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Reduction of virus shedding by B. bifidum in experimentally induced MRV infection. Statistical application for ELISA.

The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine group A rotavirus (MRV) was examined in the intestines of BALB/c infected mice. In experiments designed to determine whether B. bifidum mediated MRV shedding during diarrheal disease, pregnant dams (and their expected litters) were randomly assigned to the following groups: (1) mice infected with MRV alone; (2) B. bifidum-treated + MRV-infected mice; (3) B. bifidum-treated controls; and (4) saline control animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of group A rotavirus was used to measure virus protein. The sensitivity of the MRV antigen detector ELISA was determined by serially diluting the rotavirus antigen in test samples. Antigen was detected in dilution ranges of 1:256-1:4096 during the acute phase and 1:16-1:512 in the recovery phase of MRV clinical disease, in the samples tested. Treatment with B. bifidum significantly reduced shedding of MRV antigen (P < 0.009) on days 2-10 postinoculation. The reduction in shedding of virus protein corresponded well with delayed onset of acute diarrhea (P < 0.02). Closer examination of tissue cross sections under electron microscopy revealed that the B. bifidum-ingested strain adhered to the epithelium of the small intestine. These results suggest that priming the intestine with B. bifidum is effective against experimental MRV challenge and confirmed the potential usefulness of this detector ELISA for studying the kinetics of group A rotavirus infection in animals and humans.

Animals↗

Derangement in aerobic and anaerobic energy metabolism in skeletal muscle of critically ill and recovering rats.

As part of our research into the mechanisms of protein wasting and muscle weakness during critical illness, we here investigate various aspects of energy metabolism. Intraperitoneal injection of zymosan in rats leads to an acute phase of critical illness followed by a prolonged recovery phase. Previously we observed low activities of mitochondrial enzymes, reduced protein synthesis rates and low concentrations of glutamine in skeletal muscle of zymosan-treated rats. In the present study we investigated (1) whether decreases in high energy phosphates are present in skeletal muscle of these rats and (2) whether an impairment in the glycolytic pathway or the tricarboxylic acid cycle leads to these decreases. Concentrations of creatine phosphate and ATP were decreased in zymosan-treated rats to approx. 85% of pair-fed control values respectively on day 2 and on days 4 and 6 after treatment. Concentrations of tricarboxylic acid (TCA) cycle intermediates were decreased to 80% on day 6 after zymosan treatment. Lactate/pyruvate ratio and concentrations of lactate and glycogen were normal at all sampling times. We conclude that no major changes in concentrations of high energy phosphates and in concentrations of intermediates of TCA cycle, glycolysis and glycogenolysis were present. This indicated that, although the maximal oxidative capacity (mitochondrial content) is decreased, no derangement in energy metabolism seems to be present in skeletal muscle of critically ill and recovering rats.

Adenine Nucleotides↗

Attacks of anxiety, panic and frenzy, and their related depression: a hypothesis.

The hypothesis is that the pathogenesis of attacks of anxiety, panic or frenzy (hyperactive disorders) rests on the abnormal activation of the same brain-controlled survival mechanism, and that the subsequent depression is part of this nosological continuum. The acute activation phase would be the counterpart of two principal types of reaction to threat and imminent attack: run-for-life or fight-for-life, sub-served by brain-controlled metabolic activation to make energy available for either. The phase of depression that follows would represent the recovery phase during which homeostatic controls and metabolism, distorted during the acute attacks, are restored to normal. It is further tentatively postulated that anxiety and panic attacks may mimic run-for-life responses, whereas attacks of frenzy might be homologous to fight-for-life. Both the degree of dys-homeostasis and the completeness of the return to normality through the depression phase would depend on severity, duration and, importantly, spacing of the acute attacks. At the limit, severity, long duration and only short intermissions between hyperactive attacks may be postulated to result in persistence of the depression.

Anxiety Disorders↗

Interaction between nutrition and Eimeria acervulina infection in broiler chickens: development of an experimental infection model.

In three experiments broiler chickens were inoculated with sporulated Eimeria acervulina oocysts at 18 d of age. Feed intake, body-weight gain, brush-border enzyme activities, fat digestion, protein digestion and protein retention were measured. Body-weight gain was reduced during the acute phase of the infection and increased during the recovery phase of the infection. Feed intake was decreased on day 4 and day 5 postinfection (PI) and increased from day 7 to day 11 PI. Maltase (EC 3.2.1.20) and sucrase (EC 3.2.1.48) activities were decreased on day 5 PI in all intestinal segments. In Expts 2 and 3, however, maltase activity was increased in the ileum. Fat digestion was decreased from day 2 to day 11 PI. N digestion and retention were decreased from day 2 to day 11 PI.

Animal Nutritional Physiological Phenomena↗

Identification and characterization of a cytotoxic T cell epitope of hepatitis C virus presented by HLA-B*3501 in acute hepatitis.

In order to clarify the role of cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) infection, an HLA-B35-restricted cytotoxic T cell epitope of HCV was identified using a strategy called reverse immunogenetics. Twenty-eight of 53 HCV peptides carrying two anchor residues were selected as HLA-B*3501 binding peptides. These peptides were used to induce the specific cytotoxic T cells in peripheral blood lymphocytes from a patient with acute hepatitis C. Six HLA-B*3501 binding peptides induced the peptide-specific CTL. One (HPNIEEVAL) of five peptides was confirmed as the epitope by the specific T cell clones. A sequence identical to the epitope was detected in isolates of the virus from the patient and a strong CTL response to this epitope was observed in the acute phase of hepatitis C but not in the recovery phase. The specific CTL for this epitope were not detected in peripheral blood lymphocytes from patients with chronic hepatitis C. Together these results suggest that the CTL specific for this epitope have an important role in the elimination of the virus in the patient.

Acute Disease↗

Traffic lights in trichodesmium. Regulation of photosynthesis for nitrogen fixation studied by chlorophyll fluorescence kinetic microscopy.

We investigated interactions between photosynthesis and nitrogen fixation in the non-heterocystous marine cyanobacterium Trichodesmium IMS101 at the single-cell level by two-dimensional (imaging) microscopic measurements of chlorophyll fluorescence kinetics. Nitrogen fixation was closely associated with the appearance of cells with high basic fluorescence yield (F(0)), termed bright cells. In cultures aerated with normal air, both nitrogen fixation and bright cells appeared in the middle of the light phase. In cultures aerated with 5% oxygen, both processes occurred at a low level throughout most of the day. Under 50% oxygen, nitrogen fixation commenced at the beginning of the light phase but declined soon afterwards. Rapid reversible switches between fluorescence levels were observed, which indicated that the elevated F(0) of the bright cells originates from reversible uncoupling of the photosystem II (PSII) antenna from the PSII reaction center. Two physiologically distinct types of bright cells were observed. Type I had about double F(0) compared to the normal F(0) in the dark phase and a PSII activity, measured as variable fluorescence (F(v) = F(m) - F(0)), similar to normal non-diazotrophic cells. Correlation of type I cells with nitrogen fixation, oxygen concentration, and light suggests that this physiological state is connected to an up-regulation of the Mehler reaction, resulting in oxygen consumption despite functional PSII. Type II cells had more than three times the normal F(0) and hardly any PSII activity measurable by variable fluorescence. They did not occur under low-oxygen concentrations, but appeared under high-oxygen levels outside the diazotrophic period, suggesting that this state represents a reaction to oxidative stress not necessarily connected to nitrogen fixation. In addition to the two high-fluorescence states, cells were observed to reversibly enter a low-fluorescence state. This occurred mainly after a cell went through its bright phase and may represent a fluorescence-quenching recovery phase.

Chlorophyll↗

Analysis and Characterization of 3-(3,4-Dichlorophenyl)-1,1-Dimethylurea (DCMU)-resistant Euglena: I. Growth, Metabolic and Ultrastructural Modifications during Adaptation to Different Doses of DCMU.

Cultures of Euglena gracilis Klebs strain Z Pringsheim were grown photoorganotrophically in the presence of different concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) in the range of 0.05 to 250 micromolar. Cultures were serially transferred and various metabolic parameters were followed for 10 weeks. A process of adaptation occurred which was divided operationally into three phases. A phase of ultrastructural disorganization occurred, succeeded by a recovery phase; their intensity and duration were functions of the dose of DCMU. A stable adaptation phase then ensued. This phase was observed in all cultures except that exposed to the highest DCMU concentration. Adapted cells from all of the DCMU cultures contained twice the protein and half the paramylon of the control cells and thus utilized the carbon source to accumulate cellular reserves with only half the efficiency of controls. DCMU affected cellular metabolism as well as photosynthesis.The energy charge remained at high levels throughout adaptation, although the size of the adenylate pool was half that of controls at the disorganized phase. At this stage the ultrastructure of chloroplasts and mitochondria was considerably modified. The progressive changes of the parameters studied appeared to affect all of the cells in a given culture.

Journal Article↗

Stress and selective attention: the interplay of mood, cortisol levels, and emotional information processing.

The effects of a stressful challenge on the processing of emotional words were examined in college students. Stress induction was achieved using a competitive computer task, where the individual either repeatedly lost or won against a confederate. Mood, attention, and cortisol were recorded during the study. There were four findings: (1) Participants in the negative stressor condition were faster to shift attention away from negative words than positive or neutral words; (2) attentional shifts away from negative words were associated with stress-induced mood lowering; (3) participants in the negative stress condition with elevated scores on the Beck Depression Inventory were slow to disengage attention from all stimuli; and (4) elevated depression scores were associated with lower cortisol change from baseline during the experimental phase, and with higher cortisol levels during the recovery phase. These findings point to information-processing strategies as a means to regulate emotion, and to atypical features of cognitive and adrenocortical function that may serve as putative risk markers of depression.

Adolescent↗

Electromyogram, force and relaxation time during and after continuous electrical stimulation of human skeletal muscle in situ.

A technique for recording the surface electromyogram (e.m.g.) simultaneously with electrical stimulation of human skeletal muscle is described. During a fatiguing electrical stimulation the e.m.g. amplitude and force decreased in the same proportion. During recovery the e.m.g. was quickly normalized whereas force remained at a reduced level. Relaxation time increased during the stimulation and helps substantially in keeping up tension during a fatiguing contraction. In the recovery phase the rapid normalization of relaxation time counteracts recovery of tension. It is concluded that e.m.g. measurements alone can be misleading as an index of contraction force and that muscular fatigue during electrical stimulation can be attributed to excitation failure only to a lesser extent.

Adult↗

Characterization of anemia induced by avian osteopetrosis virus.

Chickens infected intravenously at 8 days after hatching with an avian osteopetrosis virus developed a severe, progressive anemia in the absence of osteopetrosis. The anemia was characterized as a pancytopenia, in which erythrocytes, granulocytes, and thrombocytes decreased concomitantly. Serum bilirubin levels were normal, whereas erythrocytes from infected chickens demonstrated a slightly elevated osmotic fragility. A negative Coombs test indicated that there was no evidence for erythrocyte-bound antibody. Erythrocytes from infected animals had slightly decreased 51Cr-labeled erythrocyte survival time when compared with normal. Examination of marrow histological preparations, together with ferrokinetic studies with 59Fe, indicated that marrow failure occurred during the acute phase of the anemia. Circulating virus was present during the development and acute phases of the anemia, but disappeared during the recovery phase of the disease. Neutralizing antibody appeared after the disappearance of circulating virus. It is concluded that virus infection induced both marrow failure (aplastic crisis) and decreased erythrocyte survival.

Alpharetrovirus↗

Immunoglobulin E response during measles.

Serum IgE levels were determined in 41 patients with measles infection. 23 patients (56%) had an increased level (greater than 20%) during the acute phase of the disease in comparison with the recovery phase. 14 showed no change, and decreased levels were observed in 4 patients only. In contrast, both IgG and IgA levels decreased or remained unchanged in the majority of the patients during disease activity. The changes in the pattern of serum immunoglobulins during measles might be attributed to selective depletion of T-cell subpopulations.

Adolescent↗

Developmental aspects of cerebrospinal fluid levels of beta-phenylethylamine and it's role in pediatric neurological disorders.

To clarify the role of beta-phenylethylamine (PEA) in pediatric neurological disorders, we have measured the cerebrospinal fluid (CSF) levels of PEA in 12 children with aseptic meningitis--6 were in the acute phase and the other 6 were in the recovery phase--and 5 children with Rett Syndrome (RS). The findings were compared with those obtained from 13 age-matched children with leukemia as child controls and from 10 adults patients without any neurological symptoms and signs as control. In the control group, the CSF PEA level was negatively correlated with age until 200 months (17 years) old. The mean PEA levels in meningitis and RS were significantly lower than that of child controls (p < 0.03). The alteration in the CSF levels of PEA may be related to transient changes in the dopaminergic tone in aseptic meningitis and neurological impairment, especially in the dopaminergic neurons in RS.

Age Factors↗

Effects of interleukin 3 and interleukin 6 on platelet recovery in mice treated with 5-fluorouracil.

We have studied the effects of murine recombinant interleukin 3 (IL-3) and human recombinant interleukin 6 (IL-6) on platelet recovery after administration of 5-fluorouracil (5-FU) to mice. 5-FU at 250 mg/kg body weight was administered as a single i.p. injection, and treatment with IL-3 alone, IL-6 alone, or a combination of IL-3 plus IL-6 was initiated immediately following the 5-FU or after a delay of 2 days. In addition, the effects of the combination of IL-3 plus IL-6 were evaluated following delays in initiation of their administration until 4 or 6 days after 5-FU treatment. In all schedules, the IL-3 and IL-6 treatments were discontinued 8 days following 5-FU. IL-3 and IL-6 were given s.c. three times daily; each injection of IL-3 was 80,000 U, each injection of IL-6 was 5000 U, and the combination comprised separate injections of IL-3 and IL-6 at the same respective doses. The combination of IL-3 and IL-6, initiated immediately or 2 days following 5-FU, diminished the platelet nadir and increased platelet counts on individual days during the recovery phase, thus apparently decreasing the time required for recovery to a normal platelet level. However, using self-modeling nonlinear regression, in order to analyze variability in the duration of thrombocytopenia, statistically significant shortening of the period of thrombocytopenia could not be consistently demonstrated. Neither IL-3 alone nor IL-6 alone had any effect on the above parameters. Recovery of hematocrit values and white blood cell levels was unaffected by administration of either IL-3 or IL-6 alone or the combination of both cytokines. We propose that IL-3 and IL-6 can act synergistically to enhance platelet recovery following 5-FU-mediated thrombocytopenia, but their modification of the response to 5-FU is modest.

Animals↗

[Serum myoglobin levels in patients with acute and chronic renal insufficiency].

The serum level of myoglobin was studied in 20 patients with acute renal failure, in 16 chronic renal failure patients and in 94 patients on maintenance haemodialysis. The serum myoglobin level was significantly increased in the oligoanuric phase of acute renal failure, rapidly decreased during diuretic phase and attained apparently normal values in the recovery phase. In patients with chronic renal failure the serum myoglobin level correlated with serum creatinine and creatinine clearance as a measure of the glomerular filtration rate, indicating a major role of kidney in the metabolism of this low-molecular weight protein. It was established that myoglobin could not be removed by dialysis membrane and analysis of the myoglobin level in endstage kidney disease patients on maintenance hemodialysis has shown an important extrarenal catabolism of this protein.

Acute Kidney Injury↗

Plasma alpha2-HS glycoprotein concentrations in patients with acute myocardial infarction quantified by a modified ELISA.

BACKGROUND: Human alpha2-HS glycoprotein (alpha2-HSG) is synthesized and secreted by the liver into circulation. Plasma concentrations of alpha2-HSG decrease significantly following infection, inflammation and malignancy. Since increased plasma concentrations of C-reactive protein are observed in patients with acute myocardial infarction (AMI), we hypothesized that plasma concentrations of alpha2-HSG would decrease during the initial phase of AMI and begin to increase in the recovery phase. METHODS: Twenty patients diagnosed with AMI were recruited for the study. A sensitive and specific ELISA was developed to assay alpha2-HSG concentrations in plasma. RESULTS: In AMI patients, plasma alpha2-HSG concentrations were decreased (281.3+/-25.8 mg/l, ranging from 132 to 489 mg/l on admission) compared to healthy individuals (312.3+/-9.9 mg/l, ranging from 210 to 450 mg/l) (P= 0.142). Interestingly, 40% of AMI patients demonstrated alpha2-HSG concentrations below 200 mg/l compared to none in the healthy control group. During the recovery period, alpha2-HSG concentrations begin to increase, with a mean+/-SEM of 290.1+/-22.1 mg/l. Regression analysis comparing plasma alpha2-HSG concentrations on admission to concentrations on discharge showed a significant positive correlation in matched-pair patient samples (P<0.01, r=0.45). CONCLUSIONS: We conclude that, in contrast to C-reactive protein, alpha2-HSG functions as a negative acute phase protein in AMI patients. Plasma alpha2-HSG concentrations start to decrease within a few hours after the onset of AMI and return to near normal concentrations during the recovery period (5-7 days after AMI).

Adult↗

Transiently raised intraocular pressure reveals pattern electroretinogram losses in ocular hypertension.

PURPOSE: It is known that the pattern electroretinogram (PERG) of normal subjects is reduced temporarily after short-term elevation of intraocular pressure (IOP). The authors evaluated PERG changes in ocular hypertension during and after transient IOP elevation. METHODS: Steady state (8 Hz) PERGs to sinusoidal gratings (1.7 cyc/deg spatial frequency) were recorded in seven untreated patients with ocular hypertension at medium risk (maximum IOP, 22 to 25 mm Hg; cup-disk ratio, 0.6 to 0.7; normal Humphrey 30-2 visual field results; positive family history), as well as in six age-matched normal subjects. Recordings were obtained for the baseline condition during a short-term (6-minute) IOP elevation (to 30 mm Hg) by using a suction cup apparatus and during a 6-minute recovery period after removal of the apparatus. RESULTS: During IOP elevation, PERG amplitudes were reduced significantly from baseline values in normal subjects and patients. However, PERG losses were significantly greater in patients (average loss from baseline after 4 minutes of IOP elevation: 72% +/- 7.6%) compared to controls (average loss after 2 minutes of IOP elevation: 40% +/- 7.5%). In the recovery phase, mean PERG amplitude returned to baseline values in normal subjects but not in patients, whose recovery took longer. In normal subjects, PERG phase did not change either during or after IOP elevation. In patients, however, PERG phase showed a delay from baseline during and after IOP elevation (average delay after 6 minutes of recovery: -41.1 degrees +/- 13 degrees). CONCLUSIONS: Results indicate that increasing IOP with scleral suction produces greater PERG losses in eyes with ocular hypertension than in normal eyes. This suggests that the inner retina of eyes with ocular hypertension may have a heightened sensitivity to vascular or mechanical changes induced by transient IOP elevation.

Adult↗

Relationship between average muscle fibre conduction velocity and EMG power spectra during isometric contraction, recovery and applied ischemia.

The relationship between muscle fibre conduction velocity (MFCV) and the power spectrum of surface EMGs in 3 human volunteers was studied during isometric contractions at 40% maximum voluntary contraction. In addition, the recovery of these two parameters was measured during short lasting contractions at the same force level every 30 s. The recovery phase was also studied during ischaemia, thereby preventing the recovery of MFCV. The mean MFCV was calculated by the cross-correlation method. The measurements were facilitated by a real-time estimation of the cross-correlation and the MFCV and by a graphic display of the digitised signal. During contraction a nearly linear relation was found between MFCV and the median frequency of the power spectrum (MPF). During recovery this relationship was lost in one subject: MPF restored much faster then MFCV. During recovery under ischemia MFCV did not recover, but MPF recovered partially in all subjects. It is concluded that the shift of the power spectrum to lower frequencies during fatigue cannot be explained by changes in MFCV alone. Central mechanisms also influence the power spectrum and studying the recovery of local muscle fatigue during ischemia may separate these influences from that of MFCV on the power spectrum during fatigue.

Adult↗

Romurtide, a synthetic muramyl dipeptide derivative, accelerates peripheral platelet recovery in nonhuman primate chemotherapy model.

We investigated the therapeutic effects of romurtide, a synthetic muramyl dipeptide derivative, on experimental thrombocytopenia induced by carboplatin in cynomolgus monkeys. A prolonged thrombocytopenia due to a severe myelosuppression was induced by carboplatin. Romurtide given subcutaneously elevated significantly the peripheral platelet counts during both early initiation and later recovery phase of thrombocytopenia, thereby shortening the time required for recovery to a normal platelet level and the duration of thrombocytopenia. An oral administration of romurtide was also found to have a similar therapeutic efficacy to subcutaneous administration. These results demonstrated a possible therapeutic potential of romurtide in the management of thrombocytopenia associated with myelosuppression.

Acetylmuramyl-Alanyl-Isoglutamine↗