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1.
PLoS One ; 19(4): e0299021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593148

RESUMO

Developing chaotic systems-on-a-chip is gaining much attention due to its great potential in securing communication, encrypting data, generating random numbers, and more. The digital implementation of chaotic systems strives to achieve high performance in terms of time, speed, complexity, and precision. In this paper, the focus is on developing high-speed Field Programmable Gate Array (FPGA) cores for chaotic systems, exemplified by the Lorenz system. The developed cores correspond to numerical integration techniques that can extend to the equations of the sixth order and at high precision. The investigation comprises a thorough analysis and evaluation of the developed cores according to the algorithm complexity and the achieved precision, hardware area, throughput, power consumption, and maximum operational frequency. Validations are done through simulations and careful comparisons with outstanding closely related work from the recent literature. The results affirm the successful creation of highly efficient sixth-order Lorenz discretizations, achieving a high throughput of 3.39 Gbps with a precision of 16 bits. Additionally, an outstanding throughput of 21.17 Gbps was achieved for the first-order implementation coupled with a high precision of 64 bits. These outcomes set our work as a benchmark for high-performance characteristics, surpassing similar investigations reported in the literature.


Assuntos
Algoritmos , Computadores , Comunicação
2.
Arch Pharm (Weinheim) ; 357(3): e2300513, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38148301

RESUMO

A series of novel N-aryl-5-aryl-6,7,8,9-tetrahydropyrimido[4,5-b]quinolin-4-amines 4a-4l was synthesized as potential anticancer agents through Dimroth rearrangement reaction of intermediates 3a-3c. Pyrimido[4,5-b]quinolines 4a-4l showed promising activity against the Michigan Cancer Foundation-7 (MCF-7) cell line, compared with lapatinib as the reference drug. Compounds 4d, 4h, 4i, and 4l demonstrated higher cytotoxic activity than lapatinib, with IC50 values of 2.67, 6.82, 4.31, and 1.62 µM, respectively. Compounds 4d, 4i, and 4l showed promising epidermal growth factor receptor (EGFR) inhibition with IC50 values of 0.065, 0.116, and 0.052 µM, respectively. These compounds were subjected to human epidermal growth factor receptor 2 (HER2) inhibition and showed IC50 values of 0.09, 0.164, and 0.055 µM, respectively. Compounds 4d, 4i, and 4l are good candidates as dual EGFR/HER2 inhibitors. The most active compound, 4l, was subjected to cell-cycle analysis and induced cell-cycle arrest at the S phase. Compound 4l induced apoptosis 60-fold compared with control untreated MCF-7 cells. 4l can inhibit cancer metastasis. It reduced MCF-7 cell infiltration and metastasis by 45% compared with control untreated cells.


Assuntos
Antineoplásicos , Quinolinas , Humanos , Relação Estrutura-Atividade , Lapatinib , Ensaios de Seleção de Medicamentos Antitumorais , Quinolinas/farmacologia , Receptores ErbB/metabolismo
3.
Chem Biol Drug Des ; 102(5): 996-1013, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37527951

RESUMO

A series of N-arylpyrimido[4,5-b]quinolines 3a-e and 2-aryl-2,3-dihydropyrimido[4,5-b]quinoline-4(1H)-ones 5a-e was designed and synthesized as potential anticancer agents against breast cancer. Compounds 3e, 5a, 5b, 5d, and 5e showed promising activity against the MCF-7 cell line. Among them, compound 5b was the most active with IC50 of 1.67 µM. Compound 5b promoted apoptosis and induced cell cycle arrest at S phase. 5b increased the level of pro-apoptotic proteins p53, Bax, and caspase-7 and inhibited the anti-apoptotic protein Bcl-2. Furthermore, all the synthesized compounds were docked into the crystal structure of HER2 (PBD: 3 pp0). Compounds 3e, 5a, 5b, 5d, and 5e showed good energy scores and binding modes. Finally, Compound 5b was evaluated on the HER2 assay and revealed good inhibition with IC50 of 0.073 µM.

4.
Bioorg Chem ; 137: 106638, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37257374

RESUMO

New benzothienopyran and benzothienopyranopyrimidine derivatives were synthesized based on the structural requirements of topoisomerase I inhibitors. All target compounds exhibited strong cytotoxic activity with GI50 range of 70.62 %-87.29 % in one dose NCI (USA) screening against 60 human tumor cell lines. Among the tested derivatives, eight compounds namely 4d, 4e, 4f, 5b, 5e, 6b, 6d, and 6f demonstrated broad spectrum and potent anticancer efficacy in five dose screening against all tested panels. DNA relaxation assay for the latter compounds showed that 4d, 5b, and 6f exhibited excellent inhibitory activity with IC50 range of 2.553-4.495 µM as compared to indenoisoquinoline reference drug (IC50 = 3.911 ± 0.21 µM). Moreover, the most active compounds were investigated for being topoisomerase poisons or catalytic inhibitors using DNA nicking assay. Compounds 4d and 6f were found to be potential Topo I poisons, whereas compound 5b has acted as Topo I suppressor. Analyzing cell cycle and induction of apoptosis for the most active compound 4d, revealed growth arrest at the S phase in MDA-MB-435 cells similarly to indenoisoquinoline reference drug. Additionally, in silico molecular modeling study for eight most active cytotoxic compounds in five dose screening demonstrated interaction with DNA as well as distinctive binding pattern similar to the reference indenoisoquinoline, indicating that the newly discovered targets are supposed to be promising candidates as Topo I inhibitors.


Assuntos
Antineoplásicos , Venenos , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/farmacologia , Proliferação de Células , Antineoplásicos/química , Linhagem Celular Tumoral , Apoptose , DNA , Venenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular
5.
Arch Pharm (Weinheim) ; 355(6): e2100470, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35244962

RESUMO

Pyrazolo[3,4-d]pyrimidine as a bioisostere of purine has drawn considerable attention as a privileged scaffold for the design and discovery of novel drugs. Green synthesis is an emerging area in the field of chemistry that provides economic and environmental benefits as an alternative to traditional methods. The present mini review reflects recent advances in the green synthesis of pyrazolo[3,4-d]pyrimidines, published in the time frame from 2006 to 2019.


Assuntos
Pirazóis , Pirimidinas , Relação Estrutura-Atividade
6.
J Enzyme Inhib Med Chem ; 36(1): 1839-1859, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34338119

RESUMO

A series of [1]benzothieno[2,3-c]pyridines was synthesised. Most compounds were chosen by NCI-USA to evaluate their anticancer activity. Compounds 5a-c showed prominent growth inhibition against most cell lines. 5c was selected at five dose concentration levels. It exhibited potent broad-spectrum anticancer activity with a GI50 of 4 nM-37 µM. Cytotoxicity of 5a-c was further evaluated against prostate, renal, and breast cancer cell lines. 5c showed double and quadruple the activity of staurosporine and abiraterone, respectively, against the PC-3 cell line with IC50 2.08 µM. The possible mechanism of anti-prostate cancer was explored via measuring the CYP17 enzyme activity in mice prostate cancer models compared to abiraterone. The results revealed that 5c suppressed the CYP17 enzyme to 15.80 nM. Moreover, it was found to be equipotent to abiraterone in testosterone production. Cell cycle analysis and apoptosis were performed. Additionally, the ADME profile of compound 5c demonstrated both good oral bioavailability and metabolic stability.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Piridinas/química , Piridinas/farmacologia , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Linhagem Celular Tumoral , Simulação por Computador , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacocinética , Humanos , Masculino , Camundongos , Neoplasias da Próstata/patologia , Piridinas/síntese química , Piridinas/farmacocinética , Análise Espectral/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Bioorg Chem ; 112: 104915, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33905973

RESUMO

A series of new benzo[b]thiophenes 2a-f and benzo[4,5]thieno[3,2-b]pyran derivatives 3a-f and 4a-f were synthesized and their structures were confirmed by elemental analyses and spectral data. All synthesized compounds were evaluated by the National Cancer Institute (NCI, USA) against 60 human tumor cell lines. Compounds 3a-f and 4a-f showed potent cytotoxic effects in one dose assay with mean growth inhibition ranging from 62% to 80%. Six compounds 3a, 3d, 3e, 3f, 4d and 4e were selected by NCI, USA for five dose evaluation against 60 human tumor cell lines. Compounds 3a, 3d, 3e and 3f exhibited very potent and broad spectrum cytotoxicity against almost all cancer cell lines with mean concentration that yield 50% growth inhibition (MG-MID GI50) of 0.1-0.58 µM and mean concentration that produce 100% growth inhibition (MG-MID TGI) of 6.03-10.00 µM. Compounds 4d and 4e exhibited very potent and selective cytotoxic activity against MDA-MB-435 subpanel (melanoma cancer) with GI50 of 0.45 µM and 0.59 µM, respectively. The mechanism of antiproliferative activity was determined for the most active compounds 3a, 3d, 3e, 3f, 4d, and 4evia measuring their half maximal inhibitory concentration (IC50) against topoisomerase I enzyme at different concentrations. Compounds 3a and 3e exhibited excellent activity compared with reference drugs with IC50 of 0.295 µM and 0.219 µM, respectively. Plasmid DNA nicking assay verified that these compounds are topoisomerase I poisons not suppressors. The active compound 3e induced a significant disruption in the cell cycle profile parallel to its effect on apoptosis induction.


Assuntos
Antineoplásicos/farmacologia , DNA Topoisomerases Tipo I/metabolismo , Piranos/farmacologia , Inibidores da Topoisomerase I/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Estrutura Molecular , Piranos/síntese química , Piranos/química , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/síntese química , Inibidores da Topoisomerase I/química
8.
Saudi Med J ; 41(3): 290-295, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114602

RESUMO

OBJECTIVES: To determine relationship between fatigue, depression with the registration in multiple sclerosis (MS) society activity, and stress with the risk developing a new attack in patients with Relapsing remitting MS (RRMS) in the Kingdom of Saudi Arabia (KSA). METHODS: This was a cohort retrospective study conducted in the KSA between July 2018 and July 2019 which included a total of 465 RRMS patients. Data were collected during interviews using the Beck Depression Inventory (BDI) and Modified Fatigue Impacts Scale (MFIS). Demographic and clinical data were also collected. RESULTS: Of 465 participants, 317 expressed psychological stress before the last attack, 67 of whom developed an attack within 4 weeks, and 250 of whom developed an attack after 4 weeks. Significantly lower BDI scores were associated with registration in MS associations (p=0.003, df = 5). Significantly lower MFIS scores were associated with registration in MS associations (p=0.001, df = 5). CONCLUSION: The majority of RRMS patients have a significant fatigue and depression, and there are significant relationships between registration in the MS society and MFIS and BDI scores where patients who officially registered in MS society have lower score in MFIS and BDI. we recommend regular follow-ups with a psychologist and/or registration with MS societies.


Assuntos
Depressão , Fadiga , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Esclerose Múltipla Recidivante-Remitente/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Sistema de Registros , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Estresse Psicológico , Inquéritos e Questionários
9.
Surg Neurol Int ; 11: 460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33408945

RESUMO

BACKGROUND: Biomarkers in supratentorial intracerebral hemorrhage (SICH) enhance the prognosis of the disease. This study aimed to assess the prognosticative grade of S100 calcium-binding protein B (S100B), interleukin-6 (IL-6), and the pro-brain natriuretic peptide (pro-BNP) in SICH outcome prediction. METHODS: Blood samples of 50 SICH patients were analyzed for the biomarkers. The patients were classified into two groups with and without intraventricular hemorrhage (IVH). The following scales including Glasgow Coma Score (GCS), the Barthel index (BI), intracerebral hemorrhage (ICH) score, ICH volume, National Institutes of Health Stroke Scale (NIHSS), Modified Rankin Score (mRS), and length of stay were used to evaluate the severity. RESULTS: The severity scores (NIHSS, GCS, BI, mRI) were significantly higher in SICH patients with IVH versus SICH patients without IVH (P = 0.002, 0.008, 0.001, and 0.03, respectively). Serum levels for a pro-BNP and S100b are significantly higher in SICH patients with IVH versus SICH patients without IVH (P = 0.02 and 0.027, respectively). Multivariate correlations between demographic (age), biomarkers panel (IL-6, S100b, and proBNP), and clinical and severity scores (ICH score, ICH volume, length of hospital stay [LOS], BI, mRS, GCS, and NIHSSS) in all studied patients showed a highly significant correlation between ICH score and pro-BNP (P = 0.04). There was a highly significant correlation between LOS and IL-6 (P = 0.003). CONCLUSION: Pro-BNP, IL-6, and S100b are greatly associated with the presence of IVH that, in turn, correlated well with poor clinical outcome measures.

10.
Eur J Med Chem ; 187: 111926, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812033

RESUMO

A series of new benzothieno[3,2-d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI, USA) evaluated all synthesized compounds against 60 human tumor cell lines. Most of the compounds showed good cytotoxicity against MCF-7 breast cancer cell line and UO-31 renal cancer cell line (growth inhibitory range: 17.88%-68.65%). IC50 of twelve most active compounds was determined against MCF-7 and UO-31 cell lines. Compounds 7, 10, 13, 16 and 17 proved a prominent anticancer activity against tested cell lines (IC50 range 0.23-26.25 µg/mL). IC50 against SIRT2 enzyme was evaluated for the most active compounds to explore the mechanism of antiproliferative activity. The best activity was displayed by compound 7 (IC50 = 2.10 µg/mL), which is 6.6 more potent than cambinol as a reference. Moreover, compound 7 displayed high selectivity against SIRT1 and SIRT2 over SIRT3 in the selectivity studies and displayed twice activity of cambinol in hyperacetylation of α-tubulin protein with IC50 = 32.05 µg/mL. Molecular docking study of the synthesized compounds into SIRT2 active site was performed to rationalize the remarkable SIRT2 inhibitory activity.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Pirimidinas/farmacologia , Sirtuína 2/antagonistas & inibidores , Tiofenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Sirtuína 2/metabolismo , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/química , Células Tumorais Cultivadas
11.
Anticancer Agents Med Chem ; 19(11): 1368-1381, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038080

RESUMO

BACKGROUND: Pyrazolo[3,4-d]pyrimidine scaffold was reported to possess potent cytotoxic and CDK2 inhibitory activity as analogue of roscovitine. OBJECTIVE: To design and synthesize novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidine derivatives as bioisosters of roscovitine with potential cytotoxic and CDK2 inhibitory activity. METHODS: A series of novel 1-(4-flourophenyl)pyrazolo[3,4-d]pyrimidines were designed and synthesized. Structural elucidation for all the newly synthesized compounds was achieved through performing MS, 1H NMR, 13C NMR and IR spectral techniques. Eight compounds were screened for their cytotoxic activity by National Cancer Institute (USA) against 60 different human cancer cell lines. Compounds 2a, 4, 6, 7b, 8a and 8b were further studied through the determination of their IC50 values against the most sensitive cell lines. The inhibitory activities of compounds 2a and 4 were evaluated against CDK2 enzyme. RESULTS: Compound 4 exhibited the most prominent broad-spectrum cytotoxic activity against 42 cell lines representing all human cancer types showing growth inhibition percentages from 53.19 to 99.39. Compound 2a showed promising selectivity against several cell lines. Moreover, all the test compounds exhibited potent cytotoxic activity in nanomolar to micromolar range with IC50 values ranging from 0.58 to 8.32µM. Compound 2a showed significant cytotoxic activity against CNS (SNB-75), lung (NCI-H460) and ovarian (OVCAR-4) cancer cell lines with IC50 values 0.64, 0.78 and 1.9µM, respectively. Compound 4 showed promising potency against leukemia (HL-60) and CNS (SNB-75) cell lines (IC50 = 0.58 and 0.94µM, sequentially). Moreover, the antiproliferative activities of compounds 2a and 4 appeared to correlate well with their ability to inhibit CDK2 at sub-micromolar level (IC50 = 0.69 and 0.67µM, respectively) that were comparable to roscovitine (IC50=0.44µM). The Molecular docking results revealed that compound 4 interacted with the same key amino acids as roscovitine in the active site of CDK2 enzyme with a marked docking score (-14.1031 kcal/mol). CONCLUSION: 1-(4-Flourophenyl)pyrazolo[3,4-d]pyrimidine is a promising scaffold for the design and synthesis of potent cytotoxic leads.


Assuntos
Antineoplásicos/farmacologia , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Citotoxinas/farmacologia , Desenho de Fármacos , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/metabolismo , Citotoxinas/síntese química , Citotoxinas/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade
12.
J Enzyme Inhib Med Chem ; 34(1): 532-546, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30688116

RESUMO

A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC50 = 1.74 µM. It also exhibited promising potent anticancer activity against ACHN cell line with IC50 value 5.53 µM, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC50 = 4.44 µM) was 1.9-fold more potent than Erlotinib. It inhibited EGFR and ErbB2 kinases at sub-micromolar level (IC50 = 0.18 and 0.25 µM, respectively). Dual inhibition of EGFR and ErbB2 caused induction of apoptosis which was confirmed by a significant increase in the level of active caspase-3 (11-fold). It showed accumulation of cells in pre-G1 phase and cell cycle arrest at G2/M phase.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirazóis/síntese química , Pirazóis/química , Pirimidinas/síntese química , Pirimidinas/química , Receptor ErbB-2/metabolismo , Relação Estrutura-Atividade , Células Tumorais Cultivadas
13.
Bioorg Chem ; 83: 47-54, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30342385

RESUMO

New pyrazoles and pyrazolo[3,4-b] pyridines were synthesized and their structure was confirmed by elemental analyses as well as IR, 1H NMR, 13C NMR, and mass spectral data. All the newly synthesized derivatives were evaluated in vitro for inhibitory activity against COX-1 and COX-2 enzymes and their IC50 values were calculated, most of the derivatives showed good inhibitory activity with derivatives IVb, IVh and IVJ showing inhibitory activity better than celecoxib. Moreover, the eight most potent derivatives IVa, IVb, IVc, IVd, IVe, IVh, IVJ, and IVL were selected for in vivo assay to measure their effect on paw edema in rates and their ulcerogenic effect. Compounds IVa, IVb and IVc were found to be the most active and selective as COX-2 inhibitors and most effective in protection from edema, they were also found to have lowest ulcerogenic effect among all derivatives.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Edema/tratamento farmacológico , Pirazóis/farmacologia , Piridinas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/metabolismo , Masculino , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Piridinas/síntese química , Piridinas/química , Ratos , Relação Estrutura-Atividade , Úlcera/tratamento farmacológico
14.
Therap Adv Gastroenterol ; 9(5): 684-91, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27582881

RESUMO

BACKGROUND: Minimal hepatic encephalopathy (MHE) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy. There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy. The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose. METHODS: Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests, including number connection test part A (NCT-A), digit symbol test (DST) and block design tests (BDTs). Patients were randomized to receive 175 mg zinc gluconate, 50,000 IU vitamin A, 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose, dose 30-60 ml/day for 3 months [group A (n = 31)] or initiated and maintained on lactulose dose 30-60 ml/day for 3 months [group B (n = 27)]. Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy. RESULTS: Compared with the baseline neuropsychometric tests, a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy (group A) versus patients with lactulose therapy (group B) (NCT-A, p <0.001; DST, p = 0.006; BDT, p < 0.001). Antioxidant and zinc supplementation significantly decreased arterial ammonia level, alanine aminotransferase (ALT), aspartate aminotransferase (AST) (p < 0.001) and improved Child-Pugh score in MHE after 3 months of therapy (p= 0.024). CONCLUSION: Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis.

15.
J Enzyme Inhib Med Chem ; 31(sup4): 145-153, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27590401

RESUMO

Three series of benzothiophene derivatives were designed and synthesized as cytotoxic agents. The compounds were subjected to in vitro antitumor screening at the National Cancer Institute (NCI), Bethesda, MD. The results of the single dose screening indicated that only the benzothieno[3,2-b]pyran series 3a-f exhibited potent and broad spectrum cytotoxic activity and was subjected to five dose cytotoxic screening. The most active compound in this study was 2-amino-6-bromo-4-(4-nitrophenyl)-4H-[1]benzothieno[3,2-b]pyran-3-carbonitrile (3e) with MG-MID GI50, TGI, and LC50 values of 0.11, 7.94 and 42.66 µM, respectively. Compound 3e exhibited broad spectrum anticancer activity against a panel of 59 cell lines. To elucidate the underlying mechanism of compound 3e cytotoxic activity, we examined its effect on cell cycle progression and its ability to induce apoptosis using human colon adenocarcinoma cell line (HCT-116). The effect of compound 3e on the cell cycle progression indicated that exposure of HCT-116 cells to compound 3e for 24 and 48 h, induced a significant disruption in the cell cycle profile including time dependent decrease in cell population at G1 phase with concomitant increase in pre-G and G2/M cell population. Moreover, compound 3e induced time dependent increase in the percentage of early and late apoptotic and necrotic cell population. In conclusion, we were able to successfully design a new series of benzothieno[3,2-b]pyran derivatives with potent cytotoxic activity and their mechanism of cytotoxicity was examined.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Ciclo Celular/efeitos dos fármacos , Tiofenos/química , Tiofenos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzopiranos/síntese química , Benzopiranos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tiofenos/síntese química
16.
Nat Sci Sleep ; 6: 37-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24648781

RESUMO

BACKGROUND: Children with nocturnal enuresis (NE) are believed to have deep sleep with high arousal threshold. Studies suggest that obstructive sleep apnea-hypopnea syndrome (OSAHS) and NE are common problems during childhood. We sought to assess the prevalence of OSAHS in children with refractory NE and whether its severity is associated with the frequency of bedwetting. METHODS: The study group comprised 43 children with refractory monosymptomatic NE and a control group of 30 children, both aged 6-12 years. All subjects underwent thorough neurological examination, one night of polysomnography only for the patient group, and a lumbosacral plain X-ray to exclude spina bifida. RESULTS: The groups were well matched. Two subjects of the control group had mild OSAHS. The mean age of the patients was (9.19±2.4 years), 26 were boys, and 67% showed frequent NE (>3 days bedwetting/week). Patients with NE had significantly higher rates of OSAHS (P<0.0001); three patients had mild, 12 had moderate, and eleven showed severe OSAHS. There was no significant statistical difference among patients having OSAHS in relation to age, sex, or family history of NE. The frequency of bedwetting was statistically significantly higher in patients with severe OSAHS (P=0.003). CONCLUSION: Patients with refractory NE had a significantly higher prevalence of OSAHS with no sex difference. The frequency of bedwetting was higher in patients with severe OSAHS.

17.
Arab J Gastroenterol ; 12(2): 58-61, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21684474

RESUMO

BACKGROUND AND STUDY AIMS: Minimal hepatic encephalopathy (MHE) represents a part of the spectrum of hepatic encephalopathy (HE). It can have a far-reaching impact on quality and ability to function in daily life and may progress to overt HE. This study was designed to screen for MHE in drivers with liver cirrhosis in Mansoura, a city in the Nile delta in Egypt. PATIENTS AND METHODS: A total of 174 consecutive drivers with positive serology for viral markers and cirrhosis were screened for MHE. Questionnaires and standard psychometric tests and well-informed consent were performed at the same setting. The diagnosis of MHE was made when one or both symbol digit test (SDT) and number connection test (NCT) appeared abnormal. Beck's inventory and Mini Mental State Examination questionnaires were performed for those diagnosed as MHE. After overnight fasting, venous blood samples were taken for haematologic tests and routine liver function tests by conventional methods. Arterial ammonia was also measured. RESULTS: A total of 66 patients showed evidence for MHE out of 139 patients who fulfilled the inclusion criteria. No significant differences were present, apart from a significantly elevated arterial ammonia level (p-value <0.001) and a bad self-reported driving history (p<0.05) in the MHE-positive group when compared with the MHE-negative group. Multivariate logistic regression revealed that advanced Child-Pugh grade (p<0.001), hepatitis B virus (HBV)-related aetiology (p<0.001) and smoking are significant risk factors for MHE. MHE is significantly commoner among Child-Pugh C patients (p<0.05) when compared with the other Child-Pugh grades. CONCLUSION: Our data revealed a high prevalence of MHE (47%) among Egyptian drivers with liver cirrhosis. It is hence recommended to include the driving history as well as regular pencil-paper standard psychometric testing in evaluating those at risk, especially in the outpatient setting, for early detection and proper management.


Assuntos
Condução de Veículo , Encefalopatia Hepática/epidemiologia , Cirrose Hepática/complicações , Adulto , Egito/epidemiologia , Encefalopatia Hepática/etiologia , Hepatite B/complicações , Humanos , Modelos Logísticos , Programas de Rastreamento , Pessoa de Meia-Idade , Psicometria , Fumar , Inquéritos e Questionários , Adulto Jovem
18.
Ann Indian Acad Neurol ; 12(3): 173-8, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20174498

RESUMO

BACKGROUND: The neurovascular conflict in trigeminal neuralgia is an intractable condition; medical treatment is usually of long duration and can be annoying for both patients and clinicians. AIM: This prospective study was designed to assess the outcome of microvascular decompression (MVD) in patients with more than 3 years' history of intractable idiopathic trigeminal neuralgia (TN) and poor response to drugs. MATERIALS AND METHODS: Twenty-one patients (8 females and 13 males) with intractable idiopathic TN (group 1) underwent MVD and were followed up for 2 years. Group 2 (n = 15), which included 6 females and 9 males, received pharmacotherapy. The outcome responses of pain relief were evaluated using a 10-cm visual analog scale (VAS) and the Barrow Neurological Institute (BNI) scoring system. The patients' morbidity was recorded as well. RESULTS: All patients fulfilling the inclusion criteria were offered MVD surgery. Freedom from pain was achieved immediately after surgery in 95.2% (n = 20) of patients in group 1, and 90.5% (n = 19) had sustained relief over the follow-up period. There were no statistical significance recurrences or surgical complications in group 1 (P>0.5), while 53.3% (n = 8) of the subjects in group 2 showed poor response with pharmacotherapy over the same period of time and many patients experienced drug intolerance that had statistical significance (P<0.01). CONCLUSION: Early MVD in TN can help patients avoid the side effects of drugs and the adverse psychological effects of long-term pharmacotherapy and prolonged morbidity.

19.
Chaos ; 18(2): 023114, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18601481

RESUMO

A simple technique is introduced to build fast state observers for chaotic systems when only a scalar time series of the output is available. This technique relies on using a backstepping-like approach via introducing new virtual states that can be observed using the drive-response synchronization mechanism. The proposed dynamic structure of the virtual states allows for employing control parameters that can adjust the convergence rate of the observed states. In addition, these control parameters can be used to improve the transient performance of the response system to accommodate small and large variations of the initial conditions, thus achieving superior performance to conventional synchronization techniques. Simple Lyapunov functions are used to estimate the range of the control parameters that guarantees stable operation of the proposed technique. Three benchmark chaotic systems are considered for illustration; namely, the Lorenz, Chua, and Rossler systems. The conflict between stability and agility of the states observer is analyzed and a simple tuning mechanism is introduced. Implementation of the proposed technique in both analog and digital forms is also addressed and experimental results are reported ensuring feasibility and real-time applicability. Finally, advantages and limitations are discussed and a comparison with conventional synchronization methods is investigated.


Assuntos
Dinâmica não Linear , Oscilometria/métodos , Algoritmos , Simulação por Computador , Desenho de Equipamento , Modelos Teóricos , Oscilometria/instrumentação , Física/métodos , Processamento de Sinais Assistido por Computador , Software , Teoria de Sistemas
20.
Phys Rev E Stat Nonlin Soft Matter Phys ; 77(3 Pt 2): 036212, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18517490

RESUMO

A technique is introduced for identifying uncertain and/or unknown parameters of chaotic dynamical systems via using simple state feedback. The proposed technique is based on bringing the system into a stable steady state and then solving for the unknown parameters using a simple algebraic method that requires access to the complete or partial states of the system depending on the dynamical model of the chaotic system. The choice of the state feedback is optimized in terms of practicality and causality via employing a single feedback signal and tuning the feedback gain to ensure both stability and identifiability. The case when only a single scalar time series of one of the states is available is also considered and it is demonstrated that a synchronization-based state observer can be augmented to the state feedback to address this problem. A detailed case study using the Lorenz system is used to exemplify the suggested technique. In addition, both the Rössler and Chua systems are examined as possible candidates for utilizing the proposed methodology when partial identification of the unknown parameters is considered. Finally, the dependence of the proposed technique on the structure of the chaotic dynamical model and the operating conditions is discussed and its advantages and limitations are highlighted via comparing it with other methods reported in the literature.

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