RESUMEN
The objective of this study was to compare the level of total antioxidant status (TAS) in type 2 diabetic and normal Palestinian subjects as well as the major factors influencing TAS levels. A sample of convenience composed of 212 type 2 diabetic and 208 normal subjects above the age of 40 were recruited. Only 9.8% of the subjects had normal body mass index (BMI) levels (<25), 29% were overweight (≥25 to <30), and 61.2% were obese (≥30). The mean levels of TAS were significantly higher in diabetic compared to control subjects (2.18 versus 1.84 mM Trolox, P = 0.001) and in hypertensive subjects compared to subjects with normal blood pressure (BP). Mean TAS levels were higher in obese compared to nonobese subjects (2.12 versus 1.85 mM Trolox, P = 0.001). Mean TAS levels were similarly higher in subjects with high fasting plasma glucose (FPG) compared to normal FPG (2.19 versus 1.90 mM Trolox) and high HbA1c (≥6.5%) compared to HbA1c < 6.5% (2.14 versus 1.91 mM Trolox). Multivariate analysis revealed that only diabetic status (P = 0.032) and the level of education (P = 0.036) were significantly associated with TAS. In conclusion diabetic patients had 18.5% increase in TAS levels compared to control subjects.
Asunto(s)
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hiperglucemia/prevención & control , Estado Nutricional , Estrés Oxidativo , Árabes , Glucemia/análisis , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/etnología , Escolaridad , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Hipertensión/etnología , Hipoglucemiantes/uso terapéutico , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Medio Oriente/epidemiología , Estado Nutricional/etnología , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/etnología , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Sobrepeso/etnología , Estrés Oxidativo/efectos de los fármacosRESUMEN
A series of novel Zn(II) complexes [Zn2(nap)4] (1), [Zn(nap)21,10-phen](2), [Zn(nap)22,9-dmphen] (3), [Zn(nap)2(2-ampy)2] (4), [Zn(nap)2(imid)2] (5), [Zn(nap)2(1,2-dmimid)2] (6) (nap = naproxen, 1,10-phen = 1,10-phenanthroline, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, 2-ampy = 2-aminopyridine, imid = imidazole, 1,2-dmimid = 1,2-dimethyl imidazole) were synthesized and characterized using IR, UV-Vis, (1)H NMR, (13)C{(1)H} NMR spectroscopy. The crystal structure of complex 3 was determined using single-crystal X-ray diffraction. In order to assess the effect of the metal ions on the anti-bacterial activity, complexes 1-6 have been screened in vitro, against (G(+)) bacteria (Staphylococcus aureus and Micrococcus luteus) and (G(-)) bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Escherichia coli) using the agar well diffusion method. Complex 2 was the only complex that showed antibacterial activity against P. aeruginosa, where the complexation of the parent ligand 1,10-phenathroline enhanced significantly the activity. All the complexes showed different activity against the different bacteria, and were compared with activity of the parent ligands. The complexes were tested also for their anti-malarial activity using two methods: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment. This is considered an important target of many known anti-malarial drugs such as Chloroquine and Amodaquine. Results showed that the efficiency of complex 3 in preventing the formation of ß-hematin was 75%. The efficiency of Amodiaquine as a standard drug was reported to give 92.5.
Asunto(s)
Antibacterianos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Naproxeno/farmacología , Nitrógeno/química , Compuestos Organometálicos/farmacología , Zinc/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antimaláricos/síntesis química , Antimaláricos/química , Antimaláricos/farmacología , Relación Dosis-Respuesta a Droga , Ligandos , Malaria/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Naproxeno/química , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-Actividad , Zinc/químicaRESUMEN
Starting from the precursor [Zinc Valproate complex] (1), new mixed ligand zinc(II) complexes of valproic acid and nitrogen-based ligands, formulating as, [Zn(valp)22,9-dmphen] (2), [Zn2(valp)4(quin)2] (3), [Zn(valp)2(2-ampy)2] (4), and [Zn(valp)2(2-ampic)2] (5) (valp = valproate, 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline, quin = quinoline, 2-ampy = 2-aminopyridine, 2-ampic = 2-amino-6-picoline) were synthesized and characterized using IR, (1)H NMR, (13)C{(1)H} NMR and UV-Vis spectrometry. The crystal structures of complexes 2, 3 and 4 were determined using single-crystal X-ray diffraction. The complexes were also evaluated for their anti-bacterial activity using in-vitro agar diffusion method against three Gram-positive (Micrococcus luteus, Staphylococcus aureus, and Bacillus subtilis) and three Gram-negative (Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis) species. Complex 2 showed considerable activity against all tested microorganisms and the effect of complexation on the anti-bacterial activity of the parent ligand of 2 was also investigated. The anti-bacterial activity of 2,9-dmphen against Gram-negative bacteria was enhanced upon complexation with zinc valproate. On the other hand, complexes 1 and 3 showed weak inhibition activity against the tested species and complexes 4 and 5 didn't show any activity at all. Two methods were used for testing the inhibition of ferriprotoporphyrinIX bio-mineralization: a semi-quantitative micro-assay and a previously self-developed quantitative in-vitro method. Both were used to study the efficiency of these complexes in inhibiting the formation of the Malaria pigment which considered being the target of many known anti-malarial drugs such as Chloroquine and Amodiaquine. Results showed that the efficiency of complex 2 in preventing the formation of ß-Hematin was 80%. The efficiency of Amodiaquine as a standard drug was reported to give 91%.
Asunto(s)
Antibacterianos/farmacología , Anticonvulsivantes/farmacología , Antimaláricos/farmacología , Bacterias/efectos de los fármacos , Hemoproteínas/antagonistas & inhibidores , Compuestos Organometálicos/farmacología , Ácido Valproico/farmacología , Aminopiridinas/química , Antibacterianos/síntesis química , Antibacterianos/química , Anticonvulsivantes/síntesis química , Anticonvulsivantes/química , Antimaláricos/síntesis química , Antimaláricos/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ligandos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Fenantrolinas/química , Picolinas/química , Quinolinas/química , Relación Estructura-Actividad , Ácido Valproico/síntesis química , Ácido Valproico/química , Zinc/químicaRESUMEN
Solving structures of membrane proteins has always been a formidable challenge, yet even upon success, the results are normally obtained in a mimetic environment that can be substantially different from a biological membrane. Herein, we use noninvasive isotope-edited FTIR spectroscopy to derive a structural model for the SARS coronavirus E protein transmembrane domain in lipid bilayers. Molecular-dynamics-based structural refinement, incorporating the IR-derived orientational restraints points to the formation of a helical hairpin structure. Disulfide cross-linking and X-ray reflectivity depth profiling provide independent support of the results. The unusually short helical hairpin structure of the protein might explain its ability to deform bilayers and is reminiscent of other peptides with membrane disrupting functionalities. Taken together, we show that isotope-edited FTIR is a powerful tool to analyze small membrane proteins in their native environment, enabling us to relate the unusual structure of the SARS E protein to its function.
RESUMEN
Background: Malaria is a devastating disease, particularly in Africa, due to development of resistance by Plasmodium falciparum against all known antimalarial drugs, including artemisinin. Therefore, the search for new antimalarial drugs is urgently needed, especially drugs that can impede the heme detoxification pathway in the malaria parasite, a crucial requirement for parasite survival in host erythrocytes. Materials and Methods: Water infusions of Artemisia annua plants from two different origins, Cameroon and Luxembourg, were used in this study. A semi-quantitative in vitro method, based on the inhibition of ferriprotoporphyrin IX (FP) biomineralisation developed by Deharo et al. [16], was used to reveal the differences in antimalarial activity of both plants. Reversed phase preparative liquid chromatography coupled to a photo diode array (PDA) detector was also used to test for differences in antimalarial activity. Results: Water extracts from the leaves of the Cameroon plant showed a higher potential antimalarial activity, represented by a higher ability to inhibit ß-haematin formation in vitro than A. annua extracts from Luxembourg. Although extracts of the plants of both origins showed comparable efficiencies at high concentrations, the absorbance value at 405 nm of a 10% dilution of the Cameroon plant extract was 0.075, whereas it was 1.515 for the Luxembourg plant extract. The absorbance is inversely proportional to the antimalarial activity. According to the Prep-HPLC chromatogram of the Cameroon crude sample, seven major compounds at 325 nm were found. However, only four much less pronounced compounds appeared in the Luxembourg crude sample under the same chromatographic conditions and concentration. These were preliminarily identified as polyphenolic compounds. Conclusion: A. annua infusions are widely used by people who cannot afford other treatments. Depending on the cultivation locality different chemical profiles exist. This results in differences in hemozoin formation and will therefore also lead to alterations in antimalarial activity.
RESUMEN
BACKGROUND: The highly upregulated in liver cancer (HULC) gene transcribes to an mRNA-like noncoding RNA (ncRNA) by the RNA polymerase II and processed by capping, splicing and polyadenylation. It is specifically expressed in the hepatocytes with striking upregulation in hepatocellular carcinoma (HCC). OBJECTIVES: To study the expression levels of HULC in normal colorectal samples, primary colorectal carcinomas and in secondary tumors formed from colorectal carcinomas that metastasize to either the liver or the lymph nodes, taken from the same patients. Also a panel of carcinoma cell lines is tested for HULC expression. BASIC METHODS: Semiquantitative reverse transcriptase-PCR technique is used to detect for HULC expression in study specimens and cell lines. RESULTS: Consistent with the previous report, HULC is neither expressed in primary colorectal carcinomas samples nor in their normal counterparts. We show for the first time those colorectal carcinomas that metastasize to the livers but not to lymph nodes experience an upregulation of HULC ncRNA in all the samples tested (n= 8), with a strong-to-moderate expression in six out of eight. Moreover HULC is not expressed in the majority of carcinoma cell lines tested and also in samples of normal bladder and bladder cancers of various grades. We also show that HULC ncRNA is upregulated in two hepatocellular carcinoma cell lines producing HBV relevant to their parental lines that do not produce HBV. CONCLUSION: Our results presented here indicate that HULC expression is not confined to HCC, but also to those colorectal carcinomas that metastasize to the liver.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Hepáticas/genética , ARN Neoplásico/genética , ARN no Traducido/genética , Regulación hacia Arriba , Animales , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/secundario , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
The agent responsible for the recent severe acute respiratory syndrome (SARS) outbreak is a previously unidentified coronavirus. While there is a wealth of epidemiological studies, little if any molecular characterization of SARS coronavirus (SCoV) proteins has been carried out. Here we describe the molecular characterization of SCoV E protein, a critical component of the virus responsible for virion envelope morphogenesis. We conclusively show that SCoV E protein contains an unusually short, palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature which seems to be unique to SCoV. The hairpin deforms lipid bilayers by way of increasing their curvature, providing for the first time a molecular explanation of E protein's pivotal role in viral budding. The molecular understanding of this critical component of SCoV may represent the beginning of a concerted effort aimed at inhibiting its function, and consequently, viral infectivity.