster 2(Samagidi), and cluster 3(Eku1 and Okuechi), while factor analysis showed a strong correlation with pH, D.O, BOD, phosphate, conductivity, total coliform and fungal counts with water sources in the study stations. The calculated WQI for these water sources is 107.56, 95.18, 103.45, and 110.36 for Eku I, Samagidi, Eku 2, and Okuechi, respectively, classifying them as very poor water quality and unsuitable for drinking purposes. Indiscriminate waste disposal, surface runoff and poor sanitary facilities, and the exposed nature of these wells are major contributors to the deterioration of these wells

Analysis of Entrepreneurship Development in Agriculture Among Female Groundnut Farmers in Enugu State

This paper examines the entrepreneurship development in agriculture among female groundnut farmers in Enugu state. Eighty female farmers were selected using multi-stage random sampling techniques. Well structured questionnaire was the main tool for data collection. Data collected were analyzed using descriptive statistical tools, and five point likert scale rating. Results showed that their mean age was 43 years. Majority were married with average household size of five persons. Farmers had small farm sizes of 1.7 hectares. Their average income per farming season was N117000. Majority of the female farmers identified need to increase their income, desire to succeed; need to care for their family and desire to be financially independent as the key drive to entrepreneurship development in groundnut production. They complained of poor access to entrepreneurship education and information, and inadequate capital as major challenges hindering their entrepreneurship development. Despite the challenges, entrepreneurship drive and participation was high. It was recommended that effective and adequate policies and programmes on entrepreneurship should be developed especially for female farmers. Entrepreneurship education/training at all levels to ensure capacity building was also advocated. Most importantly, government should provide soft loans and grants to female farmers as a way to enhance their entrepreneurial spirit and development for national food security. Keywords: Entrepreneurship development, Groundnut production, Female farmers, Challenge

Antidepressant drugs and teenage suicide in Hungary: Time trend and seasonality analysis

K

3-(4-Chloro­anilino)-2,5-dimethyl­cyclo­hex-2-en-1-one

In the title compound, C14H16ClNO, the dihedral angle between the benzene ring and the conjugated part of the cyclo­hexene ring is 61.7 (2)°. Part of the cyclo­hexene ring and one of the attached methyl groups are disordered over two orientations with occupancies of 0.602 (7) and 0.398 (7). In addition, the crystal studied was a racemic twin [Flack parameter = 0.58 (4)]. In the crystal, the mol­ecules are linked into chains in the b-axis direction by inter­molecular N—H⋯O hydrogen bonds. C—H⋯O and C—H⋯Cl inter­actions are also observed

2,5-Dimethyl-3-[4-(trifluoro­meth­oxy)anilino]­cyclo­hex-2-enone

In the title compound, C15H16F3NO2, the dihedral angle between the benzene ring and the conjugated part of the cyclo­hexene ring is 60.00 (8)°. The non-conjugated part of the cyclohexene ring and the trifluoro­methyl group are both disordered over two sets of sites with occupancies of 0.835 (2) and 0.165 (2). In the crystal, mol­ecules are linked into chains along [010] by inter­molecular N—H⋯O hydrogen bonds. Weak inter­molecular C—H⋯O inter­actions also occur