The effect of the training with the different combinations of frequency and peak-to-peak vibration displacement of whole-body vibration on the strength of knee flexors and extensors.

Whole-body vibration training has become a popular method used in sports and physiotherapy. The study aimed to evaluate the effect of different vibration frequency and peak-to-peak displacement combinations on men knee flexors and extensors strength in isokinetic conditions. The sample consisted of 49 male subjects randomly allocated to seven comparative groups, six of which exercised on a vibration platform with parameters set individually for the groups. The experimental groups were exposed to vibrations 3 times a week for 4 weeks. The pre- and post- isokinetic strength tests, with the angular velocities of 240°/s and 30°/s, were recorded prior to and 2 days after the training. After 4 weeks of whole-body vibration training, a significant increase was noted regarding the mean values of peak torque, average peak torque and total work for knee flexors at high angular velocity in Groups I (60 Hz/4 mm) and V (40 Hz/2 mm) (p<0.05). The mean percentage values of post-training changes to study parameters suggest that the training had the most beneficial effect in Groups I (60 Hz/4 mm) and IV (60 Hz/2 mm) (p<0.05). Whole-body vibrations during static exercise beneficially affected knee flexor strength profile in young men at high angular velocity. The combinations of 60 Hz/4 mm seem to have the most advantageous effects on muscle strength parameters.

Reduction of pressure ulcer size with high-voltage pulsed current and high-frequency ultrasound: a randomised trial.

OBJECTIVE: International guidelines recommend the use of ultrasound (US) and electrical stimulation (ES) for treating chronic and recurrent pressure ulcers (PUs). The methodology of these procedures, however, still needs elaboration and confirmation by clinical studies. This parallel-group, randomised, single-blind, prospective, controlled clinical trial was conducted to determine whether by using high-frequency ultrasound (HFUS) and high-voltage monophasic pulsed current (HVMPC), the rate of change in the area of older patients' PUs can be accelerated. METHOD: Patients were randomly assigned to receive either: standard wound care (SWC) involving supportive care and topical treatments; SWC+US (1MHz; 0.5 W/cm2; 20%; 1-3 minutes/cm2); or SWC+ES (HVMPC, 154 µs, 100 pps, 100 V, 250 µC/sec, 50 minutes/day). US and ES were administered once a day, 5 days a week. The primary outcome was change in PU surface area measured against baseline after 6 weeks of treatment with SWC, SWC+US, and SWC+ES. RESULTS: We recruited 77 patients, aged 60-95 years (80% aged over 70 years of age), with 88 Category II, III and IV PUs were enrolled in the study. The percentage reduction in the surface area of PUs at the end of treatment was significantly greater in the SWC+US group (mean ± standard deviation, 77.48±11.59 %; p=0.024) and the SWC+ES group (76.19±32.83%; p=0.030) versus the control group (48.97±53.42%). The SWC+ES group also had a significantly greater proportion of PUs that decreased in area by at least 50% or closed than the control group (p=0.05 and 0.031, respectively). The SWC+US and SWC+ES groups were not statistically significant different regarding treatment results. Clinical side effects were not recorded. CONCLUSION: The results show that HFUS and HVMPC are comparable regarding their effectiveness in reducing the size of PUs in older people. DECLARATION OF INTEREST: The authors have nothing to disclose. All research activities were funded by the Academy of Physical Education, Katowice, Poland.

Breathing biofeedback as an adjunct to exposure in cognitive behavioral therapy hastens the reduction of PTSD symptoms: a pilot study.

Although trauma-focused cognitive behavioral therapy (TF-CBT) with exposure is an effective treatment for posttraumatic stress disorder (PTSD), not all patients recover. Addition of breathing biofeedback to exposure in TF-CBT is suggested as a promising complementary technique to improve recovery of PTSD symptoms. Patients (n = 8) with chronic PTSD were randomized to regular TF-CBT or TF-CBT with complementary breathing biofeedback to exposure. PTSD symptoms were measured before, during and after TF-CBT with the Impact of Event Scale-Revised. The results show that breathing biofeedback is feasible and can easily be complemented to TF-CBT. Although PTSD symptoms significantly decreased from pre to post treatment in both conditions, there was a clear trend towards a significantly faster (p = .051) symptom reduction in biofeedback compared to regular TF-CBT. The most important limitation was the small sample size. The hastened clinical improvement in the biofeedback condition supports the idea that breathing biofeedback may be an effective complementary component to exposure in PTSD patients. The mechanism of action of breathing biofeedback may relate to competing working memory resources decreasing vividness and emotionality, similar to eye movement desensitization and reprocessing. Future research is needed to examine this.

Executive function in posttraumatic stress disorder (PTSD) and the influence of comorbid depression.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with neurocognitive deficits, such as impaired verbal memory and executive functioning. Less is known about executive function and the role of comorbid depression in PTSD. Recently, studies have shown that verbal memory impairments may be associated with comorbid depressive symptoms, but their role in executive function impairments is still unclear. OBJECTIVE: To examine several domains of executive functioning in PTSD and the potentially mediating role of comorbid depressive symptoms in the relationship between executive function and PTSD. METHOD: Executive functioning was assessed in 28 PTSD patients and 28 matched trauma-exposed controls. The Cambridge Neuropsychological Test Automated Battery (CANTAB) with subtests measuring response inhibition (SST), flexibility/set shifting (IED), planning/working memory (OTS) and spatial working memory (SWM) was administered in PTSD patients and trauma-exposed controls. Regression analyses were used to assess the predictive factor of PTSD symptoms (CAPS) and depressive symptoms (HADS-D) in relation to executive function when taking into account the type of trauma. Pearson's correlations were used to examine the association between PTSD symptom clusters (CAPS) and executive function. The mediating effects of depression and PTSD were assessed using regression coefficients and the Sobel's test for mediation. RESULTS: Our findings indicate that PTSD patients performed significantly worse on executive function than trauma-exposed controls in all domains assessed. PTSD symptoms contributed to executive functioning impairments (SST median correct, IED total errors, OTS latency to correct, SWM total errors and SWM strategy). Adding depressive symptoms to the model attenuated these effects. PTSD symptom clusters 'numbing' and to a lesser extent 'avoidance' were more frequently associated with worse executive function (i.e., IED total errors, OTS latency to correct and SWM total errors) than 'reexperiencing' and 'hyperarousal'. Depressive symptoms mediated the relation between PTSD and executive function on some executive function measures (IED total errors and OTS latency to correct), whereas PTSD did not mediate the relation between depression and executive function. CONCLUSIONS: PTSD patients perform worse on executive function. The impairments seem to be mostly associated with the less specific PTSD symptom cluster of 'numbing'. Depressive symptoms seem to mediate the relationship between PTSD and executive function. These findings may have clinical implications with regard to treatment indication and prognosis.

Anaerobic capacity of amateur mountain bikers during the first half of the competition season.

Sustained aerobic exercise not only affects the rate of force development but also decreases peak power development. The aim of this study was to investigate whether anaerobic power of amateur mountain bikers changes during the first half of the competition season. Eight trained cyclists (mean ± SE: age: 22.0 ±0.5 years; height: 174.6 ± 0.9 cm; weight: 70.7 ± 2.6 kg) were subjected to an ergocycle incremental exercise test and to the Wingate test on two occasions: before, and in the middle of the season. After the incremental exercise test the excess post-exercise oxygen consumption was measured during 5-min recovery. Blood lactate concentration was measured in the 4th min after the Wingate test. Maximum oxygen uptake increased from 60.0 ± 1.5 ml min(-1) kg(-1) at the beginning of the season to 65.2 ± 1.4 ml min(-1) kg(-1) (P < 0.05) in the season. Neither of the mechanical variables of the Wingate test nor excess post-exercise oxygen consumption values were significantly different in these two measurements. However, blood lactate concentration was significantly higher (P < 0.001) in season (11.0 ± 0.5 mM) than before the season (8.6 ± 0.4 mM). It is concluded that: 1) despite the increase of cyclists' maximum oxygen uptake during the competition season their anaerobic power did not change; 2) blood lactate concentration measured at the 4th min after the Wingate test does not properly reflect training-induced changes in energy metabolism.

In end stage osteoarthritis, cartilage tissue pentosidine levels are inversely related to parameters of cartilage damage.

OBJECTIVES: Age is the most prominent predisposition for development of osteoarthritis (OA). Age-related changes of articular cartilage are likely to play a role. Advanced glycation endproducts (AGEs) accumulate in cartilage matrix with increasing age and adversely affect the biomechanical properties of the cartilage matrix and influence chondrocyte activity. In clinical studies AGEing of cartilage and its relation to actual cartilage damage can only be measured by surrogate markers (e.g., serum, skin or urine AGE levels and imaging or biochemical markers of cartilage damage). In this study actual cartilage AGE levels were directly related to actual cartilage damage by use of cartilage obtained at joint replacement surgery. METHODS: Cartilage and urine samples were obtained from 69 patients undergoing total knee replacement. Samples were analyzed for pentosidine as marker of AGE. Cartilage damage was evaluated macroscopically, histologically, and biochemically. RESULTS: Cartilage and urine pentosidine both increased with increasing age. The higher the macroscopic, histological, and biochemical cartilage damage the lower the cartilage pentosidine levels were. In multiple regression analysis age is not found to be a confounder. CONCLUSION: There is an inverse relation between cartilage AGEs and actual cartilage damage in end-stage OA. This is likely due to ongoing (ineffective) increased turnover of cartilage matrix proteins even in end stage disease.

Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage.

OBJECTIVE: Adipose tissue is an endocrine tissue releasing adipokines suggested to be involved in the pathogenesis of osteoarthritis (OA). Nevertheless, their relative contribution and exact mechanisms are still ambiguous. The aim of this study is to compare serum adipokine levels between end-stage knee OA patients and controls and to relate these serum levels to local parameters of cartilage damage and synovial inflammation. METHODS: Serum was collected from 172 severe knee OA patients, shortly before total knee replacement (TKR) surgery and from 132 controls without radiographic knee OA [Kellgren & Lawrence (K&L) = 0]. Serum adiponectin, leptin, and resistin levels were measured by enzyme-linked immunosorbent assay (ELISA). Cartilage and synovial tissue were collected at TKR surgery and assessed for cartilage degeneration and synovial inflammation by histochemistry and biochemical analyses. RESULTS: The adipokine levels were all distinctly higher in OA patients as compared to controls. Especially adiponectin and leptin were associated with female gender (stand beta = 0.239 and 0.467, respectively, P < 0.001) and body mass index (BMI) (stand beta = -0.189 and 0.396, respectively, P < 0.001). No associations between serum levels of adipokines and cartilage damage (histochemistry, proteoglycan content) were found whereas weak but positive associations with synovial inflammation were found [adiponectin and interleukin-1ß (IL-1ß), stand beta = 0.172, P = 0.02; resistin and histology, stand beta = 0.183, P = 0.034, adjusted for demographics]. CONCLUSION: This study suggests an important involvement of adipokines in OA patients considering their high serum levels compared to controls. Associations of systemic adipokines with local synovial tissue inflammation were found, although not represented by similar relations with cartilage damage, suggesting that adipokines are of relevance in the inflammatory component of OA.

Compulsive carnival song whistling following cardiac arrest: a case study.

BACKGROUND: Compulsivity is the repetitive, irresistible urge to perform a behavior, the experience of loss of voluntary control over this intense urge and the tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is part of obsessive-compulsive disorder (OCD), but may occasionally occur as stand-alone symptom following brain damage induced by cardiac arrest. In this case report, we describe a patient who developed compulsivity following cardiac arrest. We review diagnostic options, underlying mechanisms and possible treatments. CASE PRESENTATION: A 65-year-old man presented at our clinic with continuous compulsive whistling following cardiac arrest. Neither obsessive-compulsive symptoms, nor other psychiatric complaints were present prior to the hypoxic incident. An EEG showed diffuse hypofunction, mainly in baso-temporal areas. Treatment with clomipramine resulted in a decrease of whistling. DISCUSSION: This case report illustrates de novo manifestation of compulsivity following cardiac arrest and subsequent brain damage and gives additional information on diagnostic options, mechanisms and treatment options. Differential diagnosis between stereotypies, punding, or OCD is difficult. Compulsivity following brain damage may benefit from treatment with serotonin reuptake inhibitors. This finding enhances our knowledge of treatments in similar cases.

Comparison of the effectiveness of trauma-focused cognitive behavioral therapy and paroxetine treatment in PTSD patients: design of a randomized controlled trial.

BACKGROUND: The two most common interventions for Posttraumatic Stress Disorder (PTSD) are pharmacological treatment with SSRIs such as paroxetine and psychological treatment such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). International guidelines recommend trauma-focused psychological interventions for all PTSD patients as first-line treatment (NICE). However, no clear-cut evidence is available to support this recommendation. METHODS/DESIGN: In order to compare pharmacological treatment (paroxetine) and psychological treatment (TF-CBT) in (cost-) effectiveness on the short and the long term, we will randomize 90 patients with chronic PTSD to either paroxetine (24 weeks) or TF-CBT (10-12 weeks). We will assess symptom severity and costs before and after the intervention with the Clinician Administered PTSD Scale (CAPS), the Clinical Global Impression Scale (CGI) and the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P). DISCUSSION: This study is unique for its direct comparison of the most commonly used psychological intervention (TF-CBT) and pharmacological intervention (paroxetine) on (cost-) effectiveness on the short and the long term. The anticipated results will provide relevant evidence concerning long-term effects and relapse rates and will be beneficial in reducing societal costs. It may also provide information on who may benefit most from which type of intervention. Some methodological issues will be discussed. TRIAL REGISTRATION: Dutch Trial registration: NTR2235.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review.

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

Lack of association between aspirin-triggered 15-hydroxyeicosatetraenoic acid release and mast cell/eosinophil activation in nasal polyps from aspirin-sensitive patients.

BACKGROUND: The mechanism of aspirin sensitivity in patients with asthma and rhinosinusitis has been attributed to arachidonic acid metabolism abnormalities. OBJECTIVE: We aimed to test whether aspirin-triggered generation of 15-hydroxyeicosatetraenoic acid (15-HETE) in nasal polyp dispersed cells (NPDCs) from aspirin-sensitive patients is associated with activation of inflammatory cells. METHODS: Polyps were obtained from 11 aspirin-sensitive and 19 aspirin-tolerant patients with chronic rhinosinusitis. NPDCs were stimulated by aspirin or calcium ionophore. Levels of 15-HETE, leukotriene (LT) C4, eosinophil cationic protein (ECP), and tryptase were measured in NPDC supernatant. RESULTS: NPDCs from aspirin-sensitive patients contained more eosinophils (14% vs 9%, P < .05) and released 2.4-fold more ECP (P < .01) at baseline. Stimulation with aspirin (200 microM) resulted in a significant increase in 15-HETE generation only in tissue from aspirin-sensitive patients (mean increase, 82%) but did not induce any increase in the release of LTC4, ECP, or tryptase. Preincubation with calcium ionophore resulted in significantly enhanced generation of 15-HETE, ECP, tryptase, and LTC4 in patients from both groups. Incubation of NPDCs with misoprostol inhibited aspirin-induced 15-HETE generation in aspirin-sensitive patients and calcium ionophore-induced 15-HETE, ECP, and tryptase release in both aspirin-sensitive and aspirin-tolerant patients. CONCLUSION: Our study demonstrated that aspirin-induced 15-HETE generation in nasal polyps from aspirin-sensitive patients is not associated with activation of mast cells and eosinophils. Misoprostol has a potent inhibitory effect on the activation of cells derived from the site of nasal mucosal inflammation, regardless of sensitivity to aspirin.

T cell inflammatory response, Foxp3 and TNFRS18-L regulation of peripheral blood mononuclear cells from patients with nasal polyps-asthma after staphylococcal superantigen stimulation.

BACKGROUND: Staphylococcal superantigens may modulate airway inflammatory disease. OBJECTIVE: We assessed the effect of Staphylococcus aureus enterotoxin B (SEB) on T cell activation in patients with nasal polyps and asthma, and its possible link to aspirin hypersensitivity. METHODS: Leucocytes were isolated from five healthy subjects (controls), five asthmatics with nasal polyps without (NP-ATA) and five with aspirin-induced asthma (NP-AIA). Cells were incubated with increasing concentrations of SEB for 4 and 18 h. Release of T(H)1/T(H)2 cytokines was assessed by Cytometric Bead-Array. Foxp3 and TNFRS18-L expression were analysed by qPCR and flow cytometry. RESULTS: After 4 and 18 h, SEB significantly increased IFN-gamma, IL-4, TNF-alpha, IL-5 and IL-2 concentrations in supernatants of both NP polyp groups compared with controls. Baseline Foxp3 was significantly decreased in both NP-asthma groups. Incubation with SEB for 4 h induced a limited up-regulation of Foxp3 in NP-AIA patients, which was switched off consecutively. Foxp3 was significantly up-regulated in the control group after 18 h, but not in the NP-asthmatic groups. In parallel, TNFRS18-L mRNA significantly increased after 18 h in the NP-asthma groups compared with control subjects. This molecule was highly expressed in CD11c(+)CD14(+) cells and its levels increased after 18 and 24 h culture in the NP-asthma patients. CONCLUSION: SEB induces both T(H)1 and T(H)2 pro-inflammatory responses in patients with nasal polyps and asthma regardless of the presence of aspirin hypersensitivity. The nature of this response may be linked to a basal deficiency of Foxp3 observed in the NP-asthmatic patients and/or to the up-regulation of TNFRS18-L on monocytes/dendritic cell precursors.

The chondroprotective effect of selective COX-2 inhibition in osteoarthritis: ex vivo evaluation of human cartilage tissue after in vivo treatment.

OBJECTIVE: Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo. METHODS: Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo. RESULTS: When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased. CONCLUSION: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.

Involvement of 15-lipoxygenase and prostaglandin EP receptors in aspirin-triggered 15-hydroxyeicosatetraenoic acid generation in aspirin-sensitive asthmatics.

BACKGROUND: The mechanism of aspirin (acetylsalicylic acid: ASA) hypersensitivity in asthmatic patients is related to arachidonic acid metabolism abnormalities, and specific triggering by ASA of 15-hydroxyeicosatetraenoic acid (15-HETE) generation was observed in leucocytes from aspirin-sensitive (AS) but not from aspirin-tolerant (AT) asthmatics. OBJECTIVE: The aim of this study was to identify the enzymatic pathway involved in ASA-induced 15-HETE generation in AS asthmatics and to assess the regulatory role of prostaglandin EP receptors. METHODS: Peripheral blood leucocytes (PBLs) were isolated from AS (n=18) and AT (n=20) asthmatics and challenged with ASA, with and without pre-incubation with caffeic acid (CA) [15-lipoxygenase (15-LO) inhibitor] or prostaglandin receptor non-specific (misoprostol, sulprostone) and specific EP1-4 receptors agonists. Eicosanoids were measured in supernatants using specific immunoassays. RESULTS: Aspirin triggered 15-HETE generation in PBLs of AS asthmatics (mean increase 292%) but not in AT asthmatics and inhibited prostaglandin(2) (PGE(2)) generation in both groups of patients to the same degree. Leucocytes from AS patients produced less PGE(2), both before and after ASA incubation. Pre-incubation of PBLs with CA decreased basal 15-HETE production in all patients and completely inhibited ASA-induced 15-HETE generation in AS asthmatics. CA did not change basal PGE(2) production but enhanced induced by ASA inhibition of PGE(2). Non-specific agonists of EP receptors (misoprostol and sulprostone) did not affect basal 15-HETE production but inhibited in a dose-dependent manner the ASA-induced increase of 15-HETE generation in AS asthmatics. On the contrary, in AT asthmatics, pre-incubation of PBLs with misoprostol or sulprostone resulted in a significant increase in 15-HETE generation after addition of ASA (200 microm). EP1-3 receptor agonists inhibited (range 72-94%) the ASA-induced 15-HETE production significantly. CONCLUSION: Our study demonstrated that ASA-triggered 15-HETE generation involves the activation of 15-LO and is modulated by prostaglandin EP1-3 receptors. The relevance of these observations to the mechanism of in vivo ASA-induced asthmatic attack remains to be established.

Favorable resolution of hepatic infarctions in transplanted liver after portal vein thrombosis treated by surgical thrombectomy: a case report.

Portal vein thrombosis (PVT) after orthotopic liver transplantation (OLT) is a life-threatening complication associated with a high rate of graft loss and patient death, with reported incidence of 1% to 2% in adults. We report a case of an early PVT after OLT complicated by hepatic infarctions in the liver graft. After surgical thrombectomy and restoration of the portal inflow, hepatic infarctions resolved spontaneously within 6 months, which was confirmed by computed tomography.

FOXO1 is a TXN- and p300-dependent sensor and effector of oxidative stress in diffuse large B-cell lymphomas characterized by increased oxidative metabolism.

Molecular profiling has led to identification of subtypes of diffuse large B-cell lymphomas (DLBCLs) differing in terms of oncogenic signaling and metabolic programs. The OxPhos-DLBCL subtype is characterized by enhanced mitochondrial oxidative phosphorylation. As increased oxidative metabolism leads to overproduction of potentially toxic reactive oxygen species (ROS), we sought to identify mechanisms responsible for adaptation of OxPhos cells to these conditions. Herein, we describe a mechanism involving the FOXO1-TXN-p300 redox-dependent circuit protecting OxPhos-DLBCL cells from ROS toxicity. We identify a BCL6-dependent transcriptional mechanism leading to relative TXN overexpression in OxPhos cells. We found that OxPhos cells lacking TXN were uniformly more sensitive to ROS and doxorubicin than control cells. Consistent with this, the overall survival of patients with high TXN mRNA expression, treated with doxorubicin-containing regimens, is significantly shorter than of those with low TXN mRNA expression. TXN overexpression curtails p300-mediated FOXO1 acetylation and its nuclear translocation in response to oxidative stress, thus attenuating FOXO1 transcriptional activity toward genes involved in apoptosis and cell cycle inhibition. We also demonstrate that FOXO1 knockdown in cells with silenced TXN expression markedly reduces ROS-induced apoptosis, indicating that FOXO1 is the major sensor and effector of oxidative stress in OxPhos-DLBCLs. These data highlight dynamic, context-dependent modulation of FOXO1 tumor-suppressor functions via acetylation and reveal potentially targetable vulnerabilities in these DLBCLs.

Pituitary follistatin regulates activin-mediated production of follicle-stimulating hormone during the rat estrous cycle.

Follistatin, an activin-binding protein, plays a key role in the modulation of activin-dependent functions. In the anterior pituitary, activin stimulates the synthesis and secretion of FSH. In the current study, we assessed the roles of locally produced activin and follistatin in the control of FSH gene expression and secretion. The anterior pituitary gland follistatin content was measured at frequent intervals during the rat estrous cycle. Follistatin protein levels were high before the primary gonadotropin surges, decreased by 50% on proestrous evening, and rebounded to a peak at midnight on proestrus before returning to presurge levels on estrus morning. Changes in pituitary follistatin protein content were preceded by parallel changes in pituitary follistatin messenger RNA (mRNA). The trough in follistatin protein content on proestrus coincided with a peak in circulating levels of free activin A (not bound to follistatin) and a sharp rise in FSHbeta mRNA levels, suggesting that decreased pituitary follistatin leads to increased available activin. To quantitate the contribution of pituitary free activin to pituitary expression of FSHbeta mRNA and the primary and secondary serum FSH surges, rats were infused through carotid catheters with saline or recombinant human follistatin (288-amino acid isoform; rhFS-288) at different times during the estrous cycle. Infusion of rhFS-288 on diestrus did not affect FSH production. In contrast, infusion of rhFS-288 during the secondary FSH surge decreased the peaks in FSHbeta mRNA and serum FSH by 63% and 47%, respectively, relative to those in saline-infused control animals. Infusion of rhFS-288 during the primary FSH surge decreased serum FSH to a lesser degree (24%). These data indicate a physiological role for pituitary follistatin in the control of activin-mediated FSH synthesis and secretion during the rat estrous cycle.

Assessment of new radioimmunoassay kit for determining urinary albumin at low concentrations: comparison with radial immunodiffusion.

The assay characteristics of a new radioimmunoassay kit for determining urinary albumin at low concentrations were studied. The sensitivity for urinary albumin was 2 mg/l, the analytical range 2 to 40 mg/l, and interassay coefficient of variation less than 12%. In a method comparison study entailing diabetic urine samples covering an albumin concentration of 2 to 150 mg/l the kit compared adequately with radial immunodiffusion (mean difference between methods = 2 mg/l; residual standard deviation = 4.6 mg/l), absolute variation between methods increasing with the concentration. The kit required much less skill than radial immunodiffusion but its capital and running cost were higher.

The effect of 5-fluorocytosine on the blastospores and hyphae of Candida albicans.

In Candida albicans the continued increase in dry weight, in cell volume and in hyphal length during 5FC treatment is mainly due to increased amount of carbohydrate despite the decreased amounts of nucleic acids. Incorporation studies with 32PO4 (for RNA) in C. albicans and with 3H-thymidine-monophosphate (for DNA) in a thymidine-utilising strain of Saccharomyces cerevisiae have shown that the decreased amounts of nucleic acids were due to an inhibition of synthesis of RNA and DNA by 5FC. Nuclear-staining techniques on the hyphal phase of C. albicans showed that 5FC inhibits nuclear division. The changes in amounts of protein during 5FC treatment do not wholly explain the changes in cell size although 14C-histidine incorporation experiments showed that protein synthesis continued in the presence of 5FC. 14C-glucose incorporation in the presence of 5FC showed an initial accelerated synthesis of carbohydrate with a maintained level of synthesis after 16 h. This abnormal pattern of synthesis correlates with the increase in amount of carbohydrate and in cell size and hyphal elongation. 5FC inhibits DNA synthesis, and all manifestations of unbalanced growth that culminate in the cell volume changes appear to be a consequence of that inhibition.

Urinary albumin excretion in healthy adult subjects: reference values and some factors affecting their interpretation.

A conventional radioimmunoassay has been used to measure urinary albumin concentration in overnight, recumbent and daytime, ambulant samples from 127 healthy, normotensive volunteers (mean age 33.3 yr SD 12.4; 59 males, 68 females). Reference values were obtained for urine albumin concentration (mg/l), albumin/creatinine ratio (mg/mmol), and albumin excretion rate (microgram/min). The frequency distributions of these variables were positively skewed, but became Gaussian on logarithmic transformation of the data. Albumin excretion was significantly higher in daytime, ambulant samples than in overnight, recumbent samples (p less than 0.001). Surface area was not correlated with urine albumin concentration but it was negatively correlated with urine albumin/creatinine ratio (p less than 0.05) due to the association between surface area and creatinine excretion. Urine albumin concentration was negatively correlated with age, but this was due to a higher urine flow rate in older subjects. There was no significant association with sex or with mean arterial blood pressure in the normal range. Two repeated measurements showed that variability was high and comparable for urine albumin concentration, albumin/creatinine ratio and albumin excretion rate: it was not significantly less in overnight, recumbent than in day-time, ambulant samples.