Structure of UDP-N-acetylglucosamine enolpyruvyl transferase, an enzyme essential for the synthesis of bacterial peptidoglycan, complexed with substrate UDP-N-acetylglucosamine and the drug fosfomycin.

BACKGROUND: UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), catalyses the first committed step of bacterial cell wall biosynthesis and is a target for the antibiotic fosfomycin. The only other known enolpyruvyl transferase is 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, an enzyme involved in the shikimic acid pathway and the target for the herbicide glyphosate. Inhibitors of enolpyruvyl transferases are of biotechnological interest as MurA and EPSP synthase are found exclusively in plants and microbes. RESULTS: The crystal structure of Escherichia coli MurA complexed with UDP-N-acetylglucosamine (UDP-GlcNAc) and fosfomycin has been determined at 1.8 A resolution. The structure consists of two domains with the active site located between them. The domains have a very similar secondary structure, and the overall protein architecture is similar to that of EPSP synthase. The fosfomycin molecule is covalently bound to the cysteine residue Cys115, whereas UDP-GlcNAc makes several hydrogen-bonding interactions with residues from both domains. CONCLUSIONS: The present structure reveals the mode of binding of the natural substrate UDP-GlcNAc and of the drug fosfomycin, and provides information on the residues involved in catalysis. These results should aid the design of inhibitors which would interfere with enzyme-catalyzed reactions in the early stage of the bacterial cell wall biosynthesis. Furthermore, the crystal structure of MurA provides a model for predicting active-site residues in EPSP synthase that may be involved in catalysis and substrate binding.

Nutrition, anaemia, geohelminth infection and school achievement in rural Jamaican primary school children.

OBJECTIVE: To determine whether nutritional status, anaemia and geohelminth infections were related to school achievement and attendance in Jamaican children. DESIGN: A cross-sectional study using a randomly selected sample. SUBJECTS: Eight hundred children aged 9-13 y randomly selected from those enrolled in grade 5 in 16 primary schools in rural Jamaica. RESULTS: The mean height-for-age of the children was -0.37 z-score +/- 1.0 s.d. with 4.9% having heights-for-age < -2 s.d. of the NCHS references. Anaemia (Hb < 11 g/dl) was present in 14.7% of the children, 38.3% were infected with Trichuris trichiura and 19.4% with Ascaris lumbricoides. Achievement levels on the Wide Range Achievement Test were low, with children performing at grade 3 level. In multilevel analyses, controlling for socioeconomic status, children with Trichuris infections had lower achievement levels than uninfected children in spelling, reading and arithmetic (P < 0.05). Children with Ascaris infections had lower scores in spelling and reading (P < 0.05) Height-for-age (P < 0.01) was positively associated with performance in arithmetic. Ascaris infection (P < 0.001) and anaemia (P < 0.01) predicted poorer school attendance. CONCLUSION: Despite mild levels, undernutrition and geohelminth infections were associated with achievement, suggesting that efforts to increase school achievement levels in developing countries should include strategies to improve the health and nutritional status of children.

PIP: The association of nutritional status, anemia, and geohelminth infection with school attendance and performance was investigated in a cross-sectional study of 800 primary school students 9-13 years of age (mean age, 10.8 years) from 4 rural parishes in Jamaica. 4.9% of the children had heights-for-age less than 2 standard deviations of the US National Center for Health Statistics references and 14.7% were anemic; 38.3% were infected with Trichuris trichiura and 19.4% with Ascaris lumbricoides. Multivariate analyses, controlled for socioeconomic status, indicated children with Trichuris infection had significantly lower achievement levels than uninfected children in spelling, reading, and arithmetic, while those with Ascaris infection had significantly lower scores in spelling and reading. Height-for-age was positively associated with performance in arithmetic. Ascaris infection and anemia predicted poorer school attendance. The associations demonstrated in this study are not necessarily causal. However, these findings indicate that efforts to increase school achievement levels in developing countries should include strategies to address the health and nutritional status of rural children.

The nutritional status of rural Jamaican school children.

Three thousand, eight hundred and eighty-two (3,882) children in grades 2-5, attending 16 rural primary and all-age schools in central Jamaica were weighed and their weight-for-age standard deviation scores calculated using the World Health Organization/National Center for Health Statistics (WHO/NCHS) references. Heights were also measured in a random sample of the grade 5 children (n = 793) and height-for-age and body mass index (BMI-kg/m2) calculated. Sixty-nine per cent of the total sample were of normal weight-for-age, 2% were moderately undernourished (weight-for-age > -3 Z-score, < or = -2 Z-score), and a further 24% mildly undernourished (weight-for-age > -2 Z-score, < or = -1 Z-score). Few children were overweight. The frequency distribution of weight-for-age was similar in girls and boys. In the subsample of children in whom heights were measured, 25.8% were < or = -1 Z-score height-for-age, and of these 4.9% were < -2 Z-score. Compared with a survey conducted in a similar rural area in the 1960s, the children's mean weights for age group categories were 1.1 to 3.7 kg heavier. Children who were older than appropriate for their grade were more likely to be undernourished (Odds ratio 3.94, 95% CI 3.21, 4.83), which suggests that undernourished children may be more likely to repeat a grade or start school later.

Zingiber officinale (ginger)--an antiemetic for day case surgery.

The effect of powdered ginger root was compared with metoclopramide and placebo. In a prospective, randomised, double-blind trial the incidence of postoperative nausea and vomiting was measured in 120 women presenting for elective laparoscopic gynaecological surgery on a day stay basis. The incidence of nausea and vomiting was similar in patients given metoclopramide and ginger (27% and 21%) and less than in those who received placebo (41%). The requirement for postoperative antiemetics was lower in those patients receiving ginger. The requirements for postoperative analgesia, recovery time and time until discharge were the same in all groups. There was no difference in the incidence of possible side effects such as sedation, abnormal movement, itch and visual disturbance between the three groups. Zingiber officinale is an effective and promising prophylactic antiemetic, which may be especially useful for day case surgery.

Adrenaline-induced hypotension in neurosurgery.

We have compared the effects of scalp infiltration with 0.5% lignocaine, 0.5% lignocaine with adrenaline 1:200,000, 0.9% saline and 0.9% saline with adrenaline 1:200,000, in a prospective, randomized, double-blind study. Direct arterial pressure, heart rate and bleeding at incision were recorded in 80 patients undergoing craniotomy or craniectomy. Arterial pressure decreased by more than 20% from preinfiltration values in 40% of patients in the saline with adrenaline group, and in 55% of patients in the lignocaine with adrenaline group. It did not decrease in patients who did not receive adrenaline.

Schoolchildren's diets and participation in school feeding programmes in Jamaica.

OBJECTIVES: To describe food consumption during the school day of rural Jamaican children and participation in two government school feeding programmes. To determine factors which were related to these. DESIGN: Cross sectional. SETTING: 16 primary schools in rural Jamaica. SUBJECTS: 415 children in grades 2 and 5 (ages 7 and 10 years). RESULTS: Consumption of sweets, sweet drinks and snacks was high. Mean intakes at lunch were: energy 1537 kJ (SD 756), protein 10.4 g (SD 7.6) and iron 1.5 mg (SD 1.2). The mean energy intake was 17-20% of the daily requirement for this age group. Two types of school feeding programmes were available in the schools, one provided a cooked meal and the other a bun and milk. Median availability of school meals (as a percentage of children enrolled in the schools) over three terms was 24.6% (range 0-85.4%). Twenty per cent of the children participated in one or other programme. Poorer children were more likely to participate in the bun and milk programme (odds ratio 2.1, 95% CI 1.3-3.5) but children with more money to purchase food participated in the more costly cooked meal programme (odds ratio 2.4, 95% CI 1.3-4.6). CONCLUSIONS: Energy intakes at lunch in Jamaican children were somewhat below optimal levels and the reliance on sweets and snacks is an area of concern. Programme characteristics such as meal cost, may affect access to school feeding by poor children.

The nutritional status of rural Jamaican school children

Three thousand, eight hundred and eighty-two (3,882) children in grades 2-5, attending 16 rural primary and all-age schools in central Jamaica were weighed and their weight-for-age standard deviation scores calculated using the World Health Organization/National Center for Health Statistics (WHO/NCHS) references. Heights were also measured in a random sample of the grade 5 children (n = 793) and height-for-age and body mass index (BMI-kg/m2) calculated. Sixty-nine per cent of the total sample were of normal weight-for-age, 2were moderately undernourished (weight-for-age > -3 Z-score, -2 Z-score, < or = -1 Z-score). Few children were overweight. The frequency distribution of weight-for-age was similar in girls and boys. In the subsample of children in whom heights were measured, 25.8were < or = -1 Z-score height-for-age, and of these 4.9were < -2 Z-score. Compared with a survey conducted in a similar rural area in the 1960s, the children's mean weights for age group categories were 1.1 to 3.7 kg heavier. Children who were older than appropriate for their grade were more likely to be undernourished (Odds ratio 3.94, 95CI 3.21, 4.83), which suggests that undernourished children may be more likely to repeat a grade or start school later.