Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells

Antioxidant preservatives prolong the quality of food and ensure the nutritional adequacy, palatability and safety of many processed foods and beverages. Effects of sodium sulfite (E221) and sorbic acid (E200) were investigated in human peripheral blood mononuclear cells (PBMC) which were purified from blood of healthy donors. Cells were stimulated with the mitogen phytohaemagglutinin in vitro, which induces proliferation of T-cells and the production of Th1-type cytokines like interferon-γ. The latter triggers enzyme indoleamine (2,3)-dioxygenase, which degrades tryptophan, and GTP cyclohydrolase I, which leads to increased neopterin production, in monocyte-derived macrophages. Sodium sulfite and sorbic acid suppressed both these biochemical changes in a dose-dependent way (P < 0.01 at 1 mM sodium sulfite and 50 mM sorbic acid). Data demonstrate a suppressive influence of sodium sulfite and sorbic acid on the activated Th1-type immune response.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.     

A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids.

A combined LC/RIA procedure is described for the selective determination of dexamethasone (DEX) and its prodrug dexamethasone-21-isonicotinate (DIN) in plasma. The low affinity of the employed dexamethasone antiserum for DIN (cross-reactivity less than 0.5%) allowed the direct determination of DEX in plasma extracts. For the determination of DIN, both substances of interest were separated by LC, the DIN containing fraction was collected, hydrolysed and the generated DEX was consequently assayed by radioimmunoassay. The assay detection limits were 0.1 ng ml-1 for DEX and 0.75 ng ml-1 for DIN. For both substances, inter- and intra-day variabilities (RSDs) were 6 and 12%, respectively.     

Analysis of the interbeat interval increment to detect obstructive sleep apnoea/hypopnoea.

The prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is underestimated and its diagnosis is costly and restricted to specialised sleep laboratories. The frequency component of interbeat interval increment (III) has been proposed as a simple and inexpensive diagnostic tool in OSAHS. In a set of 150 patients with clinically suspected sleep-related breathing disorder, the actual predictive accuracy of the power spectral density of the III of the very low frequencies (%VLFI) was analysed by comparing with the apnoea/hypopnoea index (AHI), as assessed by synchronised polysomnography. OSAHS was defined in 100 patients according to an AHI>or=15 events.h(-1). Receiver operator characteristic curves built for %VLFI confirmed that this variable was able to separate OSAHS positive from OSAHS negative with statistical significance. Using an appropriate threshold (>4%), %VLFI demonstrated a positive predictive value of 80%. Misclassification of false-positive subjects occurred when the patient presented significant sleep discontinuity and sleep fragmentation (sleep fragmentation index>or=50 events.h(-1)) related to insomnia or periodic limb movements. A power spectral density of the interbeat interval increment of very low frequencies>4% allowed correct classification of obstructive sleep apnoea/hypopnoea syndrome when the clinical history suggested sleep-related breathing disorders and when moderate-to-severe cases are considered. Higher power spectral density of the interbeat interval increment of very low frequencies may also indicate disrupted sleep in the absence of clear clinical symptoms of sleep apnoea/hypopnoea syndrome.     

Amnesic Concentrations of the Nonimmobilizer 1,2-Dichlorohexafluorocyclobutane (F6, 2N) and Isoflurane Alter Hippocampal θ Oscillations In Vivo

Background: Drug-induced temporary amnesia is one of the principal goals of general anesthesia. The nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also termed 2N) impairs hippocampus-dependent learning at relative, i.e., lipophilicity-corrected, concentrations similar to isoflurane. Hippocampal [theta] oscillations facilitate mnemonic processes in vivo and synaptic plasticity (a cellular model of memory) in vitro and are thought to represent a circuit level phenomenon that supports memory encoding. Therefore, the authors investigated the effects of F6 and isoflurane on [theta] oscillations (4-12 Hz).

Methods: Thirteen adult rats were implanted with multichannel depth electrodes to measure the microelectroencephalogram and were exposed to a range of concentrations of isoflurane and F6 spanning the concentrations that produce amnesia. Five of these animals also underwent control experiments without drug injection. The authors recorded the behavioral state and hippocampal field potentials. They confirmed the electrode location postmortem by histology.

Results: The tested concentrations for isoflurane and F6 ranged from 0.035% to 0.77% and from 0.5% to 3.6%, respectively. Isoflurane increased the fraction of time that the animals remained immobile, consistent with sedation, whereas F6 had the opposite effect. Electroencephalographic power in the [theta] band was less when the animals were immobile than when they explored their environment. F6 suppressed the power of oscillations in the [theta] band. Isoflurane slowed [theta] oscillations without reducing total power in the [theta] band.     

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.