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1.
Artículo en Inglés | MEDLINE | ID: mdl-39259187

RESUMEN

BACKGROUND: Bridging from temporary microaxial left ventricular assist device (tLVAD) to durable left ventricular assist device (dLVAD) is playing an increasing role in the treatment of terminally ill heart failure patients. Scant data exits about the best implantation strategy. The aim of this study is to analyze differences in dLVAD implantation technique and effects on patient outcomes. METHODS: Data from 341 patients (19 European centers), between 01/2017 and 10/2022, who underwent bridge to bridge implantation from tLVAD to dLVAD were retrospectively analyzed. The outcomes of the different implantation techniques on cardiopulmonary bypass (CPB), extracorporeal life support (ECLS) or tLVAD were compared. RESULTS: Durable LVAD implantation was performed employing CPB in 70% of cases (n = 238, group 1), ECLS in 11% (n = 38, group 2) and tLVAD in 19% (n = 65, group 3).Baseline characteristics showed no significant differences in age (p = 0.140), BMI (p = 0.388), creatinine (p = 0.659), Meld score (p = 0.190) and rate of dialysis (p = 0.110). Group 3 had significantly less patients with preoperatively invasive ventilation and cardiopulmonary resuscitation before tLVAD implantation (p = 0.009 and p < 0.001 respectively). Concomitant procedures were performed more often in group 1 and 2 compared to group 3 (24%, 37% and 5%, respectively, p < 0.001).The 30-day mortality showed a significant better survival after inverse probability of treatment weighting in group 3, but the 1-year mortality showed no significant differences between groups (p = 0.012 and 0.581, respectively).Post-operative complications like rate of RVAD implantation or re-thoracotomy due to bleeding, post-operative respiratory failure and renal replacement therapy showed no significant differences between groups.Freedom from first adverse event like stroke, driveline infection or pump thrombosis during follow-up was not significantly different between groups.Post-operative blood transfusion within 24-hours were significantly higher in groups 1 and 2 compared to surgery on tLVAD support (p < 0.001 and p = 0.003, respectively). CONCLUSIONS: In our analysis, the transition from tLVAD to dLVAD without further circulatory support did not show a difference in post-operative long-term survival, but a better 30-day survival was reported. The implantation by using only tLVAD showed a reduction in post-operative transfusion rates, right heart failure and the re-thoracotomy rate without increasing the risk of postoperative stroke or pump thrombosis. In this small cohort study, our data supports the hypothesis that we could demonstrate dLVAD implantation on tLVAD is a safe and feasible technique in selected patients.

2.
World J Transplant ; 14(1): 87752, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38576753

RESUMEN

BACKGROUND: Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients. There are many indications for LT that vary between countries and settings. The outcome of LT depends on the available facilities and surgical expertise, as well as the types of liver graft donors available. AIM: To assess the clinical characteristics of patients from Bahrain who underwent LT overseas, and analyze factors affecting their survival. METHODS: In this retrospective cohort study, we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office, Ministry of Health, Kingdom of Bahrain, between 1997 and 2023. Demo graphic data, LT indication, donor-recipient relationship, overseas LT center, graft type, post-LT medications, and LT complications, were collected. Outcomes measured included the overall and 5-year LT survival rate. Fisher's exact, Pearson χ2, and Mann-Whitney U tests were used to compare the pediatric and the adults' group in terms of clinical characteristics, donor-recipient relationship, medication, complications, and outcome. Survival analysis was estimated via the Kaplan-Meier's method. Univariate and multivariate analyses were used to detect predictors of survival. RESULTS: Of the 208 eligible patients, 170 (81.7%) were sent overseas to undergo LT while 38 (18.3%) remained on the waiting list. Of the 170 patients, 167 (80.3%) underwent LT and were included in the study. The majority of the patients were Bahraini (91.0%), and most were males (57.5%). One-hundred-and-twenty (71.8%) were adults and 47 (28.3%) were children. The median age at transplant was 50.0 [interquartile range (IQR): 14.9-58.4] years. The main indication for pediatric LT was biliary atresia (31.9%), while that of adult LT was hepatitis C-related cirrhosis (35.0%). Six (3.6%) patients required re-transplantation. Most patients received a living-related liver graft (82%). Pediatric patients received more living and related grafts than adults (P = 0.038 and P = 0.041, respectively), while adult patients received more cadaveric and unrelated grafts. Most patients required long-term immunosuppressive therapy after LT (94.7%), of which tacrolimus was the most prescribed (84.0%), followed by prednisolone (50.7%), which was prescribed more frequently for pediatric patients (P = 0.001). Most patients developed complications (62.4%) with infectious episodes being the most common (38.9%), followed by biliary stricture (19.5%). Tonsilitis and sepsis (n = 12, 8.1% for each) were the most frequent infections. Pediatric patients experienced higher rates of infection, rejection, and early poor graft function than adult patients (P < 0.001, P = 0.003, and P = 0.025, respectively). The median follow-up time was 6.5 (IQR: 2.6-10.6) years. The overall survival rate was 84.4%, the 5-year survival rate, 86.2%, and the mortality rate, 15.6%. Younger patients had significantly better odds of survival (P = 0.019) and patients who survived had significantly longer follow-up periods (P < 0.001). CONCLUSION: Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries. Since LT facilities are not available, an overseas LT has offered them great hope.

3.
Heliyon ; 9(9): e20051, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809763

RESUMEN

Due to environmental concerns and budgetary constraints associated with synthetic fibers, natural fibers (NFr) are becoming increasingly popular as reinforcement in polymer composites (PCs) for structural components and construction materials. The surface treatment (ST) method is a well-established technique for enhancing the strength of interfacial bonding between NFr and the polymer matrix (PM). As a result, this research aims to determine the effect of ST with zinc oxide nanoparticles (ZnONPs) on the flexural properties of unsaturated polyester (UPE)/kenaf fiber (KF) nanocomposites. The hand lay-up technique was employed to produce KF-reinforced unsaturated polyester composites (KF/UPE) for this investigation. UPE/KF-ZnONPs composites were made with varying NFr loadings (weight percent), ranging from 10 to 40%. KF was treated with five distinct amounts of ZnONPs (from 1 to 5% weight percent). According to the findings of the investigation, the composite samples incorporating ZnONPs displayed superior optimum flexural properties compared to the untreated KF composite. It was found that 2% ZnONPs was optimal, and ST with ZnONPs could produce robust KF with improved flexural properties.

4.
Int J Soc Psychiatry ; 69(7): 1636-1640, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37092763

RESUMEN

BACKGROUND: Adverse childhood experiences is considered as major risk factor for several health problems and diseases during adulthood, such as hypertension, IHD, and eating disorders. The aim of current study was to measure the association between ACEs and malnutrition symptoms among sample of medical students in Fallujah University. METHODS: A convenience sample was used to recruit the participants; the data collection was carried out during December 2022. The questionnaire consisted from questions for demographical variables, questions for adverse childhood experiences and Short Nutritional Questionnaire was used for assessing the undernutrition symptoms among the subjects. RESULTS: Female subjects consisted 62.8% of the sample, 28.3% of the students had zero score of adverse childhood experience, 13% of the subjects had one score of ACEs and 45% of the participants had four or more of ACEs score. There was a statistically non- significant association between exposure to ACEs and undernutrition symptoms, p > .05. The logistic regression model revealed that female subjects had a risk of five folds for loss of appetite compare to male subjects (OR = 5.58, 95% CI [2.18, 14.31]). The females also had three folds for using nutritional supplement due to nutritional deficiencies compare to males (OR = 3.28, 95% CI [1.33, 8.1]). CONCLUSION: ACEs was not associated with undernutrition symptoms. Gender is significantly related with loss of appetite and using the nutritional supplement.


Asunto(s)
Experiencias Adversas de la Infancia , Desnutrición , Estudiantes de Medicina , Humanos , Masculino , Femenino , Adulto , Universidades , Irak/epidemiología , Desnutrición/epidemiología
5.
Int J Biomater ; 2023: 4219841, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36685114

RESUMEN

Bone plates are essential for bone fracture healing because they modify the biomechanical microenvironment at the fracture site to provide the necessary mechanical fixation for fracture fragments. The objective of this study was to determine cell availability, antibacterial activity, and wettability through a contact angle test. However, biocomposites that involve UHMWPE reinforced with n-HA and n-TiO2 particles at different fractions (0, 1.5, 2.5, 3.5, and 4.5%) and 5% from carbon and Kevlar fibers were fabricated by hot pressing technique. In vitro studies revealed good cell viability on the surface of the hybrid biocomposite even after 72 hr. The UHMEPE nanocomposite reinforced with carbon showed better cell attachment for fibroblasts than other UHMWPE nanocomposite materials reinforced with Kevlar fiber. The results of the contact angle measurements indicated that the incorporation of nanoparticles and the fiber reinforcement increased the wettability due to the hydrophilic character of nanobiocomposite, and also (UHMWPE-4.5% wt. TiO2-CF) biocomposite was the best wettability (∼48% as compared to neat UHMWPE). Antibacterial experiments involving Gram-positive bacteria, Staphylococcus aureus, confirm excellent bactericidal property for (UHMWPE-4.5% wt. TiO2-CF) biocomposite. Thermal analysis of the produced nanocomposites revealed that they had higher melting and crystallinity temperatures than pure UHMWPE.

6.
Cureus ; 15(12): e49958, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38179378

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease that can cause various health problems, including issues with the blood. One common blood-related symptom in SLE is immune thrombocytopenia (ITP), which leads to low platelet counts. In some cases, SLE patients with ITP may develop a rare but serious complication called subdural hematoma (SDH), which is a type of bleeding in the brain. This combination of conditions can be challenging to manage and has a high mortality rate. In a specific case, a 14-year-old girl with chronic ITP developed a sudden headache and was diagnosed with childhood-onset SLE, leading to the development of SDH. The treatment plan had to be adjusted, and a splenectomy was considered. It's important to be aware of the association between SLE, ITP, and SDH, especially in pediatric patients, and to conduct appropriate investigations in cases of severe headaches, to rule out life-threatening causes.

7.
Chemosphere ; 247: 125868, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31931320

RESUMEN

In the current study, a new hybrid ultrasonic-electrocoagulation reactor (U-E reactor) has been used to inactivate Escherichia coli in water. The new hybrid reactor consists of an ultrasonic bath fitted with four perforated aluminium electrodes. These perforated electrodes are designed to act as baffle-plates to enhance the water-mixing process. The electrodes eliminate the need for external mixing devices, which in turn, enhances the cost-effectiveness of the unit. Initially, the ability of the electrocoagulation to inactivate E. coli was optimised for different operating parameters such as electrolysing time (Te), electrodes spacing (ES) and current density (CD). The ultrasonic field was then applied over different time periods (Tu), during the course of the electrolysing process. Statistical analyses have been conducted to assess the relative effect of each operating parameter on the inactivation of E. coli. An economic study has also been conducted to assess the operating costs of the U-E reactor. The results revealed that the new U-E reactor inactivated 100% of the E. coli within 11 min of electrolysis at ES of 5 mm, CD of 1.5 mA/cm2, and an operation cost of 0.212 US $/m3. It was been established that the relative effect of operating parameters on E.coli inactivation followed the order: Te>Tu>CD>ES.


Asunto(s)
Electrocoagulación/métodos , Escherichia coli/crecimiento & desarrollo , Viabilidad Microbiana , Ondas Ultrasónicas , Purificación del Agua/métodos , Aluminio/química , Electrodos , Electrólisis , Concentración de Iones de Hidrógeno , Modelos Teóricos
8.
Addiction ; 112(8): 1470-1479, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28238214

RESUMEN

AIMS: To estimate the prevalence of tobacco, alcohol and drug use in Iraq using data from the Iraqi National Household Survey of Alcohol and Drug Use (INHSAD). DESIGN: A cross-sectional survey was conducted using a multi-stage cluster sampling method. Trained surveyors conducted face-to-face household interviews. SETTING: Iraq, from April 2014 to December 2014. PARTICIPANTS: A total of 3200 adult, non-institutionalized Iraqi citizens residing across all 18 governorates of Iraq. MEASUREMENTS: We estimated weighted prevalence and 95% confidence intervals (CIs) for life-time, past-year and past-month use of a variety of substances (tobacco, alcohol, prescription drugs and illicit drugs). For each substance, we also estimated whether individuals knew people who currently use the substance. FINDINGS: Self-reported past-month tobacco use was 23.2% (95% CI = 21.40, 25.19). Past-month alcohol use was 3.2% (95% CI = 2.58, 3.93). Women reported significantly lower prevalence for both tobacco and alcohol use compared with men (P-value < 0.01 for both). Only 1.4% (95% CI = 0.67, 3.02) reported past-month non-medical use of any prescription drugs. None of the women reported using any illicit drugs, and only 0.2% (95% CI = 0.07, 0.49) of men reported using any illicit drugs in the past month. Approximately 90.5% (95% CI = 88.58, 92.11) knew someone who uses tobacco, 42.4% (95% CI = 39.53, 45.24) knew someone who drinks alcohol, 27.9% (95% CI = 25.53, 30.45) knew someone who uses medication outside a doctor's instructions and 9.2% (95% CI = 7.87, 10.75) knew someone who uses an illicit drug. CONCLUSIONS: Psychoactive drug use is generally low in Iraq, tobacco being highest at an estimated 23.2%. Iraqi women report significantly less substance use than Iraqi men, which may be related to cultural gender norms. Discrepancy between self-report and 'knowing someone who uses a substance' suggests under-reporting in this population.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Encuestas Epidemiológicas/estadística & datos numéricos , Autoinforme , Trastornos Relacionados con Sustancias/epidemiología , Uso de Tabaco/epidemiología , Adolescente , Adulto , Análisis por Conglomerados , Estudios Transversales , Femenino , Humanos , Drogas Ilícitas , Entrevistas como Asunto , Irak/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por Sexo , Adulto Joven
9.
PLoS One ; 11(10): e0164916, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27798675

RESUMEN

In this paper, a new bandpass filter design has been presented using simple topology of stepped impedance square loop resonator. The proposed bandpass filter has been simulated and fabricated using a substrate with an insulation constant of 10.8, thickness of 1.27mm and loss tangent of 0.0023 at center frequency of 5.8 GHz. The simulation results have been evaluated using Sonnet simulator that is extensively adopted in microwave analysis and implementation. The output frequency results demonstrated that the proposed filter has high-quality frequency responses in addition to isolated second harmonic frequency. Besides, this filter has very small surface area and perceptible narrow band response features that represent the conditions of recent wireless communication systems. Various filter specifications have been compared with different magnitudes of perturbation element dimension. Furthermore, phase scattering response and current intensity distribution of the proposed filter have been discussed. The simulated and experimental results are well-matched. Lastly, the features of the proposed filter have been compared with other designed microstrip filters in the literature.


Asunto(s)
Impedancia Eléctrica , Fenómenos Electromagnéticos , Modelos Teóricos , Algoritmos , Simulación por Computador , Diseño de Equipo
10.
Asian Pac J Cancer Prev ; 17(S3): 175-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27165253

RESUMEN

Breast cancer is the most common cancer among the population as a whole and among females, yet it is highly curable if diagnosed at an early stage. Different methods are used to diagnose breast cancer. One of these methods features immunological tests using flow cytometry to determine T-lymphocyte (CD4/CD8) ratios in peripheral blood. One hundred patients with breast cancer (50 from Basra, Iraq, and 50 from Baku, Azerbaijan) confirmed to have breast cancer by histopathology were studied. Blood samples were collected from all patients before initiation of treatment and were used for analysis. The mean age of women from Basra was 51.2 ± 10.7 years and that of women from Baku was slightly higher at 54.8 ± 12.2 . The mean CD4/CD8 ratio in Basra was 1.4 and in Baku was 1.8 with P value < 0.05. The percentage of Basra patients who have CD4/CD8 value less than 1 was 50%, while the percentage for Baku patients was 24 % (p < 0.05). While the CD4/CD8 T-lymphocyte ratio might be useful for early diagnosis in patients with breast cancer parallel with other confirmed tests factors involved in explaining variation between countries such as that observed here need to be taken into account.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/diagnóstico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Subgrupos de Linfocitos T/inmunología , Azerbaiyán/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/inmunología , Relación CD4-CD8 , Femenino , Citometría de Flujo , Humanos , Irak/epidemiología , Pronóstico
11.
Biochim Biophys Acta ; 1858(9): 1999-2005, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27237728

RESUMEN

Daptomycin and A54145 are homologous lipopeptide antibiotics that permeabilize the cell membranes of Gram-positive bacteria. Membrane permeabilization depends on the presence of both phosphatidylglycerol (PG) and calcium, and it involves the formation of oligomeric transmembrane pores that consist of approximately 6-8 subunits. We here show that each lipopeptide molecule binds two calcium ions in separable, successive steps. The first calcium ion causes the lipopeptide molecule to bind to the target membrane, and likely to form a loosely associated oligomer. Higher calcium concentrations induce binding of a second ion, which produces the more tightly associated and more deeply membrane-inserted final, functional form of the oligomer. Both calcium-dependent steps are accompanied by fluorescence signals that indicate transition of specific amino acid residues into less polar environments, suggestive of insertion into the target membrane. Our findings agree with the earlier observation that two of the four acidic amino acid residues in the daptomycin molecule are essential for antibacterial activity.


Asunto(s)
Antibacterianos/química , Calcio/química , Daptomicina/química , Liposomas/química , Lipoproteínas/química
12.
Qatar Med J ; 2015(2): 14, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26835411

RESUMEN

BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. OBJECTIVES: This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. METHODS: The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. RESULTS: Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. CONCLUSION: SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease.

13.
PLoS One ; 9(12): e115412, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25536436

RESUMEN

This paper presents new Wide Bandpass Filter (WBPF) and Narrow Bandstop Filter (NBSF) incorporating two microstrip resonators, each resonator is based on 2nd iteration of Hilbert fractal geometry. The type of filter as pass or reject band has been adjusted by coupling gap parameter (d) between Hilbert resonators using a substrate with a dielectric constant of 10.8 and a thickness of 1.27 mm. Numerical simulation results as well as a parametric study of d parameter on filter type and frequency responses are presented and studied. WBPF has designed at resonant frequencies of 2 and 2.2 GHz with a bandwidth of 0.52 GHz, -28 dB return loss and -0.125 dB insertion loss while NBSF has designed for electrical specifications of 2.37 GHz center frequency, 20 MHz rejection bandwidth, -0.1873 dB return loss and 13.746 dB insertion loss. The proposed technique offers a new alternative to construct low-cost high-performance filter devices, suitable for a wide range of wireless communication systems.


Asunto(s)
Simulación por Computador , Electrónica/instrumentación , Filtración/instrumentación , Fractales , Conductividad Eléctrica , Diseño de Equipo , Modelos Teóricos
14.
Subst Use Misuse ; 49(13): 1759-63, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24827867

RESUMEN

BACKGROUND: Reports suggest increased use of alcohol, prescription drugs, and illicit drugs in Iraq in the past decade, which may portend an increase in substance use disorders (SUDs) and, thus, an increased need for treatments. OBJECTIVES/METHODS: To develop better information on the nature and extent of drug and alcohol use in Iraq, the Iraqi Ministry of Health, with support from the US government and technical assistance from US researchers, held an initial Iraqi Community Epidemiology Work Group meeting in May 2012 in Baghdad. Drug seizure data were the primary data source, provided by Iraqi law enforcement and customs officials. Ministry of Health officials presented data from hospitals (medical and psychiatric), outpatient clinics, and health centers, as well as from surveys of medical patients, pharmacy patients, and prisoners. RESULTS: The data suggest that the most commonly used substances are alcohol, hashish, and prescription drugs. New drugs in Iraq's drug use scene include the amphetamine-type substances "Captagon" and crystal methamphetamine, and the painkiller tramadol. Seizures of Captagon, methamphetamine, Afghan opium, teriac (a crude form of opium), and heroin at border crossings may indicate that these substances are becoming more popular. A plan for an ongoing program of CEWG meetings was developed. CONCLUSIONS: Drug and alcohol use in Iraq is increasing and new drugs are appearing in the country. An ongoing program for monitoring drug use trends and informing Iraqi policy makers is important for public health planning, including the development of strategies to identify citizens with SUDs and provide them treatment.


Asunto(s)
Consumo de Bebidas Alcohólicas/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Femenino , Humanos , Irak/epidemiología , Masculino , Vigilancia de la Población
15.
Biochim Biophys Acta ; 1838(10): 2425-30, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24857935

RESUMEN

Daptomycin is a lipopeptide antibiotic that is used clinically to treat severe infections caused by Gram-positive bacteria. Its bactericidal action involves the calcium-dependent binding to membranes containing phosphatidylglycerol, followed by the formation of membrane-associated oligomers. Bacterial cells exposed to daptomycin undergo membrane depolarization, suggesting the formation of channels or pores in the target membranes. We here used a liposome model to detect and characterize the permeability properties of the daptomycin pores. The pores are selective for cations, with permeabilities being highest for Na(+), K(+), and other alkali metal ions. The permeability is approximately twice lower for Mg(++), and lower again for the organic cations choline and hexamethonium. Anions are excluded, as is the zwitterion cysteine. These observations account for the observed depolarization of bacterial cells by daptomycin and suggest that under typical in vivo conditions depolarization is mainly due to sodium influx.


Asunto(s)
Daptomicina/química , Liposomas/química , Modelos Químicos , Bacterias/química , Bacterias/metabolismo , Cationes/química , Membrana Celular/química , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular , Potenciales de la Membrana , Metales/química
16.
J Biol Chem ; 289(17): 11584-11591, 2014 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-24616102

RESUMEN

Daptomycin is an acidic lipopeptide antibiotic that, in the presence of calcium, forms oligomeric pores on membranes containing phosphatidylglycerol. It is clinically used against various Gram-positive bacteria such as Staphylococcus aureus and Enterococcus species. Genetic studies have indicated that an increased content of cardiolipin in the bacterial membrane may contribute to bacterial resistance against the drug. Here, we used a liposome model to demonstrate that cardiolipin directly inhibits membrane permeabilization by daptomycin. When cardiolipin is added at molar fractions of 10 or 20% to membranes containing phosphatidylglycerol, daptomycin no longer forms pores or translocates to the inner membrane leaflet. Under the same conditions, daptomycin continues to form oligomers; however, these oligomers contain only close to four subunits, which is approximately half as many as observed on membranes without cardiolipin. The collective findings lead us to propose that a daptomycin pore consists of two aligned tetramers in opposite leaflets and that cardiolipin prevents the translocation of tetramers to the inner leaflet, thereby forestalling the formation of complete, octameric pores. Our findings suggest a possible mechanism by which cardiolipin may mediate resistance to daptomycin, and they provide new insights into the action mode of this important antibiotic.


Asunto(s)
Antibacterianos/farmacología , Transporte Biológico/efectos de los fármacos , Cardiolipinas/fisiología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Daptomicina/farmacología , Transporte Biológico/fisiología , Calorimetría , Bacterias Grampositivas/efectos de los fármacos
17.
Biochim Biophys Acta ; 1828(2): 302-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23084999

RESUMEN

Daptomycin is a clinically important lipopeptide antibiotic that kills Gram-positive bacteria through membrane depolarization. Its activity requires calcium and the presence of phosphatidylglycerol in the target membrane. Calcium and phosphatidylglycerol also promote the formation of daptomycin oligomers, which have been assumed but not proven to be required for the bactericidal effect. Daptomycin shares substantial structural similarity with another lipopeptide antibiotic, A54145; the two have identical amino acid residues in 5 out of 13 positions and similar ones in 4 more positions. We here examined whether these conserved residues are sufficient for oligomer formation. To this end, we used fluorescence energy transfer and excimer fluorescence to detect hybrid oligomers of daptomycin and CB-182,462, a semisynthetic derivative of A54145. Mixtures of the two compounds indeed produced hybrid oligomers, but at the same time displayed a significantly less than additive antibacterial activity against Bacillus subtilis. The existence of functionally impaired oligomers indicates that oligomer formation is indeed important for antibacterial function. However, it also shows that oligomerization is not sufficient; once formed, the oligomers must take another step in order to acquire antibacterial activity. Thus, the amino acid residues shared between daptomycin and CB-182,462 suffice for formation of the oligomer, but not for its subsequent activation.


Asunto(s)
Antibacterianos/farmacología , Compuestos de Bencilideno/farmacología , Daptomicina/química , Lipopéptidos/química , Morfinanos/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/metabolismo , Calorimetría/métodos , Membrana Celular/metabolismo , Dimiristoilfosfatidilcolina/química , Diseño de Fármacos , Lipoproteínas/farmacología , Liposomas/química , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Perileno/química , Fosfatidilgliceroles/química , Espectrometría de Fluorescencia/métodos
18.
Confl Health ; 6(1): 3, 2012 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-22839108

RESUMEN

An increased prevalence of birth defects was allegedly reported in Iraq in the post 1991 Gulf War period, which was largely attributed to exposure to depleted uranium used in the war. This has encouraged further research on this particular topic. This paper reviews the published literature and provided evidence concerning birth defects in Iraq to elucidate possible environmental exposure. In addition to published research, this review used some direct observation of birth defects data from Al-Ramadi Maternity and Paediatric Hospital in Al-Anbar Governorate in Iraq from1st July 2000 through 30th June 2002. In addition to depleted uranium other war-related environmental factors have been studied and linked directly or indirectly with the increasing prevalence of birth defects. However, the reviewed studies and the available research evidence do not provide a clear increase in birth defects and a clear indication of a possible environmental exposure including depleted uranium although the country has been facing several environmental challenges since 1980.

19.
Biochim Biophys Acta ; 1818(7): 1642-7, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22387459

RESUMEN

Daptomycin is a lipopeptide antibiotic that kills Gram-positive bacteria by depolarizing their cell membranes. This antibacterial action of daptomycin is correlated with the formation of membrane-associated oligomers. We here examine the number of subunits contained in one oligomer using fluorescence resonance energy transfer (FRET). The results suggest that the oligomer contains approximately 6 to 7 subunits, or possibly twice this number if it spans both membrane monolayers.


Asunto(s)
Membrana Celular/química , Daptomicina/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Multimerización de Proteína , Antibacterianos/química , Antibacterianos/farmacología , Membrana Celular/efectos de los fármacos , Daptomicina/farmacología , Bacterias Grampositivas/efectos de los fármacos , Cinética , Quinurenina/química , Lipopéptidos/química , Lipopéptidos/farmacología , Modelos Químicos , Modelos Moleculares , Subunidades de Proteína/química , Subunidades de Proteína/farmacología
20.
Biochim Biophys Acta ; 1818(3): 673-8, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22079564

RESUMEN

Daptomycin is a lipopeptide antibiotic that binds to and depolarizes bacterial cell membranes. Its antibacterial activity requires calcium and correlates with the content of phosphatidylglycerol in the target membrane. Daptomycin has been shown to form oligomers on liposome membranes. We here use perylene excimer fluorescence to further characterize the membrane-associated oligomer. To this end, the N-terminal fatty acyl chain was replaced with perylene-butanoic acid. The perylene derivative retains one third of the antibacterial activity of native daptomycin. On liposomes containing phosphatidylcholine and phosphatidylglycerol, as well as on Bacillus subtilis cells, the perylene-labeled daptomycin forms excimers, which shows that the N-terminal acyl chains of neighboring oligomer subunits are in immediate contact with one another. In a lipid bicelle system, oligomer formation can be titrated with stoichiometric amounts of phosphatidylglycerol. Therefore, the interaction of daptomycin with a single molecule of phosphatidylglycerol is sufficient to trigger daptomycin oligomerization.


Asunto(s)
Calcio/química , Daptomicina/química , Perileno/química , Fosfatidilgliceroles/química , Antibacterianos/química , Antibacterianos/farmacología , Bacillus subtilis/crecimiento & desarrollo , Calcio/farmacología , Daptomicina/farmacología , Estructura Molecular , Perileno/farmacología , Fosfatidilgliceroles/farmacología
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