Serum adiponectin levels are significantly reduced during the second half of normal pregnancy.

PURPOSE: To demonstrate the physiologic changes in adiponectin levels during the first vs second half of pregnancy. METHODS: Sixty-six females with uncomplicated pregnancies and normal pre-gestational BMI had serum adiponectin levels obtained at various gestational ages. Thirty-one samples were obtained during the first half of their pregnancy vs 35 in the second half. Thirty-three healthy non-pregnant females with comparable ages and BMI were controls. RESULTS: Mean adiponectin levels were 9.55 microg/dl (95% CI 8.2-10.77) vs 9.48 microg/dl (95% CI 8.44-10.66) in the control group in the first half of pregnancy (p = NS). We noted a 21% reduction in mean adiponectin levels (7.51 microg/dl) during the second half of pregnancy (p = 0.03) compared to the first half of pregnancy. CONCLUSION: Early pregnancy does not affect adiponectin levels. However, there is a significant reduction in adiponectin levels during the second half of pregnancy.

Neither Cathodal nor Anodal Transcranial Direct Current Stimulation on the Left Dorsolateral Prefrontal Cortex alone or Applied During Moderate Aerobic Exercise Modulates Executive Function.

There is converging evidence that both aerobic exercise (AE) and transcranial direct current stimulation (tDCS) can acutely modulate executive functions (EF). In addition, recent studies have proposed the beneficial effects of applying tDCS during AE on physical performance. This study aimed to investigate whether tDCS applied during an AE session additionally or differently effects EF. Therefore, five experiments were conducted in a counterbalanced pre-post-retention crossover design to explore the acute effects of tDCS and AE on EF (inhibition and updating) once in isolation (i.e., either cathodal, anodal tDCS or AE alone as controls) and once in a combined application (i.e., anodal and cathodal tDCS during AE versus sham tDCS during AE). No differences were found in any experiment in the cognitive test parameters. However, in the case of anodal tDCS vs. sham during AE, heart rate was significantly affected. For cathodal tDCS vs. sham during AE, a significant Anova interaction indicated that cathodal tDCS during AE slightly reduced ratings of perceived exertion. The nonsignificant effects of tDCS on EFs are in contrast to previous studies, as no replication of existing observations could be achieved. Thus, the protocol applied in this study does not provide any strong evidence that a combination of AE and tDCS has any effects on EFs, but indicates effects on physiological parameters and subjective exhaustion ratings. Further research should consider changes in AE and tDCS parameters (e.g., intensity or exercise mode) and sequence of applications (online vs. offline).

A parametric fMRI investigation of context effects in sensorimotor timing and coordination.

Mounting evidence suggests that information derived from environmental and behavioral sources is represented and maintained in the brain in a context-dependent manner. Here we investigate whether activity patterns underlying movements paced according to an internal temporal representation depend on how that representation is acquired during a previous pacing phase. We further investigate the degree to which context dependence is modulated by different time delays between pacing and continuation. BOLD activity was recorded while subjects moved at a rate established during a pacing interval involving either synchronized or syncopated coordination. Either no-delay or a 3, 6 or 9s delay was introduced prior to continuation. Context-dependent regions were identified when differences in neural activity generated during pacing continued to be observed during continuation despite the intervening delay. This pattern was observed in pre-SMA, bilateral lateral premotor cortex, bilateral declive and left inferior semi lunar lobule. These regions were more active when continuation followed from syncopation than from synchronization regardless of the delay length putatively revealing a context-dependent neural representation of the temporal interval. Alternatively, task related regions in which coordination-dependent differences did not persist following the delay, included bilateral putamen and supplementary-motor-area. This network may support the differential timing demands of coordination. A classic prefrontal-parietal-temporal working memory network was active only during continuation possibly providing mnemonic support for actively maintaining temporal information during the variable delay. This work provides support for the hypothesis that some timing information is represented in a task-dependent manner across broad cortical and subcortical networks.

Repeated botulinum toxin injections can improve mobility in patients with spinal cord lesions.

AIM: The aim of this study was to increase the knowledge about the response to botulinum toxin (BTX) injections to spastic leg muscle motor points (MP) in spinal cord lesion (SCL) patients, and describe improvement of mobility with repeated BTX injections. METHODS: Six patients with ASIA grade C or D SCL were studied at the Loewenstein Rehabilitation Center, Israel. The main outcome measures were: modified Ashworth scale scores, range of motion (ROM), and mobility spinal cord independence measure (SCIM) scores. BTX was injected twice within a few weeks' interval to the MP of spastic leg muscles. The outcome measures were monitored before each injection and 2 weeks or more after the second injection. RESULTS: Following the first BTX injection the tonus decreased, ROM increased in all 6 patients, and mo- bility functioning improved in 4 of them. Following the repeated injection the tonus further decrea- sed, ROM further improved in 5 of 6 patients, and mobility functions further improved in 4 of 6 patients. CONCLUSION: BTX can improve mobility in patients with SCL. Repeated injections may enhance the effect despite the concern for resistance formation. Further research is needed to support the findings and determine the optimal BTX doses and intervals between injections.

Animal models and analytical approaches for understanding the relationships between wine and cancer.

We used two approaches for studying the relationships between wine consumption, wine composition and cancer In the first approach, a transgenic mouse model of human neurofibromatosis, combined with the use of well-defined, chemically purified diets, showed that red wine contains nonalcoholic components that can delay tumor onset. In additional studies, catechin, the main monomeric polyphenol of red wine, delayed tumor onset in this mouse model in a positive, linear relationship when incorporated into the diet at levels of 0.5-4 mmol/kg diet. In the second approach, low doses of the chemical carcinogen 2-amino-1-methyl-6-phenylimidazo(4, 5-b)pyridine (PhlP) were administered to rats, and formation of DNA adducts was evaluated by accelerator mass spectrometry. Consumption of red wine solids (the residue from red wine remaining after removal of alcohol and water) and the wine polyphenol quercetin did not influence PhlP-DNA adduct levels or induce liver enzymes (glutathione-S-transferase and quinone reductase). However, quercetin did alter distribution of PhlP in the rat tissues compared to control animals and animals fed other potential dietary chemopreventive agents, including phenylethyl isothiocyanate and sulforaphane. These studies demonstrate the feasibility of these approaches for studying the chemopreventive potential of dietary components at physiologic levels in

The delineation of an MMPI symptom pattern unique to lithium responders.

The author attempted to determine whether the Minnesota Multiphasic Personality Inventory (MMPI) would be sensitive to a symptom pattern unique to lithium-responsive patients regardless of diagnosis. Statistical analyses of the MMPI scores of lithium responders, lithium nonresponders, and a group of patients receiving other psychotropic drugs revealed that the depression, psychasthenia, mania, and social introversion scale scores significantly differentiated the lithium response and lithium nonresponse groups. No strong indications of significant difference were found between the MMPI scale scores of the lithium nonresponse and psychotropic groups. The results suggest that there is a lithium-responsive syndrome that exhibits a distinctive symptom pattern regardless of its varying phenomenological features in different individuals.

Antioxidant vitamin supplementation and lipid peroxidation in smokers.

Previous studies have shown that cigarette smoke enhances lipid peroxidation. This study examined the effect of daily consumption of a tomato-based juice supplemented with vitamin C (600 mg), vitamin E (400 IU, or 400 mg), and beta-carotene (30 mg) on various indexes of lipid peroxidation (breath pentane excretion and susceptibility of LDL to copper-mediated oxidation) in smokers. In addition, plasma lycopene and vitamin concentrations and total peroxyl radical trapping potential, a measure of antioxidant defenses, were assessed. Relative to the placebo juice, the vitamin-supplemented juice resulted in a significant decrease in breath-pentane excretion as well as a significant improvement in the resistance of LDL to oxidation. The lag phase of conjugated diene formation lengthened and the propagation rate decreased, indicating a decreased susceptibility of LDL to oxidative modification. Increased concentrations of plasma vitamin C, beta-carotene, and lycopene were found to be significantly correlated with the conjugated diene lag phase and rate of formation. Vitamin E was highly correlated with beta-carotene. Plasma total peroxyl radical trapping potential values did not change in response to supplementation. This study thus indicates that an antioxidant-supplemented drink can reduce lipid peroxidation and susceptibility of LDL to oxidation in smokers and may ameliorate the oxidative stress of cigarette smoke.

Activity testing of alveolar macrophages and changes in surfactant phospholipids after irradiation in bronchoalveolar lavage: experimental and clinical data.

This study presents results of bronchoalveolar lavage (BAL) after irradiation to the lungs in mice as well as clinical data. The number of BAL cells, mainly macrophages, lymphocytes, and granulocytes, changed in a time-dependent manner. The phagocytic activity of the macrophages measured as the phagocytosis of microbeads and measured as the esterase activity also showed a strong time-dependent increase during the acute phase up to 21 days after irradiation. The contents of surfactant phospholipids (SF) and sphingomyelin (SPH; as a parameter for cell death) were quantified by HPLC. Both were significantly changed between day 2 and 21 after irradiation. Three BALs of a patient with idiopathic interstitial pneumonitis, who had received an allogenic bone marrow graft after total body irradiation with 10 Gy, showed similar effects in the cellular and surfactant parameters. These data indicate that there are positive interactions between the number of different BAL cells, macrophage activity, and SF and SPH content in the preclinical model of the mouse as well as in the clinical situation after lung irradiation.

A convenient method for measuring receptor-cyclase coupling activity in whole blood: application to Duchenne muscular dystrophy.

Activity of the guanine nucleotide-binding regulatory (N protein) component of adenylate cyclase can be measured in extracts of whole blood, using a modification of an assay previously applied to erythrocyte membranes. N protein activities in the blood of three patients with Duchenne muscular dystrophy and eight heterozygous carriers of the disease did not differ significantly from activities measured in blood of seven normal subjects. In contrast, the modified assay showed a 50% deficiency of N protein activity in blood of four patients with pseudohypoparathyroidism, type I, in whom erythrocyte studies had previously demonstrated a comparable degree of N deficiency.

Effect of dantrolene sodium on spasticity associated with hemiplegia.

The effects of dantrolene sodium (Dantrium) were studied in 23 patients with hemiplegic spasticity, 13 of whom were younger than 50, and 10 older than 50. The dosage of dantrolene ranged from 100 mg per day initially to 600 mg per day maximally. The drug was most effective in reducing or abolishing clonus and somewhat less efficacious in decreasing the resistance to stretch and the tendon reflexes. Functionally, gait was improved and the patients found it easier to take care of their personal needs. In general, motor performance was improved. The observation that patients in the 50+ age group responded less well remains unexplained. Dantrolene sodium is a valuable tool in the management of spasticity due to hemiplegia.

The vascular architecture of human xenotransplanted tumors: histological, morphometrical, and ultrastructural studies.

This study was designed to examine the vascular system of human xenotransplanted tumors on nude mice with different complementary morphometrical and morphological methods. The vascular system shows a chaotic arrangement. There is an extreme heterogeneity in the vascular distribution and density. Large avascular regions could be identified in several non-necrotic tumors. There was no clear difference in the vascular density between the center and the periphery of the tumors, nor was there any zonal correlation for the distribution of the necrosis. With three-dimensional corrosion casts it could be demonstrated that clusters of vessels were directly beneath areas almost free of vessels. In the center, vessels often form a sinusoidal system with numerous blind ends without clearly discernible endothelial cells. Numerous irregular tumor-cell-lined sinusoids are visible next to endothelial-lined vessels with transmission electron microscopy. With scanning electron microscopy it could be demonstrated that large-calibre endotheliazed vessels were found in the direct vicinity or in the center of non-viable zones. Even large-calibre vessels have a capillary wall structure. Sometimes, a basement membrane cannot be observed at all or only incompletely. There are numerous indications of vascular discontinuities and leaks with a widespread intercellular occurrence of blood cells.

Radiation-induced changes in lung tissue and development of fibrosis determined by quantitative morphometric methods.

This study presents results of morphometric investigations of mouse lungs after single irradiation. An automatic image analyser was used to monitor pathological changes in morphological structure, especially the size and distribution of collagen fibres, the thickness of the septa and the diameters of alveoli in the lung. Radiation-induced changes in the area of alveoli and septa as well as collagen content were seen 11 weeks after irradiation. A dose-dependent increase in tissue and decrease in alveolar surface as well as a quantifiable increase in radiation oedema were seen. The septa were thickened and the total collagen content increased in a dose-dependent manner. The morphometric methods used here are suitable for determining changes in lung structure, particularly those in collagen content in the early phase of a pathological response after thorax or total body irradiation for conditioning in bone marrow transplantation.

Morphologic findings in bone marrow precursor cells in zinc-induced copper deficiency anemia.

Damage to the bone marrow elements, as shown by cytoplasmic vacuolization, has been reported in patients with acute alcohol intoxication, drug reactions, nutritional deficiencies, myeloproliferative syndromes, malignant hematologic conditions, some metabolic conditions, and in those treated with chemotherapeutic agents. A case of zinc toxicity with anemia, leukopenia, and cytoplasmic vacuolization of both myeloid and erythroid precursors is described. The patient described was a 30-year-old quadriplegic man who was receiving oral zinc to promote the healing of and prevention of decubitus ulcers. In the gut, dietary zinc interacts with copper in a competitive manner, and high levels of zinc can lead to copper deficiency. Zinc-induced copper deficiency anemia can be morphologically identified in the bone marrow preparations by cytoplasmic vacuolization of both myeloid and erythroid precursor elements.

Pharmacologic effects of A-49816, a new high-ceiling diuretic.

The pharmacologic effects of A-49816, a high-ceiling, loop diuretic, were evaluated in a single-blind, placebo-controlled, randomized trial. Eighteen (18) normal volunteers aged 19 to 40 years were divided into three groups. The subjects in each group received either placebo or three increasing doses of A-49816 with at least a one-week washout between doses. Nine doses of A-49816 (0.5 to 20 mg) were administered during the entire study. Urine volume and excretion of electrolytes were measured at timed intervals following dosing. A-49816 increased urine volume and excretion of sodium and chloride. Significant saluresis, chloruresis and diuresis were seen in most time periods following administration of the highest doses (12.5, 15 and 20 mg) of A-49816. Kaluresis was not consistently seen at any dose. The mean rates of urine output and sodium and chloride excretion were increased relative to placebo within 2 hours of drug administration. The mean rates of urine formation and sodium and chloride excretion peaked at 2-4 hours and often remained elevated at the 6-12 hour interval.

Mathematical model for adriamycin (doxorubicin) pharmacokinetics.

Adriamycin (doxorubicin), an active antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to protein and to tissue readily occurs. The drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of body weight and includes two peripheral adriamycin compartments and a subsystem for adriamycinol, a major metabolite. Plasma and urine concentrations of adriamycin and adriamycinol were determined for four patients treated with adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of adriamycinol immediately after IV infusion of adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of adriamycinol are the sum of adriamycinol concentrations and approximately 10% of the adriamycin concentrations. Corrected peak plasma concentrations of adriamycinol occur 2--12 h after infusion of adriamycin.

Practice-dependent modulation of neural activity during human sensorimotor coordination: a functional Magnetic Resonance Imaging study.

We investigated the degree to which differences in the pattern of blood oxygen level dependent activity (BOLD) between syncopated and synchronized coordination patterns are altered by practice. Baseline levels of BOLD activity were obtained from eight subjects while they syncopated or synchronized with an auditory metronome at 1.25 Hz. Subjects then practiced syncopation at the same rate for four consecutive sessions. Post practice scans of the two coordination patterns were then performed. Before practice, baseline syncopation activated a much broader network of both cortical and subcortical regions than synchronization that included Supplementary Motor Area (SMA), bilateral putamen, left thalamus, bilateral superior temporal gyrus as well as the vermis. This pattern of activity is hypothesized to reflect the extra timing and attention requirements of syncopation. After practice, activity in superior temporal gyrus and vermis were no longer observed during syncopation reflecting a reduction in the need for attention and the use of sensory feedback for guiding behavior. Surprisingly, post practice synchronization resulted in additional significant activations in SMA, inferior frontal gyrus and superior temporal gyrus as well as small activations in bilateral putamen. Practice with the more difficult syncopation task thus had a dual effect of decreasing the number of active regions during syncopation and increasing the number of active regions during synchronization. Since overt syncopation performance did not change significantly as a result of practice, these observed neural changes appear to be due to context- and history-dependent factors, rather than behavioral learning per se.

Biotech pharmaceuticals and biotherapy: an overview.

Broadly, the history of pharmaceutical biotechnology includes Alexander Fleming"s discovery of penicillin in a common mold, in 1928, and the subsequent development-prompted by World War II injuries-of large-scale manufacturing methods to grow the organism in tanks of broth. Pharmaceutical biotechnology has since changed enormously. Two breakthroughs of the late 1970s became the basis of the modern biotech industry: the interspecies transplantation of genetic material, and the fusion of tumor cells and certain leukocytes. The cells resulting from such fusion-hybridomas-replicate endlessly and can be geared to produce specific antibodies in bulk. Modern pharmaceutical biotechnology encompasses gene cloning and recombinant DNA technology. Gene cloning comprises isolating a DNA-molecule segment that corresponds to a single gene and synthesizing ("copying") the segment. Recombinant DNA technology, or gene splicing, comprises altering genetic material outside an organism-for example, by inserting into a DNA molecule a segment from a very different DNA molecule-and making the altered material (recombinant DNA) function in living things. Recombinant DNA technology enables modifying microorganisms, animals, and plants so that they yield medically useful substances, particularly scarce human proteins (by giving animals human genes, for example). This review, however, focuses not on pharmaceutical biotechnology"s methods but on its products, notably recombinant pharmaceuticals. It describes various types of biotech pharmaceuticals, their safety and effectiveness relative to the safety and effectiveness of conventionally produced pharmaceuticals, and the regulation of biotech pharmaceuticals.

Body composition in the elderly: the influence of nutritional factors and physical activity.

BACKGROUND: Controversy exists regarding the relative contribution of diet and exercise to body composition. Few studies have examined these associations in the elderly, where changes occur in the body fat to muscle ratio. OBJECTIVE: The primary objective of this paper is to determine whether energy intake or physical activity are associated with body composition. Secondly, to investigate whether specific macronutrients are associated with fat or lean tissue. DESIGN: Data (n= 1404) for this cross-sectional analysis were collected from a population-based sub-sample of elderly enrollees in the Cardiovascular Health Study (CHS). Dietary intake and physical activity were assessed by questionnaires. Body composition was measured by Dual Energy X-ray Absorptiometry (DEXA). Linear regression models were used to assess the associations of diet and activity with body composition. RESULTS: Total energy intake was not associated with any of the body composition measures. Higher dietary saturated fat was associated with higher percent body mass as fat and trunk fat in both sexes (p<0.01), and in men other dietary fats were associated with body fat. In women, distance walked was inversely associated with fat masses even after adjustment for pace of walking. In both sexes, faster pace of walking was associated with lower body and fat mass (p<0.01). Lean muscle mass was not associated with physical activity or dietary intakes. CONCLUSION: Physical activity and dietary fat intake in this the elderly population were more closely associated with body fat mass than was total energy intake.

NIR reflection measurements of hemoglobin and cytochrome aa3 in healthy tissue and tumors. Correlations to oxygen consumption: preclinical and clinical data.

OBJECTIVES: A new near infrared reflectance spectroscopy based technology (MULTISCAN OS 10/30) for non-invasive measurements of tissue oxygenation allows detection of absolute tissue hemoglobin concentration and saturation values in real time. METHODS: MULTISCAN OS 10/30 scans a tissue sector of defined geometry at 400 to 1200 nm wavelength with 0.3 nm intervals at a scan rate of up to 400 Hz in reflection mode. The newly developed algorithms are based on the entropy pattern of photons and allow the detection of absolute values of total hemoglobin (tHb), deoxy- (Hb) and oxy-hemoglobin (HbO2) in mg/ml tissue as well as tissue oxygen (saturation = tiSO2) in the range of 0 to 100% in real time. Cytochrome aa3 (Cyt) can be monitored simultaneously. RESULTS: Physiological Stimulation. Clamping experiments at the finger of volunteers, in the intestine of a pig, in the kidney of mice and rats showed a very fast, sensitive and tissue specific reaction. Changes in breathing and/or anesthesia conditions were immediately followed by corresponding changes of tissue oxygenation (brain, finger, skin). Simultaneous measurements of oxygen (HbO2), and cytochrome showed a strong correlation between both parameters. For validation purposes parallel polarographic measurements (pO2 measurements) were performed in mice. Furthermore angiographic data of patients as well as NMR/I data were compared with the NIR spectroscopy findings. Tumor Measurements. Patients with tumors of different origins showed significantly different oxygen values. The lowest level was found in glioblastoma (< 10% sat, < 1.0 mg/ml tHb), whereas renal carcinoma showed tremendously increased values (> 90% sat, > 5.0 mg/ml tHb). In contrast the surrounding healthy kidney tissue was significantly less oxygenated and perfused compared to the tumors. Oxygen Consumption Measurements. Oxygen consumption was measured in 16 patients after ligation of the blood supply (A. and V. renalis) to the kidney affected by tumor. All tumors showed a significantly lower consumption rate compared to the healthy tissue. These findings were controlled by animal experiments of human renal carcinomas on nude mice. The same results were obtained under these experimental conditions. CONCLUSION: MULTISCAN OS 10/30 is a new and useful tool for in vivo characterization of oxygen and cytochrome in healthy and tumor tissues. In many clinically relevant situations oxygen measurements can be helpful and support the clinical routine diagnostics.

Rehabilitating the older stroke patient: what's possible?

Eighty percent of survivors (approximately 140,000 per year) have a significant impairment of neurologic function, but are not totally disabled. These are the patients who may benefit from rehabilitation. Rehabilitation cannot restore the activity of paralyzed muscles, but it will train the patient to utilize remaining functions to compensate for what has been lost.