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Sepsis-associated encephalopathy (SAE) induces neuroinflammation, which is associated with cognitive impairment (CI). CI is also correlated with aging. We used contrast-enhanced magnetic resonance imaging (MRI), perfusion MRI, and MR spectroscopy to assess long-term alterations in BBB permeability, microvascularity, and metabolism, respectively, in a rat lipopolysaccharide-induced SAE model. Free radical-targeted molecular MRI was used to detect brain radical levels at 24 h and 1 week post-LPS injection. CE-MRI showed increased Gd-DTPA uptake in LPS rat brains at 24 h in cerebral cortex, hippocampus, thalamus, and perirhinal cortex regions. Increased MRI signal intensities were observed in LPS rat brains in cerebral cortex, perirhinal cortex, and hippocampus regions 1 week post-LPS. Long-term BBB dysfunction was detected in the cerebral cortex at 6 weeks post-LPS. Increased relative cerebral blood flow (rCBF) in cortex and thalamus regions at 24 h, decreased cortical and hippocampal rCBF at 6 weeks, decreased cortical rCBF at 3 and 12 weeks, and increased thalamus rCBF at 6 weeks post-LPS, were detected. MRS indicated that LPS-exposed rat brains had decreased: NAA/Cho metabolite ratios at 1, 3, 6, and 12 weeks; Cr/Cho at 1, 3, and 12 weeks; and Myo-Ins/Cho at 1, 3, and 6 weeks post-LPS. Free radical imaging detected increased radical levels in LPS rat brains at 24 h and 1 week post-LPS. LPS-exposed rats were compared to saline-treated controls. We clearly demonstrated BBB dysfunction, impaired vascularity, and decreased brain metabolites, as measures of long-term neuroinflammatory indicators, as well as increased free radicals in a LPS-induced rat SAE model.

Objectives:: The purpose of this analysis was to evaluate sex differences in the rate of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) accrual in adults. Secondary analyses examined differences in the rate of VAT and SAT accrual in premenopausal, perimenopausal and postmenopausal women. Subjects/Methods:: Participants were 472 (60% female) non-Hispanic whites and aged 18–84 years at baseline in whom abdominal VAT and SAT were assessed using multiple-image magnetic resonance imaging at two time points, with an average follow-up of 7.3±2.6 years. Linear regression models were used to examine the effects of sex, baseline age and their interaction on rate of change per year in body composition measures (?BMI, ?VAT and ?VAT/SAT ratio (?VSR)) independent of baseline body composition measures, visit year, income, marital status, physical activity, smoking and alcohol intake. Secondary analyses examined differences in the rate of fat change by menopausal status (premenopausal, perimenopausal, postmenopausal). Results:: Levels of body mass index (BMI), VAT and VSR all increased over the 7-year period on average (P<0.001); however, the change in BMI (mean ?BMI=+0.5%) was far smaller than for VAT (mean ?VAT=+6.8%), SAT (mean ?SAT=+2.4%) and VSR (mean ?VSR=+3.6%). ?BMI, ?VAT and ?SAT decreased linearly with age in both sexes (P<0.01), such that older individuals had lower rates of BMI, VAT and SAT gain, and this deceleration in BMI, VAT and SAT accrual was greater in men than women (Pfor interaction <0.05). ?VSR did not vary with age in either sex but remained higher in men than women throughout adulthood. There were no differences in rate of weight or fat gain by menopausal status after adjustment for age. Conclusions:: Men and women continue to accrue abdominal adiposity with age, but the rate of weight and fat gain decreases over time, particularly in men.

Total gamma-glutamyl transferase and alkaline phosphatase, liver-specific alkaline phosphatase and high molecular weight forms of the two enzymes were measured in the sera of 42 patients with colorectal cancer, of whom 26 were apparently metastases-free and 16 had palpable liver metastases. The average levels of all enzymes were significantly higher in the group with metastases, but there was considerable overlap between the groups. The predictive values of positive results were of the order of 50-75%; predictive values of negative results were more than 70% for all tests, with high molecular weight alkaline phosphatase (87%) performing best in this respect. However, measurement of high molecular weight enzymes does not offer marked advantages over more conventional enzyme tests in the detection of hepatic metastases of colorectal cancer.

In a comparative study of serum and uterine tissue concentrations of cefoxitin and cefotaxime in patients undergoing hysterectomy, 40 patients were randomised to receive either cefoxitin 2g or cefotaxime 2g by intravenous administration. Serum samples were obtained before drug administration, at the ligation of the uterine arteries and at the end of surgery. Cefoxitin, cefotaxime and desacetylcefotaxime concentrations were determinedby high performance liquid chromatography. The composite serum halflives (determined by linear regression) for cefoxitin, cefotaxime and desacetylcefotaxime were 0.8, 0.7 and 2.1 hours, respectively. Although serum concentrations were higher for cefotaxime than for cefoxitin after a 2g dose, the uterine concentrations (at 40 mins) of cefoxitin were higher (51 μg/g vs 16 μg/g) than those of cefotaxime. After a 2g dose of cefotaxime the desacetylcefotaxime peak uterine concentration was 8 μg/g. Both drugs achieved adequate concentrations in serum and uterine tissue to prevent and treat infections caused by common Enterobacteriaceae such asEscherichia coli, with cefotaxime having a longer apparent duration of activity. However, cefoxitin provided serum and uterine concentrations above the minimum inhibitory concentration ofBacteroides fragilisfor a longer period than did cefotaxime.

Peptides with different chromatographic and electrophoretic properties were obtained from human placental and renal alkaline phosphatases by tryptic digestion of the enzymes labelled with radioactive orthophosphate at their active centres. These results provide structural evidence for the distinct genetic origins of the two isoenzymes that had previously been inferred from their different properties and from the observed phenotypic variation of placental phosphatase.

Hepatobiliary dysfunction in rheumatoid arthritis has been suggested on the basis of raised serum activity of alkaline phosphatase, 5-nucleotidase, lactic dehydrogenase and γ-glutamyl transferase, but a specific pathological lesion has not been demonstrated and serum transaminases and bilirubin are almost invariably normal. This paper reports a series of studies designed to determine the tissues of origin of the enzymes and offers an alternative interpretation of the enzymological findings. The results suggest that only alkaline phosphatase originates from the liver, while lactic dehydrogenase and 5-nucleotidase originate from synovial fluid polymorphs and synovial lining cells, respectively. Serum alkaline phosphatase may be induced by inflammatory mediators such as interleukin-1 because it correlates with the acute phase response. Serum lactic dehydrogenase is an integrated measure of polymorph lysis in all joints and offers a marker of joint inflammation more specific than measures such as the ESR. Levels of serum 5-nucleotidase provide information about the activity of the synovium. Finally, because hepatic necrosis does not normally occur, the transaminases may be used to monitor drug toxicity.