Proton magnetic resonance spectroscopy of brain metabolic shifts induced by acute administration of 2‐deoxy‐d‐glucose and lipopolysaccharides

In vivo proton magnetic resonance spectroscopy (¹H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro‐inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2‐deoxy‐d ‐glucose (2DG) reduced the levels of gamma‐aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N‐acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) – a very common pro‐inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro‐inflammatory stimuli can explain the contradictory results of the brain ¹H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA. Copyright © 2014 John Wiley & Sons, Ltd.     

Decreased Beta-Carotene Levels in Exfoliated Vaginal Epithelial Cells in Women With Vaginal Candidiasis

PROBLEM: Women are more susceptible to vaginal candidiasis when the host immune response is suppressed. The antioxidant nutrient beta-carotene is postulated to possess immunoenhancing properties. The purpose of this study was to investigate beta-carotene concentrations in exfoliated vaginal epithelial (EVE) cells in women with vaginal candidiasis. METHODS: Beta-carotene levels in EVE cells, collected by a saline lavage technique from 22 women with vaginal candidiasis and 20 normal controls, were analyzed. The diagnosis of vaginal candidiasis was established by the presence of pruritus, white cheesy vaginal discharge, and a positive potassium hydroxide preparation. Beta-carotene levels were assayed using high pressure liquid chromatography. RESULTS: Vaginal cell concentrations of beta-carotene were significantly decreased in women with vaginal candidiasis (P < 0.001). CONCLUSIONS: Decreased beta-carotene levels, and possibly other antioxidants, may alter the local immune response resulting in disturbances in the vaginal flora, overgrowth of Candida, and the development of vaginal candidiasis.     

Using a hand-held spirometer as a monitoring tool in chronic theophylline therapy

This study evaluates the use of a hand-held spirometer (pocket spirometer, Buhl type) in monitoring pulmonary function as a part of a homebased pharmacokinetic service for patients with respiratory disease. To calibrate the spirometer and determine its accuracy, six healthy volunteers were trained in its use by the pharmacist. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were determined for each volunteer once a month for six months. The T test for the presence of outliers showed no statistical difference at p less than 0.05. Seven patients on chronic therapy with theophylline derivatives for respiratory problems were randomly referred by their physicians to the pharmacokinetic service. The pharmacist counseled each patient and measured FVC and FEV1 once a month for six months. The ratio, (FEV1:FVC) X 100, was calculated for each patient before and after steady-state serum level determination and dosage adjustment. The mean value for this ratio was 45.1 before pharmacokinetic intervention and 57.5 after intervention. Using the Student's t-test, these results were significant (p less than 0.05). The correlation coefficient was calculated to determine if a correlation existed between the increase in the ratio and the increase in serum theophylline levels. Serum levels were ordered before and after intervention for five of the seven patients receiving pharmacokinetic intervention. The change in serum levels vs. change in the ratio was associated with a correlation coefficient of 0.718. Monitoring pulmonary function may be a useful adjunct for the pharmacist who provides pharmacokinetic counseling to patients with respiratory disease, but expanded studies are needed to judge the value of routine spirometric measurements on homebased patients.     

Effects of systemic or oral ad libitum monosodium glutamate administration on striatal glutamate release, as measured using microdialysis in freely moving rats

We examined effects of high doses of monosodium glutamate (MSG) on extracellular glutamate levels in rat striata, using in vivo microdialysis. Parenteral doses (0.5, 1.0 and 2.0, but not 0.25, g/kg, i.p.) caused dose- and time-dependent increases, peaking after 40 min (at 174 ± 47%, 485 ± 99% and 1021 ± 301% of basal levels, respectively). In contrast, dietary MSG (1.49 ± 0.10 g/kg/h) was ineffective.     

Chronic Salmonella bacteriuria with intermittent bacteremia treated with low doses of amoxicillin or ampicillin.

Amoxicillin and ampicillin were compared at a dose of 250 mg twice daily for 4 weeks to treat Salmonella typhi or Salmonella paratyphi A chronic bacteriuria with intermittent bacteremia. Eleven patients received amoxicillin, and 15 received ampicillin. Concentrations of the two drugs were measured in the urine and serum on treatment days 1, 2, and 7. The urine levels of both antibiotics were maximal 2 h after administration, and minimal levels were 80-fold higher than the S. typhi minimal inhibitory concentration and 20-fold higher than the S. paratyphi A minimal inhibitory concentration. The serum level of amoxicillin was below the minimal inhibitory concentration of S. paratyphi A 6 h after administration on each of the testing days. The serum antibiotic levels of the two drugs showed no cumulative effect at day 2 or day 7. Of the 11 patients treated with amoxicillin, 1 had positive urine cultures during treatment, and 1 treated with ampicillin continued to be symptomatic.. Recurrence of bacteriuria occurred in three of seven patients with persistent bladder calcification. None of the 26 patients in this study had positive blood culture during or after treatment. Amoxicillin and ampicillin at a dose of 250 mg twice daily were equally successful in treating chronic salmonelluria.