The effect of growth hormone on the development of diabetic kidney disease in rats.

BACKGROUND: Nephropathy is the most severe complication of diabetes mellitus. We investigated the effect of exogenous growth hormone (GH) administration on renal function and matrix deposition in the streptozotocin (STZ) model of type I-diabetic rat. METHODS: Adult female STZ-diabetic rats (D), non-diabetic control rats injected with saline (C) and control and diabetic rats injected with bovine GH for 3 months (CGH and DGH, respectively) were used. RESULTS: The usual renal hypertrophy seen in D animals was more pronounced in the DGH group. Creatinine clearance increased only in the D rats, but not in the other groups, including DGH. Albuminuria was observed in the D animals but was significantly elevated in the DGH group. Glomeruli from DGH animals showed more extensive matrix accumulation (manifested as an increase in mesangial/glomerular area ratio). Renal extractable insulin-like growth factor (IGF-I) mRNA was decreased in the D and DGH groups, but renal IGF-I protein was not significantly increased. Renal IGF binding protein-1 was increased in the D groups and further increased in the DGH group, at both the mRNA and protein levels. CONCLUSIONS: GH-treated diabetic rats had less hyperfiltration and more albuminuria, concomitant with more glomerular matrix deposition, when compared with regular diabetic animals. This was associated with a significant increase in renal IGFBP-1, and dissociated from IGF-I changes. Thus, in this model, GH exacerbates the course of diabetic kidney disease.     

Direct and synaptic responses of the cat's medullary respiratory neurons evoked by microstimulation

The responses of single medullary neurons were evoked by microstimulation and recorded extracellularly in cats with spontaneous breathing under pentobarbital anaesthesia. Direct and synaptic responses were observed. In the silent phases of the respiratory neurons the latencies of direct responses were always longer (0.25–0.5 ms) than during the spontaneous discharge of these neurons (0.12–0.35 ms). Such phase-related variations of latency persist even when maximal currents are applied.The latencies of synaptic responses of expiratory and inspiratory neurons differed. The expiratory neurons gave two types of synaptic responses with a latency of about 0.8 ms (monosynaptic) or about 1.5 ms (probably disynaptic). The latencies of the evoked monosynaptic responses of the expiratory neurons varied from 0.6 to 1.2 ms depending on the phase of the respiratory cycle. The minimal latency of the synaptic responses of the inspiratory neurons under study was 1.2 ms. The typical latency varied between 1.75 and 2.8 ms. Some neurons had the late synaptic responses with a latency of about 5–9 ms. The synaptic responses of all the inspiratory neurons as well as the disynaptic responses of the expiratory neurons were evoked only during a spontaneous discharge which was followed by the inhibition of the spontaneous activity (lasting 20–100 ms).Thus it can be concluded that the excitatory pathways to expiratory neurons activated by microstimulation are mono- and disynaptic, whereas excitatory pathways to inspiratory neurons are polysynaptic.     

Effect of plant phenolic compounds on biofilm formation by Pseudomonas aeruginosa

In the natural environment, bacteria predominantly exist in matrix‐enclosed multicellular communities associated with various surfaces, referred to as biofilms. Bacteria in biofilms are extremely resistant to antibacterial agents thus causing serious problems for antimicrobial therapy. In this study, we showed that different plant phenolic compounds, at concentrations that did not or weakly suppressed bacterial growth, increased the capacity of Pseudomonas aeruginosa PAO1 to form biofilms. Biofilm formation of P. aeruginosa PAO1 was enhanced 3‐ to 7‐fold under the action of vanillin and epicatechin, and 2‐ to 2.5‐fold in the presence of 4‐hydroxybenzoic, gallic, cinnamic, sinapic, ferulic, and chlorogenic acids. At higher concentrations, these compounds displayed an inhibiting effect. Similar experiments carried out for comparison with Agrobacterium tumefaciens C58 showed the same pattern. Vanillin, 4‐hydroxybenzoic, and gallic acids at concentrations within the range of 40 to 400 μg/mL increased the production of N–3‐oxo‐dodecanoyl‐homoserine lactone in P. aeruginosa PAO1 which suggests a possible relationship between stimulation of biofilm formation and Las Quorum Sensing system of this bacterium. Using biosensors to detect N‐acyl‐homoserine lactones (AHL), we demonstrated that the plant phenolics studied did not mimic AHLs.     

Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.KEY WORDS: membrane transporters, molecular imaging, multidrug resistance, near infrared, optical imaging     

Targeting B cells and autoantibodies in the therapy of autoimmune diseases

B cells and B cell-derived autoantibodies play a central role in the pathogenesis of many autoimmune diseases. Thus, depletion of B cells via monoclonal antibodies such as Rituximab is an obvious therapeutic intervention and has been used successfully in many instances. More recently, novel therapeutic options targeting either the autoantibody itself or resetting the threshold for B cell activation have become available and show promising immunomodulatory and anti-inflammatory effects in a variety of animal models. The aim of this review is to summarize these results and to provide an insight into the underlying molecular and cellular pathways of these novel therapeutic interventions targeting autoantibodies and B cells and to discuss their value for human therapy.     

Detection of anomalous vertebral arteries by ultrasound as an alternative to radiological methods

In order to examine ‘ultrasound’ approach in detecting the course of the vertebral artery (VA) and its anomalies important for neck surgery. An observational study with retrospective analysis of ultrasound images. 500 VAs on 250 3D CT angiographies and 500 ultrasound images performed on the same set of patients were analyzed. The relationship between the extraosseous portions of the VA to the neck organs with a special emphasis to the thyroid gland area, and the abnormal position of the VA were detected. Ultrasound and CT 3D images were compared. Ultrasound detected that 29 out of 500 VAs were anomalous (5.8%), 3D CT detected 30 cases. These anomalies were found in 22 patients (8.8%) (23 for 3D CT; 9.2%), in 7 (31.8%) of them bilaterally. An abnormal level of entrance (C3, C4, and C5) was observed in all anomalous cases. An additional case detected by 3D CT indicated C7 level of entrance. The ultrasound data correspond the CT data in 96.7% of cases. In ten cases (33.3%) the anomalous VA run close to the thyroid gland even touching the lower pole (16.7%; n = 5) or the upper pole (10.0%; n = 3) of the gland. In ten cases (33.3%) the anomalous VA crossed common carotid artery and the internal jugular vein by a way of a median loop. The incidence of anatomic variations of the VA is significant. Preoperative ultrasound investigation allows precise identification of anomalous VAs. Radiation-free ultrasound investigation of blood vessels is as precise as CT 3D imaging.     

The correlation between aerobic fitness and motion sickness susceptibility

Susceptibility to motion sickness has been linked to aerobic fitness in several studies, however, these studies have not elucidated the underlying physiological mechanism by which increased aerobic fitness is related to a decreased ability to tolerate motion sickness stimuli. This pilot study provides further evidence of a relationship between aerobic fitness and motion sickness susceptibility. It also suggests that aerobic capacity is more specifically linked to signs and symptoms of vasomotor origin including stomach discomfort, nausea and/or vomiting, headache, and diaphoresis. By independently correlating vasomotor susceptibility and neurogenic susceptibility to maximum oxygen uptake, we find that vasomotor symptoms in particular are significantly increased in aerobically fit individuals. Larger studies should be conducted to confirm this relationship.     

Susceptibility to hepatitis A in patients with chronic liver disease due to hepatitis C virus infection: missed opportunities for vaccination

Hepatitis A virus (HAV) superinfection is associated with a high risk of liver failure and death in patients with underlying chronic liver disease. Although HAV vaccination is recommended for all patients with chronic hepatitis C virus (HCV) infection, little is known about adherence to these recommendations in clinical practice. The aims of this study were to determine the frequency of HAV testing and vaccination among patients with chronic HCV infection. We conducted a retrospective cohort study of 1,193 patients diagnosed with chronic HCV infection over a 1-year period. During 1,646 person-years of follow-up, patients were seen by their primary care provider a median of 10.0 times (interquartile range, 4.0-20.0). HAV antibody testing was performed in 640 subjects (53.6%), and 317 (49.5%) of those tested were susceptible (HAV antibody negative). Only 94 of the 1,193 patients (7.9%) received the HAV vaccine, including 26.8% of the 317 susceptible patients, 0.9% of the 323 patients who were already immune to HAV, and 1.1% of the 553 subjects who were never tested. Among the 94 vaccinated patients, 45 received only one dose of the vaccine. Three of the unvaccinated patients developed acute HAV infection during follow-up, and 1 of them died of acute liver failure. In conclusion, despite published recommendations to vaccinate against HAV in patients with chronic HCV infection, we found that HAV testing and vaccination rates were low in clinical practice. Public health programs to increase awareness about HAV vaccination in patients with chronic liver disease are needed.     

Sensorimotor recovery following spaceflight may be due to frequent square-wave saccadic intrusions

Square-wave jerks (SWJs) are small, involuntary saccades that disrupt steady fixation. We report the case of an astronaut (approximately 140 d on orbit) who showed frequent SWJs, especially postflight, but who showed no impairment of vision or decrement of postflight performance. These data support the view that SWJs do not impair vision because they are paired movements, consisting of a small saccade away from the fixation position followed, within 200 ms, by a corrective saccade that brings the eye back on target. Since many returning astronauts show a decrement of dynamic visual function during postflight locomotion, it seems possible that frequent SWJs improved this astronaut's visual function by providing postsaccadic enhancement of visual fixation, which aided postflight performance. Certainly, frequent SWJs did not impair performance in this astronaut, who had no other neurological disorder.