Linking [Fe(III)3] triangles with "double-headed"phenolic oximes.

The use of "double-headed" phenolic oximes produces a trigonal antiprismatic [Fe(III)(3)](2) cluster with an "internal cavity" filled with an additional Fe(3+) ion. Magnetic measurements reveal that the competition between different exchange interactions leads to a low-spin ground multiplet weakly separated in energy from a complex pattern of low-lying excited levels.

Association of PLOD1 polymorphisms with bone mineral density in a population-based study of women from the UK.

The PLOD1 gene is situated within a quantitative trait locus for regulation of bone mineral density (BMD) on chromosome 1p36 and is a strong functional candidate for the regulation of BMD and bone quality. PLOD1 encodes the enzyme procollagen-lysine, 2-oxoglutarate 5-dioxegenase (lysyl hydroxylase; EC 1.14.11.4), which catalyses the hydroxylation of lysine residues during the posttranslational modification of type I collagen, the major protein of bone. We investigated the role of PLOD1 as a genetic determinant of osteoporosis by studying two coding polymorphisms located in exon 3 of the PLOD1 gene in relation to BMD and bone loss in a population-based cohort of 678 Scottish women. We observed a significant association between lumbar spine (LS) BMD and a polymorphism at nucleotide 386 (G386A) of PLOD1, which results in an alanine-threonine amino acid change at codon 99 (A99T). Heterozygotes for G386A had significantly reduced LS-BMD when compared with the other genotype groups, and the difference remained significant after correcting for confounding factors. A similar association was observed between LS-BMD and a conservative polymorphism at position 385 (C385T), but this was in strong linkage disequilibrium (LD) with G386A. There was no evidence for an allele dose effect for either polymorphism, and the strongest association was observed in heterozygotes. No association was found between PLOD1 alleles and femoral-neck BMD or bone loss, but the hydroxylysylpyridinoline to lysylpyridinoline ratio was significantly increased in G386A heterozygotes compared with other genotype groups, suggesting a functional effect of this polymorphism on enzyme activity. Our findings show that heterozygosity for the A99T variant of PLOD1 is associated with reduced LS-BMD and an altered ratio of hydroxylysylpyridinoline to lysylpyridinoline. Whilst further studies will be required to confirm and extend these observations, our studies raise the possibility that A99T heterozygosity might affect lysyl hydroxylase function and regulate bone mass.

Molecular dynamics simulations to aid the rational design of organic friction modifiers.

Molecular dynamics simulations were performed under conditions of constant volume and temperature and of constant pressure and temperature to elucidate the structure activity relationships of a series of non-ionic surfactant molecules derived from vegetable fat and employed as friction modifiers in commercial engine oils. The simulations show the extent to which intermolecular hydrogen bonding is important in determining the stability of the monolayer formed by the surfactant molecules and show that mono-alkanoyl glyceride molecules are able to pack more efficiently, forming significantly more intermolecular hydrogen bonds and occupying approximately half the volume needed by di-alkanoyl glyceride molecules. Density profiles are presented which show significant mixing of the hydrophobic tail groups and a non-polar solvent. The distribution of torsion angles in the tail groups shows that the conformation is consistent with a liquid at finite temperature rather than a crystal structure. The measured friction coefficients of equimolar solutions of the glycerides show that the efficacy as friction modifiers varies in the order mono-, di- and the tri-oleyl glyceride, which is consistent with the efficacy of film formation predicted by the molecular dynamics calculations.

Expression and distribution of InsP(3) receptor subtypes in proliferating vascular smooth muscle cells.

The expression and distribution of types 1, 2, and 3 inositol 1,4, 5-trisphosphate receptor (InsP(3)R) in proliferating, primary cultures of rat aortic smooth muscle were compared to fully developed and differentiated rat aortic smooth muscle. Subtype-specific InsP(3)R antibodies revealed that the expression of type 1 InsP(3)R was similar in cultured aortic cells and aorta homogenate but expression of type 2 and 3 InsP(3)R subtypes was increased 3-fold in cultured aortic cells. The distribution of the type 1 InsP(3)R was located throughout the cytoplasm; type 2 InsP(3)R was found closely associated with the nucleus and at the plasma membrane; type 3 InsP(3)R was distributed predominantly around the nucleus. Alterations in InsP(3)R subtype expression and localization may have important functions in regulating intracellular calcium release around the nucleus when vascular smooth muscle cells switch to a more proliferating phenotype.

Expression and distribution of the type 1 and type 3 inositol 1,4, 5-trisphosphate receptor in developing vascular smooth muscle.

The recent discoveries of inositol 1,4,5-trisphosphate (IP3) receptor subtypes with different affinities for IP3 and their potential involvement in development has important consequences for vascular smooth muscle. This study has examined the expression and distribution of the type 1 and type 3 IP3 receptor subtypes in developing rat vascular smooth muscles. Immunoblotting of portal vein and aorta from neonatal (2 to 4 days) and fully developed (6 weeks) rats revealed significantly higher levels of the type 3 IP3 receptor expression in neonatal, compared with developed, vascular smooth muscles. In contrast, expression of the type 1 IP3 receptor in neonates was lower compared with developed vascular smooth muscles. Immunolocalization of the type 3 IP3 receptors in neonatal tissues revealed that staining corresponded to the distribution of the sarcoplasmic reticulum (visualized by osmium ferricyanide staining of thin tissue sections), which suggested localization of the type 3 IP3 receptor throughout the sarcoplasmic reticulum network. We conclude that type 3 IP3 receptors are the predominant subtype in the development of vascular smooth muscle and are distributed throughout the sarcoplasmic reticulum in these cells. The switch in isoforms of the IP3 receptor during development from the type 3 with low affinity for IP3 to the higher-affinity type 1 receptor may play a role in calcium-mediated regulation of developing vascular smooth muscle.

Surface coordination chemistry: corrosion inhibition by tetranuclear cluster formation of iron with salicylaldoxime.

A tetranuclear iron cluster is the principal component of the purple coatings produced by treating a mild steel surface with a salicylaldoxime corrosion inhibitor. This was shown by comparison of the spectroscopic data with those of the cluster [{Fe(salH)(HsalH)}4 ], which was obtained from FeCl3 and salicylaldoxime (H2 salH) and has a distorted tetrahedral arrangement of Fe(III) atoms coordinated by terminal (1-) and bridging (2-) salicylaldoximate ligands (the central core of the cluster is depicted).

The organization of successful diabetes management in primary care.

The following article represents a personal view on the crucially important factors necessary for successful diabetes management in primary care. It stresses the flexibility of approach and the ongoing dynamic aspects of care, emphasizing the importance of team effort, recognizing the person with diabetes as an integral member of the team.

Audit of the care of patients with epilepsy in general practice.

BACKGROUND: Previous studies have shown that there is great potential for improving the management of patients with epilepsy. AIM: To identify all patients with epilepsy, to evaluate and audit their care in relation to an annual review, to document seizure frequency and appropriateness of daily therapy to aid compliance and to propose strategies to improve these and other aspects of epileptic care. METHOD: An audit of the care of patients with epilepsy was undertaken in two King's Lynn practices with a combined population of 22,500. Principles for the management of epilepsy were established. From these principles, the following standards were agreed: 75% of patients on treatment for epilepsy should be seen every year, 75% of patients should have their seizure frequency documented, and 75% of patients should take their anti-epileptic drugs no more than twice daily. As a result of the first audit cycle, changes were made in the documentation and advice regarding treatment relating to these standards. RESULTS: The first audit cycle showed that 83% of patients had been seen at least once in the previous year, that documentation of seizure frequency existed for 51% of patients in the past year, and that 63% of patients were taking their treatment no more than twice daily. The evaluation was repeated 22 months later and an overall improvement was demonstrated in the first two results: 95% of patients had been seen in the past year, 93% had had their seizure frequency documented; however, only 66% of patients were taking their treatment twice daily or less. CONCLUSION: Call and recall, and documentation of seizure frequency were improved by this clinical audit. However, alterations in daily therapy appeared difficult for a variety of reasons; for example, therapy might have been initiated by a hospital specialist, and patients in a stable condition might have been apprehensive about changes. In order to improve the care of patients with epilepsy, a primary care team approach is desirable within a structure of good specialist services.

Isoelectric focusing in an immobilized pH gradient for the detection of intrathecal IgG in cerebrospinal fluid: sensitivity and specificity for the diagnosis of multiple sclerosis.

Cerebrospinal fluid and serum from 192 patients was analysed for the presence of intrathecally synthesized oligoclonal IgG bands using isoelectric focusing in an immobilized pH gradient pH 7-10. The sensitivity of this method for the diagnosis of multiple sclerosis (MS) was 95% (21 of 22), or 75% if patients with suspected MS were included. The specificity for the diagnosis of MS was 98%, or 96% if the suspected MS patients were included. The very high specificity may be because the intrathecally synthesized oligoclonal IgG associated with MS is more alkaline than IgG from serum and is better detected in an immobilized alkaline pH gradient.

Two-hour assay for lutropin during ovulation.

A rapid lutropin assay with a 2-h incubation time and a second antibody/polyethylene glycol separation step is presented. Assay time is shortened by incubating at 37 degrees C and using relatively high concentrations of antibody and radioligand. The interval required for the antigen/antibody reaction varies directly with lutropin concentration, from 1 h for ovulation values to 8 h for low values. After a 2-h incubation, low concentrations have reached 80% of their equilibrium concentration. Separation of the bound fraction by use of combined second antibody/polyethylene glycol (50 g/L) gave one-third the nonspecific binding and as rapid a separation as with polyethylene glycol (180 g/L) alone. Optimal conditions for separating the immune complex were established, and separation was found to be independent of protein concentrations in urine or serum. This tested assay can detect increasing and ovulatory lutropin concentrations in urine or serum, but with some sacrifice in sensitivity.

Comparative double-blind study of cephalexin and co-trimoxazole in urinary tract infections.

Treatment with cephalexin 1 g twiec daily and cotrimoxazole 2 tablets twice daily was compared in a double-blind, randomised study of 100 women with urinary tract infections. CO-trimoxazole gave a significantly higher cure rate compared with cephalexin two and six weeks after the one-week course of treatment. The higher failure rate with cephalexin was not related to the age of the patient, presentation, pyelographic appearances, or type of organism in the initial infection. Among the failures all but one of the organisms were sensitive to cephalexin. With the dosage regimen and duration of treatment used in this study cotrimoxazole appears to be superior to cephalexin in the management of acute urinary infections.

Use of co-trimoxazole in chronic renal failure.

Twenty patients with chronic renal failure and either urinary or respiratory tract infection were treated with co-trimoxazole. Seventeen patients showed no deterioration in renal function while receiving co-trimoxazole. Deterioration in renal function during treatment in the other three patients was due to factors other than administration of the drug. It is concluded that co-trimoxazole can be used in patients with chronic renal failure provided the dose is adjusted according to the degree of renal failure.