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Glass samples with varying compositions was prepared by standard approach. The composition of the samples was (50-x) B2O3--25TeO2--25BaO-xDy2O3, with x ranging from 0 to 1.25 mol%. XRD profiles confirmed that the samples were amorphous, as there were no long-range lattice arrangements observed. The successful preparation of amorphous samples was further confirmed by the absence of sharp lines & peaks. The optical properties of the obtained samples were analyzed. That a decrease in Eopt values resulted in a higher value of the refractive index (n) for the glasses. However, when the concentration of Dy2O3 exceeded certain levels (0.75, 1, and 1.25 mol%), the refractive index (n) decreased due to an increase in Eopt values. Experimental measurements using a NaI(Tl) detector were conducted to determine the radiation shielding parameters (LAC and MAC), as well as the (HVL), (TVL), & (MFP) of the glasses against gamma rays emitted by 137Cs and 60Co isotopes at energies of 0.662, 1.173, and 1.333 MeV. Excellent agreement was observed when comparing the experimental results with theoretical calculations using Phy-x/PSD software program. This suggests that the fabricated glasses have great potential for various applications in the field of optics and can effectively shield against radiation. [ABSTRACT FROM AUTHOR]

In this study, a series of barium-boro-tellurite glass hosts with varying concentration of Dy2O3 doping (0 to 1.25 mol%) were made by melt-quenching method. A study was conducted to investigate how Dy2O3 dopants affect the physical and spectroscopic traits of glasses. Raw materials including barium oxide (BaO), tellurium dioxide (TeO2), boron oxide (B2O3), and dysprosium oxide (Dy2O3) were used to produce these glasses. XRD patterns of the samples showed a broad hump and absence of long-range periodic lattice arrangements, indicating their amorphous nature. The Raman spectral analyses displayed the various vibration modes where the most intense band caused by BaO vibrations at 300 cm-1 and 450 cm-1 corresponding to the symmetric stretching vibration mode of Te–O–Te intra-chain bridges. The peak at 750 cm-1 was due to TeO4 and Te-O-Te vibration modes. The value of optical band gap energy was decreased from 3.155 to 2.1894 eV and then increase at higher Dy2O3 level (0.75 to 1.25 mol%). At Dy3+ contents between 0.25 to 1.25 mol% seven absorption bands were observed at 390, 424, 452, 750, 797, 895 and 1092 nm due to the electronic transitions in Dy3+. The glass refractive indices were raised from 2.3563 to 2.6584 and then decreased at higher Dy2O3 contents which was mainly because of the generation of more bridging oxygen (BO) in the glass matrix. The value of glass electronic polarizability and oxide ions polarizability calculated using LorentzLorenz equation showed a decrease with the rise of Dy2O3 contents, which was ascribed to the presence of fewer non-bridging oxygen (NBO). The optical basicity of the proposed glass hosts was calculated using Duffy and Ingram equation which was decreased with the increase of doping contents. In addition, the optical transmission was increased and reflection loss was reduced with increasing Dy+3 levels. The value of metallization parameter below 1 proved the true amorphous nature of the prepared samples. All the glasses revealed blue and yellow photoluminescence emission peaks due to 4F9/2→ 6H15/2, and 4F9/2 →6H13/2 transitions in Dy3+, respectively. The proposed glass compositions may be beneficial for the advancement of solid-state lasers. [ABSTRACT FROM AUTHOR]

Background: Trends of paediatric emergency visits (ED) for dental conditions have been broadly discussed; however, little has been published in the Canadian context., Aim: To describe the utilization of ED for dental conditions among children and to investigate demographic characteristics influencing its use., Design: A comprehensive review of records of all children aged 1-17 years who attended the ED service of a paediatric hospital in Montreal, Canada, for dental conditions over a 10-year period (2004-2013) was completed. Information on the child's principal dental diagnosis, sociodemographic data, and source of referral was obtained., Results: A total of 10 905 paediatric ED visits were seen during the study period. Among the children, 54.7% were male and the majority was younger than 6 years old. Dental caries constituted the most common reason for ED presentation comprising close to 43% of total visits for a dental complaint. Females, teenagers, and self-referred children were more likely to experience ED visits due to non-traumatic dental conditions., Conclusions: The utilization of ED for dental conditions has increased among pre-school children in the last decade and was mostly due to caries-related dental problems. Effective preventive strategies are needed to improve the oral health condition of children., (© 2020 BSPD, IAPD and John Wiley & Sons Ltd.)

Introduction: The aim of this multicentric prospective study was to evaluate the clinical and radiographic outcomes of Biodentine (BD) pulpotomies on permanent teeth with complicated crown fractures., Methods: This study was carried out in 2 hospital-based dental departments in Quebec, Canada. Children seeking emergency care after trauma to anterior permanent teeth were invited to participate in this study. The treatment outcome was assessed clinically and radiographically at 1 week and 1, 3, 6, 12, 18, and 24 months after treatment., Results: Forty-five patients between the ages of 8 and 16 years (mean, 10.8 ± 2.4) were included in this study. Fifty-one teeth were treated with a BD pulpotomy. The study showed a survival rate of 100% and a success rate of 91%. Four failures were noted at 1-, 6-, and 15-month follow-up, and the teeth were subsequently treated with either conventional root canal therapy or regenerative endodontic procedure. Dental sensitivity to cold reported by patients reduced over time, and more teeth responded normally to pulp vitality tests during the course of this study. Slight discoloration was noted on 8 teeth (17%). Radiographic outcomes showed dentinal bridge formation in 91% of cases, and all immature teeth showed continued root formation., Conclusions: BD is a suitable material for pulpotomies on anterior permanent teeth with complicated crown fractures. It may be a good alternative to mineral trioxide aggregate pulpotomies because it does not cause significant discoloration, and it allows root maturation., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Cannabis products (marijuana, weed, hashish) are among the most widely abused psychoactive drugs in the world, due to their euphorigenic and anxiolytic properties. Recently, hair analysis is of great interest in analytical, clinical, and forensic sciences due to its non-invasiveness, negligible risk of infection and tampering, facile storage, and a wider window of detection. Hair analysis is now widely accepted as evidence in courts around the world. Hair analysis is very feasible to complement saliva, blood tests, and urinalysis. In this review, we have focused on state of the art in hair analysis of cannabis with particular attention to hair sample preparation for cannabis analysis involving pulverization, extraction and screening techniques followed by confirmatory tests (e.g., GC-MS and LC-MS/MS). We have reviewed the literature for the past 10 years' period with special emphasis on cannabis quantification using mass spectrometry. The pros and cons of all the published methods have also been discussed along with the prospective future of cannabis analysis., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

This study aimed to assess the oral health status of refugee children in comparison with that of Canadian children. In addition, we investigated the extent to which demographic factors are associated with caries experience in this population. Children with a confirmed refugee status and Canadian children (control group) matched for age and sex composed the study population. A comprehensive review of dental charts was completed to assess children's demographic data, caries experience, oral hygiene and gingival health status. The majority of refugee children had never seen a dentist before their arrival to Canada. Refugee children had significant higher dmft/DMFT scores than Canadian children (7.29 ± 5.1 and 4.47 ± 5, respectively; p < 0.0001). Furthermore, individual factors, such as refugee status (OR = 5.08; 95% CI = 2.31-11.1) and child age (OR = 2.17; 95% CI = 1.04-4.51) were significantly associated with caries experience. Access to appropriate dental care to refugee children should be a key priority for health care providers and policy makers.

Pachyonychia congenita (PC) is a rare autosomal dominant condition caused by heterozygous mutation in one of five keratin genes. The purpose of this paper is to report a five-day-old infant with PC whose initial presentation revealed multiple malformed natal teeth and gingival lesions on the alveolar crest. Further investiga- tions led to genetic molecular testing of the child and his parents, which revealed a de novo and novel missense variant of KRT17 (c. 307C>T, p. Arg103Cys), resulting in a non-conservative amino-acid substitution and a diagnosis of PC. This case high- lights the need for multidisciplinary care and the relevance of molecular investigations for patients with multiple natal teeth. (J Dent Child 2019;86(1):61-3)
Received September 26, 2018; Last Revision November 19, 2018; Accepted November 19, 2018.

Objectives: The present study aimed at determining the antioxidant activity, total phenols and flavonoids and to evaluate the antiproliferative activity of ethanolic extract of Matricaria recutita L. (chamomile). The antioxidant activities were measured using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The total phenolic content was measured by the Folin-Ciocalteu assay. The flavonoid content was determined using the aluminum chloride method. The MTT assay was used to estimate the antiproliferative activities against human hepatoma (HepG2) cancer cell line. We assessed the mode of action of the extract as a cancer preventive agent and reported its ability to regulate tumor angiogenesis by down regulating in a dose dependent manner the expression of some proteins involved in the process., Results: The percentage inhibition of DPPH scavenging activity was dose-dependent ranging between (94.8% ± 0.03) at 1.50 mg/mL and (84.2% ± 0.86) at 0.15 mg/mL. It showed high polyphenols (21.4 ± 0.327 mg GAE/g) and high flavonoids content (157.9 ± 2.22 mg QE/g). Effect of extract was investigated against HepG2 cells. A dose-dependent reduction in cell viability was recorded in cells treated with the extract. The IC 50 was ~ 300 µg/mL. It significantly inhibited the level of important prerequisite angiogenesis markers both in HepG2 cells and ex vivo.

Background: Here, we determined in vitro antioxidant activity, total phenols and flavonoids and evaluated antiproliferative activity of three medicinal plant extracts: Trigonella foenum-graecum (Fenugreek), Cassia acutifolia (Senna) and Rhazya stricta (Harmal)., Methods: The leaves of the three medicinal plants were extracted with 70% ethanol. Antioxidant activities of the extracts were determined by using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Total flavonoid and phenolic contents were determined using colorimetric assays. MTT assay was used to estimate the antiproliferative activities of the extracts against human hepatoma (HepG2) cancer cell line. In addition, the effects of R. stricta extract on cell cycle, colony formation, and wound healing of HepG2 cells and tube formation of HUVEC cells were assessed., Results: Percentage inhibition of DPPH scavenging activity were dose-dependent and ranged between (89.9% ± 0.51) and (28.6% ± 2.07). Phenolic contents ranged between (11.5 ± 0.013) and (9.7 ± 0.008) mg GAE/g while flavonoid content ranged between (20.8 ± 0.40) and (0.12 ± 0.0.01) mg QE/g. Antiproliferative results of the extracts were found to be consistent with their antioxidant activity. Among the extracts evaluated, that of R. stricta showed the best antioxidant, antiproliferative and antimetastatic activities at low concentration. It also inhibited the colony-formation capacity of HepG2 cells and exhibited antiangiogenic activity. Cell cycle analysis showed significant arrest of cells at G2/M phase 12 and 48 h after treatment and significant arrest at G1/S phase after 24 h of treatment. Consistent data were observed in western blot analysis of protein levels of Cdc2 and its cyclin partners., Conclusions: These findings introduce R. stricta as a potentially useful anti-metastatic agent and a novel potential anti-tumour agent for hepatocellular carcinoma (HCC) treatment.

Research shows that immunoassay techniques are not the best choice for the estimation of vitamin D in human blood samples. The main reasons are that some immunoassays are not able to distinguish between 25-OHD3 and 25-OHD2 vitamin D metabolites. Furthermore, immunoassays cannot differentiate between 25OHD and inactive epimers of vitamin D. Vitamin D epimers and isobars have been known to overlap with the 25OHD signals and give false positives when tested. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) can differentiate between 25OHD3 and 25OHD2. Separating epimers and isobars (which have the same molecular weight) from vitamin D is achieved through chromatographic separation from actual 25OHD peaks, although this could also cause inaccuracies in vitamin D measurements. The main aim of this study was to develop and validate an improved LC-MS/MS method (using a Shimadzu 8060 system) that could accurately detect and quantitate up to 10 different metabolites of vitamin D, as well as differentiate the epimers and isobars. The secondary aim was to apply the developed LC-MS/MS method for the accurate measurement of blood vitamin D levels in the Emirati population. The Shimadzu 8060 system was run using positive ion electrospray ionization (ESI) in Dynamic Multiple Reaction Monitoring (DMRM) mode for quantification. The method involved blood sample collection from 80 Emirati volunteers, followed by serum extraction and liquid-liquid extraction. The chromatography column used for the analysis was an Ascentis Express F5. Precursor and product ions were detected using a Shimadzu 8060 LC-MS/MS system, and 10 metabolites of vitamin D were detected and quantified, including epimers and isobars. The method validation showed good sensitivity, recovery, linearity, precision, specificity, and accuracy. Furthermore, the data showed that vitamin D epimer 3-epi-25OHD and isobar 7-α-hydroxy-4-cholesten-3-one (7αC4) accounted for a significant portion of vitamin D results in the Emirati population. We report a more reliable, reproducible, and robust LC-MS/MS method for the accurate detection of 25OHD (vitamin D) in the Emirati population. The method has the capacity to detect and separate 10 metabolites of vitamin D as well as separate 25OHD from co-eluting epimers and isobars. The method has also been successfully implemented in gauging vitamin D deficiency in the Emirati population. Thus, this improved LC-MS/MS method could prove very useful in accurately estimating the levels of vitamin D in the Emirati population and in further clinical studies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: The purposes of this study were to determine the prevalence of malocclusion among children with autism spectrum disorder (ASD) and to describe the most common malocclusion traits in this population., Methods: This cross-sectional study included patients diagnosed with ASD aged between 5 and 18 years. Randomly selected healthy children with the same demographic characteristics comprised the control group. Dental charts were reviewed to obtain the children's sociodemographic characteristics and type of occlusion. Information on each child's molar occlusion classification (Angle classification), midline deviation, crossbite, open bite, overbite, overjet, and crowding were recorded. The statistical analysis used descriptive analysis, the Pearson chi-square test, and multivariate logistic regression., Results: Ninety-nine children comprised the ASD group, and 101 children were in the control group. Our results demonstrated a significantly higher prevalence of malocclusion in children with ASD compared with the control group (P <0.001). Patients with ASD were significantly more likely to have posterior crossbite (P = 0.03), increased overjet (P <0.0001), and severe maxillary crowding (P <0.01). Furthermore, children with ASD were more likely to have malocclusion than non-ASD children, independently of their demographic characteristics (odds ratio, 2.6; 95% confidence interval, 1.46, -4.65)., Conclusions: The prevalence of malocclusion was higher among children with ASD. Posterior crossbite, increased overjet, and severe maxillary crowding were the most common malocclusion traits in these children., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to determine the rate of self-correction and predictive factors for irreversible outcome of mesial ectopic eruption of permanent maxillary first molars (EE), in a sample population where no interceptive treatment was initiated., Methods: Charts of patients diagnosed with EE were reviewed, and radiographs were analyzed for predictive factors reported in the literature., Results: Sixty-five EE were included in the study; 46 (71 percent) self-corrected, of which one-third occurred after age nine years. Space loss, with an average of approximately three mm, occurred in 18 EE (28 percent). Increased magnitude of impaction, degree of resorption of the primary second molar, severe lock, and bilateral occurrence were positively correlated with irreversible EE. Multiple regression analysis was positive for increased magnitude of impaction when adjusted for gender and bilateral occurrence., Conclusion: Spontaneous self-correction occurred in 71 percent of permanent maxillary first molars with ectopic eruption; one third of self-corrections occurred after nine years of age. Delaying treatment of ectopic eruption of permanent maxillary first molars may be a viable option when the outcome is uncertain. Increased magnitude of impaction was the most reliable predictor associated with irreversible outcome.

Introduction: The treatment of immature necrotic permanent teeth presents several clinical challenges in endodontics. Regenerative endodontic procedures (REPs) permit root development, increased canal wall thickness, and apical closure. This longitudinal cohort study aimed to evaluate the long-term clinical and radiographic outcomes of REPs of immature necrotic permanent teeth over a 30-month period., Methods: This study was performed at the Division of Dentistry of the Montreal Children's Hospital, Montreal, Quebec, Canada. Twenty-eight immature necrotic permanent teeth from 22 patients were included in this study. All teeth were treated with a standardized REP protocol. Patients had follow-up appointments at 1, 2, 3, 6, 12, 18, 24, and 30 months. At each appointment, signs and symptoms were evaluated. Radiographic evaluation was also performed by a calibrated endodontist in order to analyze different parameters., Results: Our results show a high survival rate (96.4%), clinical success (92.8%), and resolution of apical pathology (100%). Significant increases in the average root length (8.1%, P < .0001) and root thickness area (11.6%, P = .03) were observed after 30 months. In the study period, a significant decrease in the apical diameter was also noted, with 30.8% of the cases showing complete apical closure. Teeth with more immature stages of root development had a higher percentage of change in root thickness, length, and apical diameter; however, these results were not statistically significant., Conclusions: Teeth treated with REPs presented resolution of symptoms. Although clinical meaningful change was not achieved in all cases, increased root thickness, root length, and apical closure were observed at 30 months., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The MraY transferase catalyzes the first membrane step of bacterial cell wall peptidoglycan biosynthesis, namely the transfer of the N-acetylmuramoyl-pentapeptide moiety of the cytoplasmic precursor UDP-MurNAc-pentapeptide to the membrane transporter undecaprenyl phosphate (C55P), yielding C55-PP-MurNAc-pentapeptide (lipid I). A paralogue of MraY, WecA, catalyzes the transfer of the phospho-GlcNAc moiety of UDP-N-acetylglucosamine onto the same lipid carrier, leading to the formation of C55-PP-GlcNAc that is essential for the synthesis of various bacterial cell envelope components. These two enzymes are members of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily, which are essential for bacterial envelope biogenesis. Despite the availability of detailed biochemical information on the MraY enzyme, and the recently published crystal structure of MraY of Aquifex aeolicus, the molecular basis for its catalysis remains poorly understood. This knowledge can contribute to the design of potential inhibitors. Here, we report a detailed catalytic study of the Bacillus subtilis MraY and Thermotoga maritima WecA transferases. Both forward and reverse exchange reactions required the presence of the second substrate, C55P and uridine monophosphate (UMP), respectively. Both enzymes did not display any pyrophosphatase activity on the nucleotide substrate. Moreover, we showed that the nucleotide substrate UDP-MurNAc-pentapeptide, as well as the nucleotide product UMP, can bind to MraY in the absence of lipid ligands. Therefore, our data are in favour of a single displacement mechanism. During this "one-step" mechanism, the oxyanion of the polyprenyl-phosphate attacks the β-phosphate of the nucleotide substrate, leading to the formation of lipid product and the liberation of UMP. The involvement of an invariant aspartyl residue in the deprotonation of the lipid substrate is discussed., (Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background: Sialorrhea is a common manifestation of several neurological disorders. The use of intraglandular onabotulinum toxin A (OBTXA) injection has been recognized to effectively treat sialorrhea. As OBTXA injection reduces salivary flow rate and alters salivary quality, its use may have a detrimental effect on oral health., Aim: To examine the effect of OBTXA injection on caries experience and salivary pH of neurologically impaired children with sialorrhea., Design: Twenty-five children receiving OBTXA treatment and 25 control children were enrolled in the study. Whole saliva was collected to determine salivary pH. All participants underwent an interview on their dietary habits. Dental clinical examinations were carried out to evaluate caries experience and oral hygiene level., Results: Overall, mean salivary pH value was significantly lower in the OBTXA group (6.92 ± 0.77) compared with the control group (7.36 ± 0.70). Caries activity was significantly higher in the OBTXA group (P = 0.01). The regression analyses showed a significant association between OBTXA treatment and salivary pH value (P = 0.03). Results from the logistic regression show that dental caries was significantly associated with OBTXA treatment (OR = 1.73, CI = 1.14-27.3)., Conclusions: The study showed an intricate relationship between OBTXA treatment and oral findings. Hence, special dental care should be given to children receiving OBTXA treatment., (© 2015 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions., Methods: Biopsies were obtained from the stomachs of two groups of patients (n = 40) undergoing fiber-optic endoscopy due to upper gastrointestinal symptoms. In the first group (n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption (cellular respiration), cellular adenosine triphosphate (ATP), glutathione (GSH), and caspase activity. In the second group of patients (n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level., Results: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate (mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min(-1) mg(-1), ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high and ATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration (O2. μmol/L min(-1) mg(-1)) was slightly higher in the corpus than the antrum (0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues (310 ± 135 vs 322 ± 155, P = 0.692)., Conclusion: The corpus mucosa was metabolically more active than the antrum tissue. The data in this study will help in understanding the pathophysiology of gastric mucosa.

We investigated the association between in-hospital and peri-hospital mortality and body mass index (BMI)/waist circumference (WC) in a prospective acute coronary syndrome (ACS) registry in the Arabian Gulf. No significant associations with in-hospital mortality were found. Normal BMI had highest peri-hospital mortality, notably those with high WC. In logistic regression of mortality on obesity measures and potential confounders, the effects of obesity measures were no longer significant. In-hospital death increased by 5% with age and decreased by 42% in males. Mortality increased 3.7-fold with ST-elevation myocardial infarction (STEMI) and 3.0-fold with heart failure (HF) but decreased by 33% with dyslipidemia. Peri-hospital death increased by 4% with age and decreased by 30% in males. Mortality increased 2.8-fold with STEMI and 2.4-fold with HF. In- and peri-hospital mortality in ACS is significantly associated with age, gender, STEMI, HF, and dyslipidemia but not obesity measures., (© The Author(s) 2013.)

In populations with high prevalences of iron deficiency and thalassemia trait, many apparently healthy individuals have abnormal erythroid parameters, which may cause diagnostic problems in clinical practice. We studied the prevalence and causes of red cell parameter values outside their reference ranges in 394 healthy individuals of Bedouin Arab origin, who had complete blood counts (CBCs), hemoglobin (Hb) analyses and serum ferritin tests done. Their mean age ± standard deviation (SD) was 24.8 ± 4.9 years and 51.8% were females. Overall, 53.0% (209/394) had low Hb, MCV or MCH or high RDW. Anemia was present in 27.0% (55/204) of the women and 3.0% (6/190) of the men. Overall prevalence of MCV < 80.0 fL was 45.0% (176/394) and MCH < 27.0 pg was 48.0% (190/394); RDW > 14.0% was found in 21.0% (43/204) of women and 7.0% (14/190) of men. Of the women, 16.0% had iron deficiency anemia (33/204) and 65.0% had ferritin values of < 30.0 μg/L (133/204). The estimated prevalence of α-thalassemia (α-thal) trait in men was 32.0% (60/190) and that of β-thalassemia (β-thal) trait in both sexes was 3.0% (12/394). In conclusion, half of the healthy Emirati population have abnormal CBC values. For clinical purposes, they require reference standards for red cells that are derived from their own population. Screening of women for iron deficiency is justified due to a high prevalence of iron deficiency.

Atorvastatin (a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor) is a widely used cholesterol-lowering drug, which is recognized for its potential hepatotoxicity. This study investigated in vitro effects of this agent on hepatic tissue respiration, ATP content, caspase activity, urea synthesis and histology. Liver fragments from Taylor Outbred and C57Bl/6 mice were incubated at 37°C in Krebs-Henseleit buffer continuously gassed with 95% O2: 5% CO2 in the presence and absence of atorvastatin. Phosphorescence O2 analyzer that measured dissolved [O2] as a function of time was used to monitor cellular mitochondrial O2 consumption. The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin was used to monitor caspase activity. The rates of hepatocyte respiration (μM O2 min(-1) mg(-1)) in untreated samples were 0.15±0.07 (n=31). The corresponding rates for samples treated with 50 nM (therapeutic concentration), 150 nM or 1.0 μM atorvastatin for ≤13 h were 0.13±0.05 (n=19), p=0.521. The contents of hepatocyte ATP (pmol(-1) mg(-1)) in untreated samples were 40.3±14.0 and in samples treated with 1.0 μM atorvastatin for ≤4.5 h were 48.7±23.9 (p=0.7754). The concentrations of urea (mg/dL mg(-1), produced over 50 min) for untreated samples were 0.061±0.020 (n=6) and for samples treated with 1.0 μM atorvastatin for ≤6 h were 0.072±0.022 (n=6), p=0.3866. Steadily, hepatocyte caspase activity and histology were unaffected by treatments with up to 1.0 μM atorvastatin for ≤6 h. Thus, the studied murine model showed preserved hepatocyte function and structure in the presence of high concentrations of atorvastatin.

Background: The aim of this study was to develop liver tissue preparation suitable for investigating toxins. Hepatocyte respiration, ATP content, urea synthesis, caspase activity and morphology were measured as a function of in vitro incubation time. Mice were anesthetized by sevoflurane inhalation. Small liver fragments were then rapidly excised and incubated at 37°C in Krebs-Henseleit buffer (continuously gassed with 95% O2: 5% CO2) for up to 6 h. Phosphorescence O2 analyzer was used to determine the rate of cellular mitochondrial O2 consumption (kc, μM O2 min-1 mg-1). Cellular ATP was measured using the luciferin/luciferase system. The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspase activity; cleaved AMC moieties (reflecting caspase activity) were separated on HPLC and detected by fluorescence., Findings: Respiration was inhibited by cyanide, confirming the oxidation occurred in the respiratory chain. The values of kc (mean ± SD) for 0≤ t ≤6 h were 0.15 ± 0.02 μM O2 min-1 mg-1 (n = 18, coefficient of variation, CV = 13%), ATP content 131 ± 69 pmol mg-1 (1≤ t ≤6 h, n = 16, CV = 53%), synthesized urea 0.134 ± 0.017 mg/dL mg-1 in 50 min (0≤ t ≤6 h, n = 14, CV = 13%), and AMC peak area 62,540 ± 26,227 arbitrary units mg-1 (1≤ t ≤6 h, n = 3, CV = 42%). Hepatocyte morphology and organelles were reasonably persevered., Conclusions: The described liver tissue preparation demonstrates stable hepatocyte structure, ultrastructure and biomarkers for up to 6 h, permitting in vitro studies.

The consumption of dates with coffee is common among Arabs and may affect postprandial hyperglycemia ex-cursion. The study aimed to determine the effect of coffee on the glycemic index of a common variety of dates (Khalas) tested in healthy and type 2 diabetes mellitus individuals. Study subjects were thirteen healthy volunteers (mean age: 40.2±6.7 years) and ten diabetic participants with a mean HbA1c of 6.6±(0.7%) and a mean age of 40.8±5.7 years. Each subject participated in five days of tests with 50 g of glucose and 50 g equivalent of available carbohydrates from the dates (with/without coffee). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min, and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. Glycemic indices were determined as ratios of the incremental areas under the response curves for the interventions. Statistical analyses were performed using the independent samples and paired t-tests. Mean±SE glycemic indices of the Khalas dates for the healthy individuals were 55.1±7.7 and 52.7±6.2 without and with coffee consumption, respectively. Similar values were observed for those with diabetes (53.0±6.0 and 41.5±5.4). Differences between glycemic indices of Khalas with or without coffee were not significant (p=0.124). There were no significant differences in glycemic index between the diabetic and healthy subjects (p=0.834 and p=0.202 without and with coffee respectively). In conclusion, at least in the short term, coffee does not adversely affect capillary glucose levels following Khalas dates consumption in healthy and diabetic volunteers.

Background: Gender-related differences in mortality of acute coronary syndrome (ACS) have been reported. The extent and causes of these differences in the Middle-East are poorly understood. We studied to what extent difference in outcome, specifically 1-year mortality are attributable to demographic, baseline clinical differences at presentation, and management differences between female and male patients., Methodology/principal Findings: Baseline characteristics, treatment patterns, and 1-year mortality of 7390 ACS patients in 65 hospitals in 6 Arabian Gulf countries were evaluated during 2008-2009, as part of the 2nd Gulf Registry of Acute Coronary Events (Gulf RACE-2). Women were older (61.3±11.8 vs. 55.6±12.4; P<0.001), more overweight (BMI: 28.1±6.6 vs. 26.7±5.1; P<0.001), and more likely to have a history of hypertension, hyperlipidemia or diabetes. Fewer women than men received angiotensin-converting enzyme inhibitors (ACE), aspirin, clopidogrel, beta blockers or statins at discharge. They also underwent fewer invasive procedures including angiography (27.0% vs. 34.0%; P<0.001), percutaneous coronary intervention (PCI) (10.5% vs. 15.6%; P<0.001) and reperfusion therapy (6.9% vs. 20.2%; P<0.001) than men. Women were at higher unadjusted risk for in-hospital death (6.8% vs. 4.0%, P<0.001) and heart failure (HF) (18% vs. 11.8%, P<0.001). Both 1-month and 1-year mortality rates were higher in women than men (11% vs. 7.4% and 17.3% vs. 11.4%, respectively, P<0.001). Both baseline and management differences contributed to a worse outcome in women. Together these variables explained almost all mortality disparities., Conclusions/significance: Differences between genders in mortality appeared to be largely explained by differences in prognostic variables and management patterns. However, the origin of the latter differences need further study.

Gender differences exist in many aspects of acute coronary syndrome (ACS), including presentation and delay in diagnosis and treatment. The aim of the study was to evaluate gender-related differences in ACS patients in the United Arab Emirates (UAE). We analyzed a subset (n = 1697) of the Gulf Registry of Acute Coronary Events (Gulf RACE) data collected in 2007 of patients with ACS from 18 UAE hospitals. Women were significantly older (mean age: 64.0 ± 12.4 years for females and 50.9 ± 10.6 years for males, P < .001), more often had cardiac risk factors and were significantly less treated with β-blockers and reperfusion therapy. The adjusted mortality rate of women was 4.6% versus 1.2% in men (P < .001). Heart failure was higher in females compared with men (24.6% vs 12.5%; P < .001). Reasons for the high in-hospital mortality in women need to be investigated further.

Screening for β -thalassemia trait (BTT) relies on measuring hemoglobin (Hb) A2. Since multiple factors can affect HbA2 levels, the screening can become unreliable. In 1356 healthy Arabs enrolled into a federally funded premarital BTT screening program, the effects of iron deficiency (ID), α (+)-thalassemia trait, gender, smoking, and tribalism on HbA2 were studied. The complete blood count and hemoglobin fractions were determined on the entire cohort; serum ferritin (<15  μ g/L) in 391 subjects was used to determine ID. BTT was present in 29 (2.1%) subjects (HbA2 > 3.5%). Among 77(20.3%) subjects with ID, the mean HbA2 (2.30 ± 0.23%) was 0.2% lower than in subjects without iron deficiency (2.50 ± 0.24%, P < 0.0001). In 65 (38%)/172 subjects with phenotypic α (+)-thalassemia trait, the mean HbA2 (2.43 ± 0.24%) was 0.13% lower than in subjects without α (+)-thalassemia trait, P < 0.0001. The mean HbA2 did not differ between males and females, smokers and nonsmokers, and between the tribes. Thus, 35 (2.6%) subjects with HbA2 between 3.2 and 3.5% were at a risk of false negative diagnosis of BTT. Since iron deficiency and α (+)-thalassemia are both common and both lower HbA2, modifications in screening recommendations for BTT are proposed.

Background: Heart failure (HF) is a serious complication of acute coronary syndromes (ACS), and is associated with high in-hospital mortality and poor long-term survival. The aims of this study were to describe the clinical characteristics, management and in-hospital outcomes of coronary syndrome (ACS) patients with HF in the United Arab Emirates., Findings: The study was selected from the Gulf Registry of Acute Coronary Events (Gulf RACE), a prospective multi-national, multicenter registry of patients hospitalized with ACS in six Middle East countries. The present analysis was focused on participants admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 and were analyzed in terms of HF (Killip class II/III and IV) on admission. Of 1691 patients (mean age: 52.6 ± 11.7 years; 210 Females, 1481 Males) with ACS, 356 (21%) had an admission diagnosis of HF (Killip class II/III and IV). HF patients were less frequently males (19.2% vs. 34.3%; P < 0.001). HF was more frequently associated with hypertension (64.3% vs. 43.9%; P < 0.001), hyperlipidemia (49.4% vs. 31.8%; P < 0.001) and diabetes mellitus (DM) (51.1% vs. 36.2%; P < 0.001). HF was significantly associated with in-hospital mortality (OR = 11.821; 95% CI: 5.385-25.948; P < 0.001). In multivariate logistic regression, age, hyperlipidemia, heart rate and DM were associated with higher in-hospital HF., Conclusions: HF is observed in about 1 in 5 patients with ACS in the UAE and is associated with a significant increase in in-hospital mortality and other adverse outcomes.

The purpose of this case series was to report on the use of a technique of revascularization for necrotic immature permanent teeth, several problems encountered, and solutions to those problems. Eighteen pulp revascularizations were performed in 2009 using the original protocol of revascularization (adapted from the AAE/AAPD joint meeting in 2007 in Chicago). The protocol consisted of opening the canal and disinfecting it with sodium hypochlorite, sealing in a triple antibiotic paste for 2-6 weeks, re-opening, re-irrigating, creating a blood clot in the canal, and sealing with an MTA barrier over the clot. Three problems were encountered during the treatment: (1) bluish discoloration of the crown; (2) failure to produce bleeding; and (3) collapse of the mineral trioxide aggregate (MTA) material into the canal. Modifications to solve these problems included: changing one of the antibiotics, using a local anesthesia without epinephrine, and adding collagen matrix to the blood clot.

Objective: To evaluate clinical profiles, management and in-hospital outcomes of acute coronary syndrome (ACS) patients with metabolic syndrome (MetS) in the United Arab Emirates (UAE)., Methods: MetS was defined according to the criteria for its diagnosis by the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI). Participants were admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the Gulf Registry of Acute Coronary Events (Gulf RACE) project. We compared baseline characteristics, treatment patterns, and in-hospital outcomes stratified by MetS status., Results: Of 1259 patients with ACS in the UAE (mean age: 52 ± 11 years, 88.8% males), the majority (n = 851, 67.6%) had MetS. MetS patients were more frequently males (86.4 vs 13.6%; P < 0.001). They were more obese (waist circumference and BMI, P < 0.001) as compared with non-MetS patients. MetS was more frequently associated with hypertension (51.1 vs 37.7%; P < 0.001) and diabetes mellitus (45.6 vs 24.3%; P < 0.001). After multivariate adjustment, certain MetS criteria rather than MetS itself were associated with higher in-hospital mortality and heart failure. Paradoxically, hypertension was associated with lower in-hospital mortality., Conclusions: Prevalence of MetS among patients with ACS in our study population was high. Certain MetS criteria were associated with higher in-hospital mortality and heart failure.

We describe the baseline characteristics, management, and in-hospital outcomes of patients in the United Arab Emirates (UAE) with DM admitted with an acute coronary syndrome (ACS) and assess the influence of DM on in-hospital mortality. Data was analyzed from 1697 patients admitted to various hospitals in the UAE with a diagnosis of ACS in 2007 as part of the 1st Gulf RACE (Registry of Acute Coronary Events). Of 1697 patients enrolled, 668 (39.4%) were diabetics. Compared to patients without DM, diabetic patients were more likely to have a past history of coronary artery disease (49.1% versus 30.1%, P < 0.001), hypertension (67.2% versus 36%, P < 0.001), and prior revascularization (21% versus 11.4%, P < 0.001). They experienced more in-hospital recurrent ischemia (8.5% versus 5.1%; P = 0.004) and heart failure (20% versus 10%; P < 0.001). The mortality rate was 2.7% for diabetics and 1.6% for nondiabetics (P = 0.105). After age adjustment, in-hospital mortality increased by 3.5% per year of age (P = 0.016). This mortality was significantly higher in females than in males (P = 0.04). ACS patients with DM have different clinical characteristics and appear to have poorer outcomes.

The systematic structure-activity relationship (SAR) of the muraymycins (MRYs) using an Ugi four-component reaction (U4CR) was investigated. The impact of the lipophilic substituent on antibacterial activity was significant, and the analogues 8 and 9 having a lipophilic side chain exhibited good activity against a range of Gram-positive bacterial pathogens, including MRSA and VRE. Further investigation of compounds 8 and 9 revealed these analogues to be selective inhibitors of the MraY transferase and nontoxic to HepG2 cells. The SAR of the accessory urea-peptide moiety indicated that it could be simplified. Our SAR study of the MRYs suggests a probable mechanism for inhibition of the MraY, where the inner moiety of the urea-dipeptide motif interacts with the carbohydrate recognition domain in the cytoplasmic loop 5. The predicted binding model would provide further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on MRYs.

Stable analogs of bacterial transferase MraY substrate or product with a pyrophosphate surrogate in their structure are described. β-ketophosphonates were designed as pyrophosphate bioisosteres and were investigated as UDP-GlcNAc mimics. The developed strategy allows introduction of structural diversity at a late stage of the synthesis. The biological activity of the synthesized compounds was evaluated on the MraY enzyme.

Background: This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus., Methods: Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance., Results: Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83)., Conclusion: The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet., Trial Registration Number: ClinicalTrials.gov NCT01307904.

New inhibitors of the bacterial tranferase MraY are described. A scaffold strategy based on the diazepanone central core of liposidomycins, natural inhibitors of MraY has been developed. It involves the introduction of key structural fragments required for biological activity on enantiopure diazepanones by reductive amination, esterification and glycosylation. Biological evaluation of these compounds on MraY enzyme revealed interesting inhibitory activity for compounds displaying three fragments on the scaffold: a palmitoyl chain, an aminoribose part and an alkyluracil moiety. The inhibitors were also evaluated on MurG enzyme. The best compounds resulted in inhibition with IC50 values in the 100 μM range for one or the other enzyme., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aims: To investigate the prevalence of undiagnosed type 2 diabetes (T2D) at primary health care (PHC) clinics, and to assess the quality of care of diabetic patients followed at a tertiary hospital diabetes center in Abu Dhabi, United Arab Emirates (UAE)., Methods: Between May 2009 and October 2010, adult patients attending two PHC clinics, and adult diabetic patients attending the diabetes center, were invited to participate in the study. After overnight fast, participants returned for interview and laboratory tests. Undiagnosed T2D was defined by FPG ≥ 7.0 mmol/l or HbA1c ≥ 6.5%. Quality of care was assessed by reported care practices and achievement of internationally recognized targets., Results: Out of 239 patients at PHC clinics without history of T2D, 14.6% had undiagnosed T2D, and 31% had increased risk of diabetes (FPG 5.6-7.0 mmol/l or HbA1c 5.7-6.5%). The independent predictors of undiagnosed T2D were age (adjusted OR per year 1.07, 95% CI 1.04-1.11, p < 0.001) and BMI ≥ 25 (adjusted OR 4.2, 95% CI 0.91-19.7, p = 0.033). Amongst all 275 diagnosed T2D patients, including those attending PHC clinics and those followed at the diabetes center, it was found that 40.1% followed dietary recommendations, 12% reported visiting a diabetes educator, 28.2% walked for exercise, and 13.5% attained recognized targets of HbA1c < 7%, blood pressure < 130/80 mmHg, and LDL cholesterol < 2.6 mmol/l., Conclusions: Almost half of the adult patients attending PHC clinics had undiagnosed T2D, or increased diabetes risk. Care practices, and achievement of treatment targets, were suboptimal.

New inhibitors of the bacterial transferase MraY are described. Their structure is based on an aminoribosyl-O-uridine like scaffold, readily obtained in two key steps. The amino group can be coupled with proline or guanylated. Alternatively, these amino, prolinyl or guanidinyl groups can be introduced through a triazole linker. Biological evaluation of these compounds on MraY from Bacillus subtilis revealed interesting inhibitory activity for both amino compounds., (Copyright 2010. Published by Elsevier Ltd.)

Muraymycin analogues with a lipophilic substituent were synthesized using an Ugi four-component assemblage. This approach provides ready access to a range of analogues simply by altering the aldehyde component. The impact of the lipophilic substituent on the antibacterial activity was very large, and analogues 7b-e and 8b-e exhibited good activity against a range of Gram-positive bacterial pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. This study also showed that the accessory urea-dipeptide motif contributes to MraY inhibitory and antibacterial activity. The knowledge obtained from our structure-activity relationship study of muraymycins provides further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on muraymycins.

The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7' or N(6') atom, were used to investigate the conformation-activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the (t)Bu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.

We investigated the specificity of interaction of a new type A lantibiotic, clausin, isolated from Bacillus clausii, with lipid intermediates of bacterial envelope biosynthesis pathways. Isothermal calorimetry and steady-state fluorescence anisotropy (with dansylated derivatives) identified peptidoglycan lipids I and II, embedded in dodecylphosphocholine micelles, as potential targets. Complex formation with dissociation constants of approximately 0.3 muM and stoichiometry of approximately 2:1 peptides/lipid intermediate was observed. The interaction is enthalpy-driven. For the first time, to our knowledge, we evidenced the interaction between a lantibiotic and C(55)-PP-GlcNAc, a lipid intermediate in the biosynthesis of other bacterial cell wall polymers, including teichoic acids. The pyrophosphate moiety of these lipid intermediates was crucial for the interaction because a strong binding with undecaprenyl pyrophosphate, accounting for 80% of the free energy of binding, was observed. No binding occurred with the undecaprenyl phosphate derivative. The pentapeptide and the N-acetylated sugar moieties strengthened the interaction, but their contributions were weaker than that of the pyrophosphate group. The lantibiotic decreased the mobility of the pentapeptide. Clausin did not interact with the water-soluble UDP-MurNAc- and pyrophosphoryl-MurNAc-pentapeptides, pointing out the importance of the hydrocarbon chain of the lipid target.

The WecA transferase is an integral membrane protein and a member of the polyprenyl phosphate N-acetylhexosamine-1-phosphate transferase superfamily. It initiates the biosynthesis of various bacterial cell envelope components such as the lipopolysaccharide O-antigen. We report on the first large-scale enzymatic synthesis, purification, and characterization of the undecaprenyl-pyrophosphoryl-N-acetylglucosamine product of the WecA transferase. This is an essential lipid intermediate for the biosynthesis of various bacterial cell envelope components. Its availability in a pure form will allow the biochemical and structural characterization of the various enzymes requiring it as a substrate for the synthesis of cell wall polymers.

To date, the structural and functional characterization of proteins belonging to the polyprenyl-phosphate N-acetylhexosamine-1-phosphate transferase superfamily has been relentlessly held back by problems encountered with their overexpression and purification. In the present work and for the first time, the integral membrane protein WecA that catalyzes the transfer of the GlcNAc-1-phosphate moiety from UDP-GlcNAc onto the carrier lipid undecaprenyl phosphate, yielding undecaprenyl-pyrophosphoryl-GlcNAc, the lipid intermediate involved in the synthesis of various bacterial cell envelope components, was overproduced and purified to near homogeneity in milligram quantities. An enzymatic assay was developed, and the kinetic parameters of WecA as well as the effects of pH, salts, cations, detergents, and temperature on the enzyme activity were determined. A minimal length of 35 carbons was required for the lipid substrate, and tunicamycin was shown to inhibit the enzyme at submicromolar concentrations.

The MraY transferase is an integral membrane protein that catalyzes an essential step of peptidoglycan biosynthesis, namely the transfer of the phospho-N-acetylmuramoyl-pentapeptide motif onto the undecaprenyl phosphate carrier lipid. It belongs to a large superfamily of eukaryotic and prokaryotic prenyl sugar transferases. No 3D structure has been reported for any member of this superfamily, and to date MraY is the only protein that has been successfully purified to homogeneity. Nineteen polar residues located in the five cytoplasmic segments of MraY appeared as invariants in the sequences of MraY orthologues. A certain number of these invariant residues were found to be conserved in the whole superfamily. To assess the importance of these residues in the catalytic process, site-directed mutagenesis was performed using the Bacillus subtilis MraY as a model. Fourteen residues were shown to be essential for MraY activity by an in vivo functional complementation assay using a constructed conditional mraY mutant strain. The corresponding mutant proteins were purified and biochemically characterized. None of these mutations did significantly affect the binding of the nucleotidic and lipidic substrates, but the k cat was dramatically reduced in almost all cases. The important residues for activity therefore appeared to be distributed in all the cytoplasmic segments, indicating that these five regions contribute to the structure of the catalytic site. Our data show that the D98 residue that is invariant in the whole superfamily should be involved in the deprotonation of the lipid substrate during the catalytic process.

The effect of xylazine (0.05 and 0.15 mg/kg, intramuscularly) on food (concentrate) intake was examined in ewes. Xylazine at 0.15 mg/kg significantly increased the 2 and 24 h food intake in comparison with control values. Xylazine treatments significantly and dose-dependently decreased the heart rate, respiratory rate and ruminal motility, and increased the rectal temperature when compared with pretreatment values. The changes in the physiological variables and the slight tranquilizing effect of xylazine apparently did not interfere with the food intake. The data suggest that xylazine increases food intake in freely feeding sheep.