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1.
Micromachines (Basel) ; 13(2)2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35208437

ABSTRACT

The converters used to integrate the ground power station of planes with the utility grid are generally created with silicon-insulated gate bipolar transistor (Si-IGBT)-based semiconductor technologies. The Si-IGBT switch-based converters are inefficient, oversized, and have trouble achieving pure sine wave voltages requirements. The efficiency of the aircraft ground power units (AGPU) can be increased by replacing existing Si-IGBT transistors with silicon carbide (SiC) IGBTs because of the physical constraints of Si-IGBT switches. The primary purpose of this research was to prove that the efficiency increase could be obtained in the case of using SiC-IGBTs in conventional AGPU systems with the realized experimental studies. In this study, three different experimental systems were discussed for this purpose. The first system was the traditional APGU system. The other two systems were single-phase test (SPT) and three-phase inverter systems, respectively. The SPT system and three-phase inverter systems were designed and implemented to compare and make analyses of Si-IGBTs and SiC-IGBTs performance. The efficiency and detailed hard switching behavior comparison were performed between the 1200-V SiC-IGBT- and 1200-V Si-IGBT-based experimental systems. The APGU system and Si-IGBT modules were examined, the switching characteristic and efficiency of the system were obtained in the first experimental study. The second experimental study was carried out on the SPT system. The single-pulse test system was created using Si-IGBTs and SiC-IGBTs switches in the second experimental system. The third experiment included a three-phase-inverter-based test system. The system was created with Si-IGBTs and SiC-IGBTs to compare the two different switch-based inverters under RL loads. The turning off and turning on processes of the IGBT switches were examined and the results were presented. The Si-IGBT efficiency was 77% experimentally in the SPT experimental system. The efficiency of the third experimental system was increased up to 95% by replacing the old Si transistor with a SiC. The efficiency of the three-phase Si-IGBT-based system was 86% for the six-switch case. The efficiencies of the SiC-IGBT-based system were increased to around 92% in the three-phase inverter system experimentally. The findings of the experimental results demonstrated that the SiC-IGBT had a faster switching speed and a smaller loss than the classical Si-IGBT. As a result of the experimental studies, the efficiency increase that could be obtained in the case of using SiC-IGBTs in conventional AGPU systems was revealed.

2.
J Hosp Infect ; 110: 165-171, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33561503

ABSTRACT

BACKGROUND: We investigated the clinical characteristics and risk factors for the isolation of multi-drug-resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients. METHODS: We retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls). RESULTS: Seventy-eight cases were identified (4.5 per 1000 intensive care unit (ICU) days, 95% confidence interval (CI) 3.6-5.7). Of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agents within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P=0.19). Mechanical ventilation days (adjusted odds ratio 1.062, 95% CI 1.012-1.114; P=0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (adjusted odds ratio 2.426, 95% CI 0.833-7.069; P= 0.104). CONCLUSION: In critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimizing the use of invasive devices, and to remove them as soon as their presence is no longer necessary.


Subject(s)
COVID-19/epidemiology , COVID-19/microbiology , COVID-19/physiopathology , Critical Illness , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacterial Infections/epidemiology , Adult , Female , Humans , Incidence , Male , Middle Aged , Prevalence , Qatar/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2
3.
Saudi J Biol Sci ; 27(1): 60-66, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31889818

ABSTRACT

Seedlings of alfalfa (Medicago sativa L.) were exposed to different concentrations of atmospheric ozone (20-30 (control), 40-60, 65-80, and 85-120 ppb) in four distinct areas in the Riyadh region, so as to decide how ozone affected some of the seedling cellular organelles. Results acquired utilizing transmission electron microscopy demonstrated certifiable impacts to exist on the cell organelles in the tissues of both the leaf mesophyll and stem cortex; contrasted with control plants, the chloroplasts seemed enlarged, irregular, different sizes, decomposed, and possibly dissolved, while the plastoglobules seemed deformed, more widely spaced, and enlarged, also the vacuoles contained no clear non-living components. Moreover, some parts of the cytoplasmic membranes were ruptured, with only a few vesicles created at all concentrations, particularly in plants exposed to concentrations of 65-80 and 85-120 ppb, while no effects were noted in these organelles in control plants or plants exposed to 40-60 ppb. High concentrations (85-120 ppb) led to enlarged, irregularly shaped nuclei and chromatin intensification; however, no clear effects of ozone were noted on the shapes of chloroplast starch grains or the mitochondria in leaf mesophyll and cortex cells in the stem. The high ozone concentrations can cause negative effects on the growth of alfalfa seedlings, leading to imbalances in their vital functions and acceleration of aging, thus potentially decreasing the total plant yield. The discoveries hence propose that alfalfa plants should not be planted near polluted areas, and that they can be utilized as bioindicators of air pollution by ozone.

4.
Eur J Pain ; 23(1): 135-141, 2019 01.
Article in English | MEDLINE | ID: mdl-30066465

ABSTRACT

BACKGROUND: Dexamethasone improves the quality and duration of peripheral nerve block when used as an adjuvant to local anaesthetic. We evaluated the effect of adding dexamethasone to bupivacaine on the duration of postoperative analgesia in patients undergoing knee arthroscopy using ultrasound-guided adductor canal block. METHODS: The study was a randomized, double-blinded trial. Sixty patients scheduled for arthroscopic anterior cruciate ligament reconstruction were randomly allocated into two groups to receive adductor canal block. The control group received 20 mL bupivacaine 0.5% + 2 mL normal saline, and the dexamethasone group received 20 mL bupivacaine 0.5% + 2 mL dexamethasone (8 mg). Measurements included onset and duration of sensory blockade, visual analog score, time to first analgesic requirement, analgesic consumption, satisfaction score and assessment of quadriceps strength. RESULTS: Duration of sensory block was significantly longer in the dexamethasone group (17.42 ± 5.24 h) than the control group (12.52 ± 1.16 h), p < 0.001. The visual analog score was significantly lower (p < 0.05) in the dexamethasone group. Time to first analgesic requirement was significantly longer in the dexamethasone group (13.37 ± 3.68 h) compared with the control group (10.57 ± 0.93 h), p < 0.001. Ketorolac dose as a rescue analgesic was significantly higher in the control group (p < 0.001), whereas patients' satisfaction score was significantly higher in the dexamethasone group (p < 0.001). CONCLUSION: The addition of dexamethasone to bupivacaine in adductor canal block provides prolonged postoperative analgesia and less postoperative analgesic consumption than bupivacaine alone in anterior cruciate ligament arthroscopic surgery. SIGNIFICANCE: Adding dexamethasone to bupivacaine in adductor canal block significantly increases the duration of sensory block, time to first analgesic requirement and patients' satisfaction score in anterior cruciate ligament arthroscopic surgery.


Subject(s)
Anesthetics, Local/therapeutic use , Anterior Cruciate Ligament Reconstruction/methods , Anti-Inflammatory Agents/therapeutic use , Arthroscopy/methods , Bupivacaine/therapeutic use , Dexamethasone/therapeutic use , Nerve Block/methods , Pain, Postoperative/prevention & control , Adult , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Ketorolac/therapeutic use , Male , Middle Aged , Muscle Strength , Pain, Postoperative/drug therapy , Patient Satisfaction , Quadriceps Muscle , Time Factors , Ultrasonography , Young Adult
5.
Saudi J Biol Sci ; 25(3): 441-445, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29686508

ABSTRACT

Black cutworm (BCW) Agrotis ipsilon, an economically important lepidopteran insect, has attracted a great attention. Bacillus thuringiensis (Bt) is spore forming soil bacteria and is an excellent environment-friendly approach for the control of phytophagous and disease-transmitting insects. In fact, bio-pesticide formulations and insect resistant transgenic plants based on the bacterium Bt delta-endotoxin have attracted worldwide attention as a safer alternative to harmful chemical pesticides. The major objective of the current study was to understand the mechanism of interaction of Bt toxin with its receptor molecule(s). The investigation involved the isolation, identification, and characterization of a putative receptor - vip3Aa. In addition, the kinetics of vip toxin binding to its receptor molecule was also studied. The present data suggest that Vip3Aa toxin bound specifically with high affinity to a 48-kDa protein present at the brush border membrane vesicles (BBMV) prepared from the midgut epithelial cells of BCW larvae.

6.
Eur J Clin Microbiol Infect Dis ; 33(5): 845-51, 2014 May.
Article in English | MEDLINE | ID: mdl-24292099

ABSTRACT

Iron acquisition is a virulence factor for Staphylococcus aureus. We assessed the efficacy of the iron chelator, deferasirox (Def), alone or in combination with vancomycin (Van) against two methicillin-resistant S. aureus (MRSA) strains in vitro and in a murine bacteremia model. In vitro time-kill assays were carried out against MRSA or vancomycin-intermediate S. aureus (VISA) strains. The impact of Def on Van binding to the surface of S. aureus was measured by flow cytometry. Furthermore, we compared the efficacy of Def, Van, or both drugs in treating S. aureus bacteremia in a murine model. Combination therapy reduced MRSA and VISA viability in vitro versus either drug alone or untreated controls (p < 0.005); this outcome was correlated with enhanced Van surface binding to S. aureus cells. In vivo, Def + Van combination therapy significantly reduced the bacterial burden in mice kidneys (p = 0.005) and spleen (p < 0.001), and reduced the severity of infection with MRSA or VISA strains compared to placebo-treated mice. Our results show that Def enhances the in vitro and in vivo capacity of Van-mediated MRSA killing via a mechanism that appears to involve increased binding of Van to the staphylococcal surface. Iron chelation is a promising, novel adjunctive therapeutic strategy for MRSA and VISA infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Benzoates/therapeutic use , Chelating Agents/therapeutic use , Staphylococcal Infections/drug therapy , Triazoles/therapeutic use , Vancomycin/therapeutic use , Animals , Bacterial Load , Deferasirox , Disease Models, Animal , Drug Therapy, Combination/methods , Iron/metabolism , Kidney/microbiology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/metabolism , Mice, Inbred BALB C , Microbial Sensitivity Tests , Microbial Viability/drug effects , Severity of Illness Index , Spleen/microbiology , Treatment Outcome
7.
East Mediterr Health J ; 17(7): 611-8, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21972486

ABSTRACT

There have been no systematic studies of diseases causing pleural effusion in Qatar. This prospective, hospital-based study involved all adult patients (> 15 years) with pleural effusions who were admitted to referral hospitals over a 1-year period. A total of 200 cases of pleural effusion were identified (152 males and 48 females); mean age 45.1 (SD 18.5) years. A majority of patients (73.5%) were non-Qataris, mostly from the Asian subcontinent. The most frequent cause of pleural effusions was tuberculosis (32.5%), followed by pneumonia (19%), cancer (15.5%) and cardiac failure (13%). The most frequent cause of malignant effusion was bronchogenic carcinoma (38.7%), whereas Gram-positive organisms were the most frequent isolates from empyema fluid (62.5%). Histological examination and culture of pleural biopsy were the most useful diagnostic workup for tuberculosis effusions, whereas repeated cytological examination of pleural fluid and pleural biopsy were most useful for malignant effusions.


Subject(s)
Pleural Effusion/etiology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pleural Effusion/epidemiology , Prospective Studies , Qatar/epidemiology
8.
(East. Mediterr. health j).
in English | WHO IRIS | ID: who-118668

ABSTRACT

There have been no systematic studies of diseases causing pleural effusion in Qatar. This prospective, hospital-based study involved all adult patients [> 15 years] with pleural effusions who were admitted to referral hospitals over a 1-year period. A total of 200 cases of pleural effusion were identified [152 males and 48 females]; mean age 45.1 [SD 18.5] years. A majority of patients [73.5%] were non-Qataris, mostly from the Asian subcontinent. The most frequent cause of pleural effusions was tuberculosis [32.5%], followed by pneumonia [19%], cancer [15.5%] and cardiac failure [13%]. The most frequent cause of malignant effusion was bronchogenic carcinoma [38.7%], whereas Gram-positive organisms were the most frequent isolates from empyema fluid [62.5%]. Histological examination and culture of pleural biopsy were the most useful diagnostic workup for tuberculosis effusions, whereas repeated cytological examination of pleural fluid and pleural biopsy were most useful for malignant effusions


Subject(s)
Prospective Studies , Pleural Effusion, Malignant , Empyema, Pleural , Empyema, Tuberculous , Pleural Effusion
9.
Mol Vis ; 16: 1487-95, 2010 Aug 04.
Article in English | MEDLINE | ID: mdl-20806080

ABSTRACT

PURPOSE: We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process. METHODS: Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, Müller cell activation, GS tyrosine nitration, and GS activity were determined. RESULTS: Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with Müller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats. CONCLUSIONS: These results suggest that diabetes-induced tyrosine nitration impairs GS activity and that CBD preserves GS activity and retinal neurons by blocking tyrosine nitration.


Subject(s)
Cannabidiol/pharmacology , Diabetes Mellitus, Experimental/enzymology , Diabetes Mellitus, Experimental/pathology , Glutamate-Ammonia Ligase/metabolism , Neuroprotective Agents/pharmacology , Retinal Neurons/enzymology , Retinal Neurons/pathology , Animals , Caspase 3/metabolism , Cell Death/drug effects , Cytoprotection/drug effects , Enzyme Activation/drug effects , Male , Neuroglia/drug effects , Neuroglia/enzymology , Neuroglia/pathology , Nitrosation/drug effects , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley
11.
J Neuroradiol ; 30(3): 172-9, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12843873

ABSTRACT

PURPOSE: Effective collateral blood flow seem to be an important factor associated with a small infarct volume and a good clinical outcome. We aimed to assess leptomeningeal collateral blood flow on source perfusion-weighted images in patients with acute stroke. MATERIALS AND METHODS: 29 patients with proximal middle cerebral artery occlusion (MCA alone, n=17; MCA + internal carotid artery [ICA] occlusion, n=12) were evaluated with MRI at baseline before thrombolytic therapy, and at day 60. Clinical evaluation was performed at days 0 and 60 with the National Institutes of Health Stroke Scale (NIHSS) score, and at day 60 with the modified Rankin score. We assessed (on source images of the dynamic contrast-enhanced T2*-weighted perfusion [PWI] sequence) the presence of a hypointensity consistent with delayed contrast arrival within the global perfusion deficit (delayed perfusion sign). We analyzed the extent of the area demonstrating such delayed perfusion (DP area) on source images of the PWI sequence, and compared it with the global perfusion (GP) abnormality shown by time-to-peak maps. We calculated the Spearman rank correlation coefficient between the DP/GP ratio and: 1. age; 2. clinical scores; 3. site of occlusion [MCA alone versus ICA+MCA occlusion]; 4. DWI lesion size at day 0, and T2WI lesion size at day 60; 5. PWI-derived parameters (time-to-peak [TTP], relative cerebral blood volume [rCBV], relative cerebral blood flow [rCBF], and peak height). All tests were bilateral and a p value<0.05 was considered as significant. RESULTS: Delayed perfusion areas of various size were found within the global perfusion deficit in all patients. High DP/GP ratio values were significantly correlated with: 1. better clinical scores at day 0 and day 60 (all p<=0.04); 2. smaller lesions at day 0 DWI and at day 60 T2WI (all p<=0.004); 3. ICA patency (r=0.49, p=0.01); 4. lower TTP delays, and higher values of rCBV, rCBF, and peak height. CONCLUSION: These preliminary data suggest that a delayed contrast filling observed on native perfusion-weighted images may be a marker of leptomeningeal collateral blood flow, and may lead to better clinical and morphological outcomes in acute ischemic stroke.


Subject(s)
Carotid Artery Diseases/pathology , Carotid Artery Diseases/physiopathology , Cerebrovascular Circulation/physiology , Collateral Circulation/physiology , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/physiopathology , Magnetic Resonance Imaging , Meninges/blood supply , Meninges/pathology , Stroke/pathology , Stroke/physiopathology , Acute Disease , Adult , Aged , Aged, 80 and over , Carotid Artery Diseases/complications , Female , Humans , Infarction, Middle Cerebral Artery/complications , Male , Meninges/physiopathology , Middle Aged , Stroke/etiology , Time Factors
12.
Int J Clin Pract ; 57(4): 354-5, 2003 May.
Article in English | MEDLINE | ID: mdl-12800475

ABSTRACT

A 60-year-old male was admitted with massive upper gastrointestinal bleeding following a gastric biopsy. Repeat gastroduodenoscopy failed to identify the source. Angiography identified bleeding from an arteriovenous malformation at the fundus of the stomach. This was controlled by embolisation.


Subject(s)
Arteriovenous Malformations/complications , Embolization, Therapeutic/methods , Gastrointestinal Hemorrhage/etiology , Angiography/methods , Arteriovenous Malformations/diagnostic imaging , Arteriovenous Malformations/therapy , Biopsy/adverse effects , Endoscopy, Gastrointestinal , Gastric Fundus/blood supply , Gastric Fundus/pathology , Gastrointestinal Hemorrhage/therapy , Hematemesis/etiology , Humans , Male , Melena/etiology , Middle Aged
13.
Phytochemistry ; 58(4): 599-602, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11576606

ABSTRACT

The biflavanone (2S,2"S)-7,7"-di-O-methyltetrahydroamentoflavone and five known flavonoids, 7-O-methylnaringenin, 7,3'-O-dimethylquercetin, 7-O-methylapigenin, 7-O-methylluteolin, and eriodictyol were isolated from the leaves of Rhus retinorrhoea Steud, Ex Olive. The biflavanone exhibited moderate antimalarial activity with IC50 0.98 microg/ml against Plasmodium falciparum (W2 Clone) and weak activity against P. falciparum (D6 Clone) with IC50 2.8 microg/ml. Nevertheless, it did not display any cytotoxicity. 7-O-Methylnaringenin showed weak antimicrobial activity against Candida albicans, C. krusei, Staphylococcus aureus, Mycobacterium smegmatis, M. intracellulare, and M. xenopi with MIC approximately 100 microg/ml. Characterization of each compound was based on spectral analysis and comparison with reported data.


Subject(s)
Anti-Infective Agents/isolation & purification , Antimalarials/isolation & purification , Biflavonoids , Flavonoids/isolation & purification , Rhus/chemistry , Animals , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antimalarials/chemistry , Antimalarials/pharmacology , Candida/drug effects , Flavonoids/chemistry , Flavonoids/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium/drug effects , Plasmodium falciparum/drug effects , Spectrum Analysis , Staphylococcus aureus/drug effects
14.
Epidemiology ; 12(1): 131-3, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11138809

ABSTRACT

This project signals an advance in cancer registration in the Middle East region. While it is too early to declare a major breakthrough, significant strides have been made toward establishing a basis for reliable information on the cancer burden at a population level and future collaborative efforts in cancer epidemiologic research and prevention.


Subject(s)
Neoplasms/epidemiology , Registries/statistics & numerical data , Humans , Middle East/epidemiology
15.
Infect Immun ; 68(10): 5953-9, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10992507

ABSTRACT

The ability of Candida albicans to respond to diverse environments is critical for its success as a pathogen. The RIM101 pathway controls gene expression and the yeast-to-hyphal transition in C. albicans in response to changes in environmental pH in vitro. In this study, we found that the RIM101 pathway is necessary in vivo for pathogenesis. First, we show that rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants have a significant reduction in virulence using the mouse model of hematogenously disseminated systemic candidiasis. Second, these mutants show a marked reduction in kidney pathology. Third, the rim101(-)/rim101(-) and rim8(-)/rim8(-) mutants show defects in the ability to damage endothelial cells in situ. Finally, we show that an activated allele of RIM101, RIM101-405, is a suppressor of the rim8(-) mutation in vivo as it rescues the virulence, histological, and endothelial damage defects of the rim8(-)/rim8(-) mutant. These results demonstrate that the RIM101 pathway is required for C. albicans virulence in vivo and that the function of Rim8p in pathogenesis is to activate Rim101p.


Subject(s)
Candida albicans/pathogenicity , Candidiasis/microbiology , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Animals , Candida albicans/genetics , Candida albicans/growth & development , Candidiasis/pathology , Candidiasis/physiopathology , Endothelium/cytology , Endothelium/pathology , Hydrogen-Ion Concentration , Kidney/microbiology , Kidney/pathology , Mice , Mice, Inbred BALB C , Virulence/genetics
16.
Infect Immun ; 67(7): 3193-8, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10377090

ABSTRACT

The disruption of a specific gene in Candida albicans is commonly used to determine the function of the gene product. We disrupted AAF1, a gene of C. albicans that causes Saccharomyces cerevisiae to flocculate and adhere to endothelial cells. We then characterized multiple heterozygous and homozygous mutants. These null mutants adhered to endothelial cells to the same extent as did the parent organism. However, mutants with presumably the same genotype revealed significant heterogeneity in their growth rates in vitro. This heterogeneity was not the result of the transformation procedure per se, nor was it caused by differences in the expression or function of URA3, a marker used in the process of gene disruption. The growth rate among the different heterozygous and homozygous null mutants was positively correlated with in vivo virulence in mice. It is possible that the variable phenotypes of C. albicans were due to mutations outside of the AAF1 coding region that were introduced during the gene disruption process. These results indicate that careful phenotypic characterization of mutants of C. albicans generated through targeted gene disruption should be performed to exclude the introduction of unexpected mutations that may influence pathogenicity in mice.


Subject(s)
Candida albicans/genetics , Fungal Proteins/genetics , Genes, Fungal , Mutation , Alleles , Animals , Candida albicans/growth & development , Candida albicans/pathogenicity , Endothelium, Vascular/microbiology , Gene Expression Regulation, Fungal , Heterozygote , Homozygote , Mice , Saccharomyces cerevisiae/genetics , Virulence/genetics
17.
Diabet Med ; 15(12): 1045-51, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9868980

ABSTRACT

We performed a cross-sectional, population-based survey of persons 20 years of age and older living in Cairo and surrounding rural villages. The purpose was to describe glycaemic control and the prevalence of microvascular and neuropathic complications among Egyptians with diagnosed diabetes, previously undiagnosed diabetes, impaired glucose tolerance, and normal glucose tolerance. A total of 6052 households were surveyed. The response rate was 76% for the household survey and 72% for the medical examination. Among people with previously diagnosed diabetes, mean haemoglobin A1c, was 9.0%. Forty-two per cent had retinopathy, 21% albuminuria, and 22% neuropathy. Legal blindness was prevalent (5%) but clinical nephropathy (7%) and foot ulcers (1%) were uncommon in persons with diagnosed diabetes. Among people with diagnosed diabetes, microvascular and neuropathic complications were associated with hyperglycaemia. Retinopathy was also associated with duration of diabetes; albuminuria with hypertension and hypercholesterolaemia; and neuropathy with age, female sex, and hypercholesterolaemia. Albuminuria was as common in people with previously undiagnosed diabetes (22%) as those with diagnosed disease (21%). Mean haemoglobin A1c was lower (7.8%) and retinopathy (16%) and neuropathy (14%) were less prevalent in people with previously undiagnosed disease. Ocular conditions, blindness, and neuropathy were prevalent in the non-diabetic population. The microvascular and neuropathic complications of diabetes are a major clinical and public health problem in Egypt.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/blood , Diabetic Angiopathies/epidemiology , Diabetic Neuropathies/epidemiology , Diabetic Retinopathy/epidemiology , Adult , Albuminuria , Confidence Intervals , Cross-Sectional Studies , Diabetes Mellitus/physiopathology , Diabetic Angiopathies/blood , Diabetic Neuropathies/blood , Diabetic Retinopathy/blood , Female , Glycated Hemoglobin/analysis , Health Surveys , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/epidemiology , Male , Middle Aged , Rural Population , Urban Population
18.
Antimicrob Agents Chemother ; 42(10): 2645-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9756770

ABSTRACT

The mechanisms of fluconazole resistance in three clinical isolates of Candida krusei were investigated. Analysis of sterols of organisms grown in the absence and presence of fluconazole demonstrated that the predominant sterol of C. krusei is ergosterol and that fluconazole inhibits 14alpha-demethylase in this organism. The 14alpha-demethylase activity in cell extracts of C. krusei was 16- to 46-fold more resistant to inhibition by fluconazole than was 14alpha-demethylase activity in cell extracts of two fluconazole-susceptible strains of Candida albicans. Comparing the carbon monoxide difference spectra of microsomes from C. krusei with those of microsomes from C. albicans indicated that the total cytochrome P-450 content of C. krusei is similar to that of C. albicans. The Soret absorption maximum in these spectra was located at 448 nm for C. krusei and at 450 nm for C. albicans. Finally, the fluconazole accumulation of two of the C. krusei isolates was similar to if not greater than that of C. albicans. Thus, there are significant qualitative differences between the 14alpha-demethylase of C. albicans and C. krusei. In addition, fluconazole resistance in these strains of C. krusei appears to be mediated predominantly by a reduced susceptibility of 14alpha-demethylase to inhibition by this drug.


Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Fluconazole/pharmacology , Candida/metabolism , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/metabolism , Drug Resistance, Microbial , Ergosterol/analysis , Fluconazole/metabolism , Oxidoreductases/antagonists & inhibitors , Sterol 14-Demethylase
19.
J Biol Chem ; 273(40): 26078-86, 1998 Oct 02.
Article in English | MEDLINE | ID: mdl-9748287

ABSTRACT

The Candida albicans PLB1 gene was cloned using a polymerase chain reaction-based approach relying on degenerate oligonucleotide primers designed according to the amino acid sequences of two peptide fragments obtained from a purified candidal enzyme displaying phospholipase activity (Mirbod, F., Banno, Y., Ghannoum, M. A., Ibrahim, A. S., Nakashima, S., Yasuo, K., Cole, G. T., and Nozawa, Y. (1995) Biochim. Biophys. Acta 1257, 181-188). Sequence analysis of a 6.7-kilobase pair EcoRI-ClaI genomic clone revealed a single open reading frame of 1818 base pairs that predicts for a pre-protein of 605 residues. Comparison of the putative candidal phospholipase with those of other proteins in data base revealed significant homology to known fungal phospholipase Bs from Saccharomyces cerevisiae (45%), Penicillium notatum (42%), Torulaspora delbrueckii (48%), and Schizosaccharomyces pombe (38%). Thus, we have cloned the gene encoding a C. albicans phospholipase B homolog. This gene, designated caPLB1, was mapped to chromosome 6. Disruption experiments revealed that the caplb1 null mutant is viable and displays no obvious phenotype. However, the virulence of strains deleted for caPLB1, as assessed in a murine model for hematogenously disseminated candidiasis, was significantly attenuated compared with the isogenic wild-type parental strain. Although deletion of caPLB1 did not produce any detectable effects on candidal adherence to human endothelial or epithelial cells, the ability of the caplb1 null mutant to penetrate host cells was dramatically reduced. Thus, phospholipase B may well contribute to the pathogenicity of C. albicans by abetting the fungus in damaging and traversing host cell membranes, processes which likely increase the rapidity of disseminated infection.


Subject(s)
Candida albicans/pathogenicity , Fungal Proteins/chemistry , Lysophospholipase/genetics , Saccharomyces cerevisiae Proteins , Virulence/genetics , Amino Acid Sequence , Animals , Base Sequence , Candidiasis/microbiology , Cell Adhesion/genetics , Chromosome Mapping , Cloning, Molecular , Disease Models, Animal , Gene Targeting/methods , Kidney/microbiology , Kidney/ultrastructure , Membrane Proteins , Mice , Mice, Inbred BALB C , Microscopy, Immunoelectron , Molecular Sequence Data , Sequence Alignment , Sequence Analysis, DNA
20.
Infect Immun ; 66(6): 3003-5, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9596782

ABSTRACT

The endothelial cell interactions of homozygous null mutants of Candida albicans that were deficient in secreted aspartyl proteinase 1 (Sap1), Sap2, or Sap3 were investigated. Only Sap2 was found to contribute to the ability of C. albicans to damage endothelial cells and stimulate them to express E-selectin. None of the Saps studied appears to play a role in C. albicans adherence to endothelial cells.


Subject(s)
Aspartic Acid Endopeptidases/metabolism , Candida albicans/pathogenicity , Endothelium, Vascular/microbiology , Fungal Proteins/metabolism , Candida albicans/enzymology , Cell Adhesion , E-Selectin/biosynthesis , Endothelium, Vascular/pathology , Humans
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