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Ramadan fasting (RF) involves abstaining from food and drink during daylight hours; it is obligatory for all healthy Muslims from the age of puberty. Although sick individuals are exempt from fasting, many will fast anyway. This article explores the impact of RF on individuals with kidney diseases through a comprehensive review of existing literature and consensus recommendations. This study was conducted by a multidisciplinary panel of experts.The recommendations aim to provide a structured approach to assess and manage fasting during Ramadan for patients with kidney diseases, empowering both healthcare providers and patients to make informed decisions while considering their unique circumstances.
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Nefropatias , Humanos , Consenso , Pacientes , Pessoal de Saúde , JejumRESUMO
BACKGROUND: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial. PATIENTS AND METHODS: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients. RESULTS: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: -3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (-7.4 and -8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570. CONCLUSION: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years.
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Neoplasias do Sistema Nervoso Central , Qualidade de Vida , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Nível de Saúde , Humanos , Rituximab , Inquéritos e QuestionáriosRESUMO
PURPOSE: Evidence from industrialized/developed countries showed that colorectal cancer (CRC) incidence rates have significantly dropped due to the widespread use of colonoscopy. In Arab countries, however, the CRC had been reported to have increased. Despite the concerted effort in the primary prevention and widespread use of colonoscopy, to our knowledge, there have been no reports of the prevalence rate of CRC among colonoscopy recipients from Oman. This study aims to explore the CRC prevalence estimates over selected sociodemographic characteristics among colonoscopy-recipients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. METHODS: This hospital-based cross-sectional study reviewed reports of colonoscopies performed over 5-years of retrospective follow-up at a tertiary hospital in Oman. CRC prevalence estimates were calculated over age, gender, governorate, and time of follow-up. RESULTS: A total of 442 CRC cases were enumerated among 3701 colonoscopies, with an overall CRC prevalence estimate of 11.9 per 100 colonoscopies (95% CI: 10.9, 13.0). Gender-specific CRC prevalence was higher among males compared with females (13.3 vs. 10.5). Age-specific CRC prevalence increased with advancing age, from 2.8 among those less than 40 years of age to 26.5 among aged 70 years or more. Regional CRC prevalence was highest among residents in Batinah Governorate. Over the 5-years of follow-up, there was a slow rise in CRC prevalence with an annual increment of 0.59%. CONCLUSION: The study provides supportive evidence for a steady increase in CRC prevalence over age categories and years of follow-up and depicted the variations of gender-specific CRC prevalence estimates over increasing age categories. The study calls for timely formulation and adoption of national CRC screening programs centered on the colonoscopy use as primary prevention and maximizing its utilization and efficiency.
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Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Centros de Atenção Terciária , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/história , Estudos Transversais , Detecção Precoce de Câncer , Feminino , História do Século XXI , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Omã/epidemiologia , Prevalência , Vigilância em Saúde Pública , Estudos RetrospectivosRESUMO
The scope for biocatalytic modification of non-native carvone derivatives for speciality intermediates has hitherto been limited. Additionally, caprolactones are important feedstocks with diverse applications in the polymer industry and new non-native terpenone-derived biocatalytic caprolactone syntheses are thus of potential value for industrial biocatalytic materials applications. Biocatalytic reduction of synthetic analogues of R-(-)-carvone with additional substituents at C3 or C6, or both C3 and C6, using three types of OYEs (OYE2, PETNR and OYE3) shows significant impact of both regio-substitution and the substrate diastereomer. Bioreduction of (-)-carvone derivatives substituted with a Me and/or OH group at C6 is highly dependent on the diastereomer of the substrate. Derivatives bearing C6 substituents larger than methyl moieties are not substrates. Computer docking studies of PETNR with both (6S)-Me and (6R)-Me substituted (-)-carvone provides a model consistent with the outcomes of bioconversion. The products of bioreduction were efficiently biotransformed by the Baeyer-Villiger monooxygenase (BVase) CHMO_Phi1 to afford novel trisubstituted lactones with complete regioselectivity to provide a new biocatalytic entry to these chiral caprolactones. This provides both new non-native polymerization feedstock chemicals, but also with enhanced efficiency and selectivity over native (+)-dihydrocarvone Baeyer-Villigerase expansion. Optimum enzymatic reactions were scaled up to 60-100â mg, demonstrating the utility for preparative biocatalytic synthesis of both new synthetic scaffold-modified dihydrocarvones and efficient biocatalytic entry to new chiral caprolactones, which are potential single-isomer chiral polymer feedstocks.
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Caproatos/metabolismo , Lactonas/metabolismo , Oxigenases de Função Mista/metabolismo , Monoterpenos/metabolismo , Oxirredutases/metabolismo , Rhodococcus/enzimologia , Saccharomyces cerevisiae/enzimologia , Biocatálise , Biotransformação , Caproatos/química , Monoterpenos Cicloexânicos , Microbiologia Industrial , Lactonas/química , Modelos Moleculares , Monoterpenos/química , Oxirredução , Rhodococcus/química , Rhodococcus/metabolismo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , EstereoisomerismoRESUMO
In healthy or pathological brains, the neuroinflammatory state is supported by a strong communication involving microglia and neurons. Recent studies indicate that extracellular vesicles (EVs), including exosomes and microvesicles, play a key role in the physiological interactions between cells allowing central nervous system (CNS) development and/or integrity. The present report used medicinal leech CNS to investigate microglia/neuron crosstalk from ex vivo approaches as well as primary cultures. The results demonstrated a large production of exosomes from microglia. Their incubation to primary neuronal cultures showed a strong interaction with neurites. In addition, neurite outgrowth assays demonstrated microglia exosomes to exhibit significant neurotrophic activities using at least a Transforming Growth Factor beta (TGF-ß) family member, called nGDF (nervous Growth/Differentiation Factor). Of interest, the results also showed an EV-mediated dialog between leech microglia and rat cells highlighting this communication to be more a matter of molecules than of species. Taken together, the present report brings a new insight into the microglia/neuron crosstalk in CNS and would help deciphering the molecular evolution of such a cell communication in brain.
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Sistema Nervoso Central/metabolismo , Exossomos/metabolismo , Hirudo medicinalis/fisiologia , Microglia/metabolismo , Neurônios/metabolismo , Sequência de Aminoácidos , Animais , Sistema Nervoso Central/efeitos dos fármacos , Técnicas de Cocultura , Exossomos/efeitos dos fármacos , Exossomos/ultraestrutura , Microglia/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Neuritos/efeitos dos fármacos , Neuritos/metabolismo , Neurônios/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 µg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 µg/l [2.6;4.9], P = 0.05) and controls (3.8 µg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti-CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes.
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Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/metabolismo , Osso e Ossos/metabolismo , Galectina 3/metabolismo , Membrana Sinovial/metabolismo , Adolescente , Adulto , Idoso , Animais , Artrite Reumatoide/imunologia , Proteínas Sanguíneas , Reabsorção Óssea , Osso e Ossos/patologia , Progressão da Doença , Feminino , Fibrose , Seguimentos , Galectinas , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/patologia , Adulto JovemRESUMO
Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our objectives were to study whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to exercise in RA and controls. The study on circadian patterns (1) comprised eleven patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10 patients with long-standing RA [5-15 years (LRA)] and 16 self-reportedly healthy control subjects. During 24 h, 7 blood samples were drawn at 3-h intervals starting at 10 a.m. through 10 p.m. and at 7 and 10 a.m. on the following day. The study on the effect of physical activity (2) included 10 patients with ERA, 10 with LRA and 14 controls. The participants underwent a standardized exercise programme and four blood samples were drawn before, during and after exercise. Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was increased at baseline in both RA subsets (P = 0.08). There were no diurnal oscillations (P = 0.85). Day-to-day variation amounted to 3%. (2) Baseline Galectin-3 was increased in LRA versus controls and ERA (P < 0.01 and 0.05). Physical exercise induced 10-15% Galectin-3 increments in RA and controls (P < 0.001) peaking after 1-3 h. To conclude, Galectin-3 did not exhibit circadian variation. Day-to-day variation was 3%. Exercise elicited comparable increments in patients with RA of short and long duration and controls, approaching normal after 1-3 h.
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Artrite Reumatoide/sangue , Ritmo Circadiano , Exercício Físico , Galectina 3/sangue , Mediadores da Inflamação/sangue , Adulto , Idoso , Proteínas Sanguíneas , Feminino , Galectinas , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: While there has been significant progress in outcomes for patients diagnosed with primary central nervous system (CNS) lymphoma (PCNSL), survival rates will likely plateau with the current armamentarium of agents used to treat these patients. Moreover, given that PCNSL increasingly impacts an older population, a significant proportion of patients are not eligible for intensive therapies such as high-dose chemotherapy or whole-brain radiation. There is a need for the development of novel agents, which target key survival pathways in order to continue to make progress in this disease. PATIENTS AND METHODS: We reviewed the key molecular pathways and genomic aberrations in PCNSL in order to identify candidate targets. We focused on molecules and pathways that have been identified and confirmed by more than one investigator or methodology. RESULTS: While PCNSL tumors usually express a BCL6+, MUM1+ 'activated, germinal center' immunophenotype, they exhibit multiple shared genetic properties with ABC-type diffuse large B-cell lymphomas. Candidate targets and pathways include NFkB, the B-cell receptor, the JAK/STAT pathway, IRF4, BCL-6 as well as PIM kinases. Elements of the tumor microenvironment that may be exploited therapeutically include chemokine pathways, as well as macrophage and T-cell responses. CONCLUSIONS: There is a significant need for developing novel therapies in PCNSL, given that an increasing proportion of patients are not eligible for high-dose chemotherapy and brain radiation is associated with detrimental cognitive side-effects. We provide an overview of potential drug targets and novel agents that may be integrated with existing strategies in order to make further progress in this disease.
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Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Metotrexato/administração & dosagem , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/patologia , Quimiorradioterapia , Humanos , Linfoma/metabolismo , Linfoma/patologia , Fenótipo , Microambiente TumoralRESUMO
ß-Thalassemia (ß-thal) is a public health problem in the Gaza Strip, Palestine, where about 320 patients are currently managed through blood transfusions and iron chelation. Within the restrictive environment of the Gaza Strip, no advanced molecular analysis [sequencing, real-time polymerase chain reaction (real-time PCR)] technology is currently available for developing a premarital screening protocol and providing couples at risk with prenatal diagnosis. Therefore, genetic identification of samples with indicators of ß-thal is delayed for weeks before the samples can be sequenced outside the country. As nine causative mutations have been identified in the majority of ß-thal cases in the Gaza Strip, a basic genetic screening strategy was designed to improve timeliness in mutation identification and reduce costs to the Palestinian health system. In the present study, we developed a reliable method for the detection of nine Mediterranean ß-thal mutations common to the Palestinian population using a panel of restriction enzyme digests. This strategy utilizes standard instrumentation (thermocycler and agarose gel electrophoresis) that would be available in any basic molecular genetics or biochemical laboratory and provides a reliable method of genetic screening and counseling for patients at risk for ß-thal.
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Análise do Polimorfismo de Comprimento de Fragmentos Amplificados/métodos , Árabes/genética , Mutação , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Enzimas de Restrição do DNA , Países em Desenvolvimento , Humanos , Reprodutibilidade dos TestesRESUMO
Single-molecule experimental methods have provided new insights into biomolecular function, dynamic disorder, and transient states that are all invisible to conventional measurements. A novel, nonfluorescent single-molecule technique involves attaching single molecules to single-walled carbon nanotube field-effective transistors (SWNT FETs). These ultrasensitive electronic devices provide long-duration, label-free monitoring of biomolecules and their dynamic motions. However, generalization of the SWNT FET technique first requires design rules that can predict the success and applicability of these devices. Here, we report on the transduction mechanism linking enzymatic processivity to electrical signal generation by a SWNT FET. The interaction between SWNT FETs and the enzyme lysozyme was systematically dissected using eight different lysozyme variants synthesized by protein engineering. The data prove that effective signal generation can be accomplished using a single charged amino acid, when appropriately located, providing a foundation to widely apply SWNT FET sensitivity to other biomolecular systems.
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Muramidase/química , Muramidase/metabolismo , Nanotubos de Carbono/química , Engenharia de Proteínas , Transdução de Sinais , Modelos Moleculares , Transistores EletrônicosRESUMO
Single-molecule studies of enzymes open a window into their dynamics and kinetics. A single molecule of the catalytic domain of cAMP-dependent protein kinase A (PKA) was attached to a single-walled carbon nanotube device for long-duration monitoring. The electronic recording clearly resolves substrate binding, ATP binding, and cooperative formation of PKA's catalytically functional, ternary complex. Using recordings of a single PKA molecule extending over 10 min and tens of thousands of binding events, we determine the full transition probability matrix and conversion rates governing formation of the apo, intermediate, and closed enzyme configurations. We also observe kinetic rates varying over 2 orders of magnitude from one second to another. Anti-correlation of the on and off rates for PKA binding to the peptide substrate, but not ATP, demonstrates that regulation of enzyme activity results from altering the stability of the PKA-substrate complex, not its binding to ATP. The results depict a highly dynamic enzyme offering dramatic possibilities for regulated activity, an attribute useful for an enzyme with crucial roles in cell signaling.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Trifosfato de Adenosina/metabolismo , Catálise , Cinética , Nanotubos de CarbonoRESUMO
BACKGROUND: ß-Thalassemia is a disorder caused by mutations at the hemoglobin ß-gene (HBB) locus. Its most important manifestation, the major form, is characterized by severe hypochromic and hemolytic anemia and is inherited in an autosomal recessive mode. In Gaza Strip, Palestine 0.02% of the population has been identified as ß-thalassemia major. DESIGN AND METHODS: An assessment of mutations was performed in 49 transfusion dependent patients with ß-thalassemia major and in 176 ß-thalassemia carriers diagnosed with a mean erythrocyte cell volume (MCV) <80fl and a proportion of HbA2>3.5%. In addition 39 individuals suspicious for ß-thalassemia carrier status due to a reduced MCV (<80fl) but a normal HBA2 were screened. RESULTS: By screening with three hybridization assays a proportion of 80% of the thalassemic chromosomes from patients and carriers was identified to carry five different mutations of the hemoglobin (Hb) ß-gene. Subsequent DNA sequencing confirmed these and revealed further 9% of the chromosomes to be affected by other mutations. In addition six chromosomes from suspicious carriers were detected to carry ß-thalassemia mutations. Of the 15 different HBB mutations identified the variant IVS-I-110 G>A was the most frequent mutation identified in 34% of the thalassemic chromosomes, followed by IVS-I-1 G>A, IVS-I-6 T>C, Codon 39 C>T, and Codon 37 G>A. Three novel HBB variants were discovered by direct sequencing of the gene: 5' UTR-50 (-/G), 5' UTR-43 C>T, and IVS-II-26 T>G. CONCLUSIONS: The spectrum of HBB mutations described is of the Mediterranean type whereby the allele frequencies of the most common mutations differ from those, which were previously described for the population of the Gaza Strip and other Palestinian populations. The data presented may promote the introduction of molecular testing to the Palestinian premarital screening program for ß-thalassemia in Gaza Strip, which will improve the screening protocol and genetic counseling in the future.
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Mutação , Globinas beta/genética , Talassemia beta/genética , Éxons , Frequência do Gene , Genótipo , Humanos , Oriente Médio/epidemiologia , Talassemia beta/epidemiologiaRESUMO
The annual testicular cycle of the house gecko Hemidactylus flaviviridis in Oman was studied. Plasma testosterone (T), estradiol (E2) and progesterone (P) concentrations were measured using a sensitive HPLC-MS/MS detection technique. The ultrastructural steroidogenic features in Sertoli and Leydig cells, which were the major source of steriodogenesis, were examined, using transmission electron microscopy (TEM). In addition, progesterone receptors (PR) were examined throughout the testicular cycle, using an immunohistochemical technique. The steroidogenic ultrastructural features were characterized by the presence of smooth endoplasmic reticulum (SER) in the form of cisternal whorls and tubular cisternae, presence of swollen vesiculated mitochondria, and association between SER, mitochondria and lipid droplets. The rise in plasma steroid concentrations was closely associated with the development of the ultrastructural features and PR expression in Leydig and Sertoli cells. During the active phase (November-May), there was a significant rise in plasma steroid concentrations (P<0.05) related to well developed steroidogenic features and strongly expressed PR. During the quiescent phase (June-August) there was a significant decline in plasma steroid concentrations, undeveloped steroiodogenic features and weakly expressed PR. The Renal Sexual Segment (RSS) was fully developed during the active phase. The data provides strong evidence that these ultrastructural steroidogenic features were related to the plasma sex steroid concentrations during the testicular cycle.
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Lagartos/sangue , Lagartos/fisiologia , Receptores de Progesterona/metabolismo , Reprodução/fisiologia , Animais , Cromatografia Líquida de Alta Pressão , Estradiol/sangue , Imuno-Histoquímica , Células Intersticiais do Testículo/ultraestrutura , Lagartos/metabolismo , Masculino , Microscopia Eletrônica de Transmissão , Omã , Progesterona/sangue , Células de Sertoli/ultraestrutura , Testosterona/sangueRESUMO
On account of the reported anticancer of pyrimidine and condensed pyrimidine, a new pyrimido [3,2-b]-1,2,4,5-tetrazine 3a , b , 5c , d , 6, 9, pyrimido [3,2-b]-1,2,4-triazine 10, 11, pyrimido [3,2-b]-1,2,4-triazole 12 and pyrimidine derivatives 1,2a , b , 4c , d , 8, 13, 14, 15 and 16 were synthesized through different chemical reactions. Structures of all synthesized compounds were supported by spectral and elemental analyses. The obtained compounds were evaluated for their in vitro antitumor activity against human liver cancer cell line (HEPG2).
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Background and aim Becker muscular dystrophy (BMD) is an X-linked disease caused by an in-frame mutation in the dystrophin gene, which is considered an allelic disorder to the most severe form of dystrophinopahies, Duchenne muscular dystrophy, which leads to skeletal and cardiac muscle involvement and results in dilated cardiomyopathy (DCM). The aim of this study is to present our ECG data and the significance of this data in the early detection of DCM in these patients. Methods This is a retrospective study. All patients known to the clinical Genetic Clinic and Queen Alia Heart Center in Jordan with a diagnosis of Becker muscular dystrophy from the year 2011-2022 are offered cardiac evaluation according to the guidelines, which included clinical assessment, electrocardiograph, and 2-D echocardiograph (echo) at the time of diagnosis and every five years thereafter once the initial assessment was normal. All the records were retrieved and analyzed. Results Fifty-three patients of all ages with genetically confirmed BMD were identified. Twelve had no record as they didn't attend any cardiac evaluation. Forty-one were under regular clinical follow-up. Two were excluded as they died, and another four had no recorded data in our center. Ultimately, 35 patients were included and studied. The mean age was 30.5 years ± 22.1, ranging from two to seventy-seven years of age. Twenty-seven (77%) had abnormal ECG. High voltage R wave in V2 and V1 was the most common finding, followed by repolarisation abnormalities and Q wave (43%, 17%, 13%, and 11% respectively). Incomplete right bundle branch block in 4% as well as R/S ratio >1.2. U wave abnormalities in 3% and sinus tachycardia were found in only one patient. Conclusion Cardiac surveillance for patients with Becker muscular dystrophy is mandatory after the age of 16. Q wave and repolarisation changes should be taken seriously as early signs of dilated cardiomyopathy, even if the echo is normal.
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The dynamic processivity of individual T4 lysozyme molecules was monitored in the presence of either linear or cross-linked peptidoglycan substrates. Single-molecule monitoring was accomplished using a novel electronic technique in which lysozyme molecules were tethered to single-walled carbon nanotube field-effect transistors through pyrene linker molecules. The substrate-driven hinge-bending motions of lysozyme induced dynamic electronic signals in the underlying transistor, allowing long-term monitoring of the same molecule without the limitations of optical quenching or bleaching. For both substrates, lysozyme exhibited processive low turnover rates of 20-50 s(-1) and rapid (200-400 s(-1)) nonproductive motions. The latter nonproductive binding events occupied 43% of the enzyme's time in the presence of the cross-linked peptidoglycan but only 7% with the linear substrate. Furthermore, lysozyme catalyzed the hydrolysis of glycosidic bonds to the end of the linear substrate but appeared to sidestep the peptide cross-links to zigzag through the wild-type substrate.
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Simulação de Dinâmica Molecular , Muramidase/metabolismo , Peptidoglicano/biossíntese , Bacteriófago T4/enzimologia , Biocatálise , Hidrólise , Muramidase/química , Nanotubos de Carbono/química , Peptidoglicano/química , Peptidoglicano/metabolismoRESUMO
A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystallin variant, termed integrase binding protein-10 (IBP-10), inhibits integrase catalysis with nanomolar K(i) values. IBP-10 interacts with the integrase C-terminal domain and inhibits integrase substrate affinity. This allosteric mechanism allows IBP-10 to inhibit drug-resistant integrase variants. The results demonstrate the applicability of the crystallin scaffold for the discovery of binding partners and enzyme inhibitors.
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Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/metabolismo , HIV-1/enzimologia , Engenharia de Proteínas/métodos , gama-Cristalinas/farmacologia , Sequência de Aminoácidos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Integrase de HIV/química , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Modelos Moleculares , Biblioteca de Peptídeos , Ligação Proteica , Estrutura Terciária de Proteína , gama-Cristalinas/química , gama-Cristalinas/genéticaRESUMO
Dendrophthoe falcata is a hemiparasitic plant commonly used for ailments such as ulcers, asthma, impotence, paralysis, skin diseases, menstrual troubles, pulmonary tuberculosis, and wounds. In this context, the validations of the traditional claim that the leaf extract of D. falcata possesses antibiofilm and anti-quorum sensing activity against different bacterial pathogens were assessed. The bacterial biofilms were quantified by crystal violet staining. Among the 17 bacterial pathogens screened, the methanolic fraction of the leaf extract clearly demonstrated antibiofilm activity for Proteus mirabilis, Vibrio vulnificus, Aeromonas hydrophila, Shigella sonnei, Chromobacterium violaceum ATCC 12472, Vibrio parahaemolyticus, Vibrio harveyi, Vibrio alginolyticus, Vibrio cholerae, and Proteus vulgaris. At biofilm inhibitory concentrations, biofilm formation was reduced by up to 70-90â%. Furthermore, the potential quorum-sensing activity of the leaf extract was tested by agar well diffusion using Chromobacterium violaceum (ATCC 12472 & CV O26) reporter strains. The inhibition of violacein production may be due to direct or indirect interference on QS by active constituents or the interactive effect of different phytocompounds present in the extracts. This is the first report on antibiofilm and QS activity of D. falcata leaf extracts, signifying the scope for development of complementary medicine for biofilm-associated infections.
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Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Loranthaceae/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Percepção de Quorum/efeitos dos fármacos , Aeromonas hydrophila/efeitos dos fármacos , Chromobacterium/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Medicina Tradicional , Proteus mirabilis/efeitos dos fármacos , Proteus vulgaris/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Shigella sonnei/efeitos dos fármacos , Vibrio alginolyticus/efeitos dos fármacos , Vibrio cholerae/efeitos dos fármacos , Vibrio parahaemolyticus/efeitos dos fármacos , Vibrio vulnificus/efeitos dos fármacosRESUMO
AIM: Intestinal microsporidiosis are among the most frequent opportunistic diseases in immunocompromised subjects. This study aimed to evaluate the contribution of PCR for a better detection and species identification of microsporidia in stool specimens of HIV-infected patients. PATIENTS AND METHODS: Stool samples obtained from 119 HIV-infected Tunisian subjects were screened for intestinal microsporidiosis by light microscopy using Weber's modified Trichrome stain and by a PCR method using universal primers V1/PMP2 which amplified a common fragment of the small subunit rRNA gene of microsporidia. The obtained PCR products were then sequenced using an ABI PRISM 377 DNA sequencer. RESULTS: The results showed a better sensitivity of PCR in the detection of microsporidia with an infection rate of 14.3% significantly higher than that of 6.7% obtained by light microscopy (p=0.03). As previously described, intestinal microsporidiosis was associated with low CD4 cell counts; 23.9% infection rate in patients having CD4 cell count under 200/mm(3) against 5.6% in patients with higher CD4 cell count (p=0.008). The sequencing of 15 out of the 17 positive PCR products has confirmed in all cases the species identified based on the PCR fragment size i.e., 250pb for Enterocytozoon bieneusi (seven cases) and about 270pb for Encephalitozoon intestinalis (nine cases); one case revealed a double infection. CONCLUSION: PCR proved to be more effective than classical Trichrome stain for the diagnosis of intestinal microsporidiosis. Moreover, the ability of PCR to identify the species involved could also be useful for cases management.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Enteropatias/diagnóstico , Microsporidiose/diagnóstico , Reação em Cadeia da Polimerase/métodos , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/genética , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , DNA Fúngico/análise , DNA Fúngico/genética , Feminino , Infecções por HIV/complicações , Infecções por HIV/genética , Infecções por HIV/microbiologia , Humanos , Lactente , Recém-Nascido , Enteropatias/genética , Enteropatias/microbiologia , Masculino , Microsporidiose/complicações , Microsporidiose/genética , Microsporidiose/microbiologia , Microsporum/genética , Microsporum/isolamento & purificação , Pessoa de Meia-Idade , Adulto JovemRESUMO
Background: Uncontrolled hypertension (HTN) is a challenge for public health professionals all over the world. It is the leading and most important modifiable risk factor for coronary artery disease, congestive heart failure, stroke, renal diseases, and retinopathy. The aim of the present study was to estimate the prevalence of uncontrolled HTN among Palestinian hypertensive patients on treatment. In addition, the study aimed to explore the relationship between socio-demographic and clinical factors with HTN control as well as establish a comprehensive literature review for similar studies. Methods: A cross-sectional study was conducted. 218 hypertensive patients who met the inclusion criteria were included in the study. Results: HTN is not adequately controlled in over 60% of treated patients. Factors that were linked to uncontrolled HTN and were statistically significant as per this study were diabetes (p=0.010), high BMI (p=0.009), smoking (p < 0.0001), lower educational level (p=0.002), and monotherapy (p=0.004). Conclusion: The results suggest that effective efforts on improving HTN control are strongly needed. The efforts need to target hypertensive patients who are also smokers, diabetics, having a low education level, and have a higher-than-normal BMI.