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M Sabri

Publications and source records attributed to M Sabri.

18 recordsLinked to original sources
PubMed2006

CYP121, CYP51 and associated redox systems in Mycobacterium tuberculosis: towards deconvoluting enzymology of P450 systems in a human pathogen.

An extraordinary array of P450 (cytochrome P450) enzymes are encoded on the genome of the human pathogen Mycobacterium tuberculosis (Mtb) and in related mycobacteria and actinobacteria. These include the first characterized sterol 14alpha-demethylase P450 (CYP51), a known target for azole and triazole drugs in yeasts and fungi. To date, only two Mtb P450s have been characterized in detail: CYP51 and CYP121. The CYP121 P450 shows structural relationships with P450 enzymes involved in synthesis of polyketide antibiotics. Both P450s exhibit tight binding to a range of azole drugs (e.g. clotrimazole and fluconazole) and the same drugs also have potent effects on growth of mycobacteria (but not of e.g. Escherichia coli). Atomic structures are available for both Mtb CYP51 and CYP121, revealing modes of azole binding and intriguing mechanistic and structural aspects. This paper reviews our current knowledge of these and the other P450 systems in Mtb including recent data relating to the reversible conversion of the CYP51 enzyme between P450 (thiolate-co-ordinated) and P420 (thiol-co-ordinated) species on reduction of the haem iron in the absence of a P450 substrate. The accessory flavoprotein and iron-sulfur proteins required to drive P450 catalysis are also discussed, providing an overview of the current state of knowledge of Mtb P450 redox systems.

Azoles↗
PubMed2006

Attentional modulation in the detection of irrelevant deviance: a simultaneous ERP/fMRI study.

Little is known about the neural mechanisms that control attentional modulation of deviance detection in the auditory modality. In this study, we manipulated the difficulty of a primary task to test the relation between task difficulty and the detection of infrequent, task-irrelevant deviant (D) tones (1,300 Hz) presented among repetitive standard (S) tones (1,000 Hz). Simultaneous functional magnetic resonance imaging (fMRI)/event-related potentials (ERPs) were recorded from 21 subjects performing a two-alternative forced-choice duration discrimination task (short and long tones of equal probability). The duration of the short tone was always 50 msec. The duration of the long tone was 100 msec in the easy task and 60 msec in the difficult task. As expected, response accuracy decreased and response time (RT) increased in the difficult compared with the easy task. Performance was also poorer for D than for S tones, indicating distraction by task-irrelevant frequency information on trials involving D tones. In the difficult task, an amplitude increase was observed in the difference waves for N1 and P3a, ERP components associated with increased attention to deviant sounds. The mismatch negativity (MMN) response, associated with passive deviant detection, was larger in the easy task, demonstrating the susceptibility of this component to attentional manipulations. The fMRI contrast D > S in the difficult task revealed activation on the right superior temporal gyrus (STG) and extending ventrally into the superior temporal sulcus, suggesting this region's involvement in involuntary attention shifting toward unattended, infrequent sounds. Conversely, passive deviance detection, as reflected by the MMN, was associated with more dorsal activation on the STG. These results are consistent with the view that the dorsal STG region is responsive to mismatches between the memory trace of the standard and the incoming deviant sound, whereas the ventral STG region is activated by involuntary shifts of attention to task-irrelevant auditory features.

Acoustic Stimulation↗
PubMed2005

Biodiversity of cytochrome P450 redox systems.

P450s (cytochrome P450 mono-oxygenases) are a superfamily of haem-containing mono-oxygenase enzymes that participate in a wide range of biochemical pathways in different organisms from all of the domains of life. To facilitate their activity, P450s require sequential delivery of two electrons passed from one or more redox partner enzymes. Although the P450 enzymes themselves show remarkable similarity in overall structure, it is increasingly apparent that there is enormous diversity in the redox partner systems that drive the P450 enzymes. This paper examines some of the recent advances in our understanding of the biodiversity of the P450 redox apparatus, with a particular emphasis on the redox systems in the pathogen Mycobacterium tuberculosis.

Bacterial Proteins↗
PubMed2003

[Canine leishmaniasis in the Rif mountains (Moroccan Mediterranean coast): a seroepidemiological survey].

A sero-epidemiological survey has been conducted in several localities of the province of Nador to investigate canine leishmaniasis in the North-Eastern slope of the Rif mountains (Mediterranean coast of Morocco). Serum samples collected from 257 dogs were analysed using indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA) to detect anti-Leishmania infantum antibodies. Forty eight (18.7%) of the screened dogs were IFAT positive and 54 (21.0%) were ELISA positive; the concordance of the two methods was 96.1%. The prevalence of infection is significantly higher in dogs more than four years of age whereas no significant difference in prevalence of infection was seen between males and females. The frequent symptoms observed in seropositive dogs were the enlargement of lymph nodes (57.4%), emaciation (51.9%) and skin involvement (25.9%). However, 38.9% of those dogs showed no one of the major symptoms of visceral leishmaniasis. Leishmania isolated from three of the examined dogs was identified as L. infantum MON-1. These results show that the North-Eastern slope of the Rif mountains is one of the most active Mediterranean areas of visceral leishmaniasis and confirm that the dog is the main reservoir of L. infantum.

Age Distribution↗
PubMed2001

Effects of sequential and temporal probability of deviant occurrence on mismatch negativity.

The mismatch negativity (MMN) increases in amplitude as the probability of deviant occurrence decreases. It is unclear whether the determining variable is sequential probability (i.e. the probability of a deviant within a number of standards) or temporal probability (i.e. the probability of a deviant within a period of time). Eight subjects heard a train of frequently occurring 1000 Hz standard tones. The probability of a 1100 Hz pitch deviant was manipulated. In one condition the stimulus-onset-asynchrony (SOA) was 150 ms, with temporal probability of deviant occurrence being either 1/9.00, 1/4.50, 1/2.25, or 1/1.125 s (sequential probability being 1/60, 1/30, 1/15, or 1(deviant)/7.5(standards), respectively). In another condition the SOA was 600 ms, with temporal probability being either 1/9.00, 1/4.50, or 1/2.25 s (sequential probability being 1/15, 1/7.5, or 1/3.75, respectively). In a final condition, the SOA was 2400 ms with temporal probability being 1/9.00 s (sequential probability 1/3.75). Both sequential and temporal probabilities had a marked effect on the MMN. When a deviant occurred every 2.25, 4.50, or 9.00 s, the MMN increased as temporal probability decreased. When a deviant occurred once every 7.5 or 15 standards, the MMN was larger for lower sequential probability, but the effect was not significant. Nevertheless, when temporal probability was held constant at 1/9.00 s, the MMN increased as sequential probability decreased. At rapid rates of stimulus presentation, the MMN was largest. However, it was attenuated when the probability of deviant occurrence was very high perhaps due to the refractoriness of its generator. At the slowest rate, the MMN was diminished perhaps due to memory decay for the standard stimuli.

Acoustic Stimulation↗
PubMed2001

A confluence of contexts: asymmetric versus global failures of selective attention to stroop dimensions.

In 6 experiments probing selective attention through Stroop classification, 4 factors of context were manipulated: (a) psychophysical context, the distinctiveness of values along the color and word dimensions; (b) set size context, the number of stimulus values tested; (c) production context, the mode used to respond; and (d) covariate context, the correlation between the dimensions. The psychophysical and production contexts mainly caused an asymmetry in selective attention failure between colors and words, whereas the set size and covariate contexts contributed primarily to the average or global magnitudes of attentional disruption across dimensions. The results suggest that (a) Stroop dimensions are perceptually separable, (b) J.R. Stroop's (1935) classic findings arose from his particular combination of contexts, and (c) stimulus uncertainty and dimensional imbalance are the primary sources of task and congruity effects in the Stroop paradigm.

Adult↗
PubMed2000

Mismatch negativity to inclusions and omissions of stimulus features.

Two experiments were run to determine the effects of addition or removal of a stimulus feature on mismatch negativity (MMN). In the first experiment, a deviant stimulus was constructed by adding a click to a white noise standard stimulus. In the second experiment, the deviant was constructed by subtracting the click from the standard. In different conditions, the intensity of the click was varied. When the deviant was constructed by the addition of a click, a significant MMN was evident in those conditions in which click-to-noise ratio exceeded 1.0. When the deviant was constructed by the subtraction of the click, a significant negativity was found only when the click-to-noise ratio was very large. However, this negativity was accompanied by only a small polarity inversion at the mastoid. The MMN is thus best elicited when the deviant stimulus contains a new afferent element not present in the standard stimulus.

Acoustic Stimulation↗
PubMed2000

The mismatch negativity to frequency deviants during the transition from wakefulness to sleep.

This study examines the changes in the Mismatch Negativity during the transition from a waking, conscious state to one of sleep and unconsciousness. Auditory event-related potentials were recorded from eight participants during the sleep onset period. A 1,000 Hz-standard stimulus was presented every 600 ms. At random, on 20% of the trials, the standard was changed to either a large 2,000-Hz or a small 1,100-Hz deviant. During wakefulness, the large deviant elicited a larger, long-lasting MMN than the small deviant. Following the large deviant during relaxed wakefulness and Stage 2 sleep, the MMN continued to be elicited although it was reduced in amplitude. No significant MMN was recorded for either deviant in Stages 1 and slow wave sleep. The loss of consciousness therefore appears to have a marked effect on the MMN.

Adult↗
PubMed1993

Muslims with non-insulin dependent diabetes fasting during Ramadan: treatment with glibenclamide.

OBJECTIVE: To compare the efficacy of two glibenclamide regimens in patients with non-insulin dependent diabetes who were fasting during Ramadan and regular glibenclamide treatment in the non-fasting group. DESIGN: Non-randomised control group of patients who did not fast during Ramadan and two groups of patients who fasted randomised equally to one of two regimens: to take their usual morning dose of glibenclamide in the evening and their usual evening dose before dawn; or to follow this pattern but to reduce the total dose by a quarter. SETTING: Two university hospitals, one private hospital, and two private clinics in Casablanca and Rabat, Morocco. SUBJECTS: 591 diabetic patients (198 men, 391 women, two unspecified) with similar duration of diabetes and length and amount of glibenclamide treatment, of whom 542 completed the study. MAIN OUTCOME MEASURES: Serum fructosamine and total glycated haemoglobin concentrations and number of hypoglycaemic events. RESULTS: At the end of Ramadan there were no significant differences between the groups in fructosamine concentration (400 mumol/l in controls and 381 mumol/l and 376 mumol/l in the fasting groups); percentage of glycated haemoglobin (14.7%, 14.0%, and 13.6%); or number of hypoglycaemic events during Ramadan (11, 14, and 10). CONCLUSION: Glibenclamide is effective and safe for patients with non-insulin dependent diabetes who fast during Ramadan. The easiest regimen is to take the normal morning dose (together with any midday dose) at sunset and any evening dose before dawn.

Diabetes Mellitus, Type 2↗
PubMed1991

3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin.

3-Nitropropionic acid (3-NPA)--a suicide inhibitor of succinate dehydrogenase--is a widely distributed plant and fungal neurotoxin known to induce a damage to basal ganglia, hippocampus, spinal tracts and peripheral nerves in animals. Recent reports from Northern China indicate that 3-NPA is also likely to be responsible for the development of putaminal necrosis with delayed dystonia in children after ingestion of mildewed sugar cane. This article discusses the role of 3-NPA in the causation of the disease in China, its neurotoxic effects in animals and the potential role for this compound as a probe of selective neuronal vulnerability.

Animal Diseases↗
PubMed1979

Undesirable effects of hemometakinesia induced by vascular reconstruction.

Hemometakinesia, the borrowing of blood by one part of the body for use by other parts or tissues, is a well regulated physiologic mechanism involving selective vasodilation and vasoconstriction. It has been shown, however, that diversion of blood flow following vascular reconstruction may impoverish tissues from which the blood flow is borrowed, causing ischemia in these vascular beds. Observations on 12 patients out of a group of 100 who had undergone vascular reconstruction of a limb deterioration. It is suggested that the type and site of the vascular disorder and the expected diminution of blood flow in other involved arterial circuits should be considered in selecting the most appropriate vascular surgical procedure. Searching for and recognizing the hemodynamic significance of a silent lesion in the carotid or gastrointestinal circuit or in a contralateral limb may avert a vascular crisis after the primary lesion has been successfully treated.

Aged↗