Fluoxetine attenuates the effects of pentylenetetrazol on rat freezing behavior and c-Fos expression in the dorsomedial periaqueductal gray

The aim of the study was to investigate the role of the periaqueductal gray (PAG) in anxiolytic-like actions of fluoxetine in animals treated with an anxiogenic drug, pentylenetetrazol (PTZ), and subjected to fear conditioning procedure. The data showed that PTZ given at the dose of 30 mg/kg 15 min before a retention trial significantly decreased freezing reaction (p<0.01), and potently enhanced rat locomotor activity (p<0.01), in comparison to the control group. These effects were reversed by prior (60 min) administration of fluoxetine (20 mg/kg). Simultaneously, PTZ significantly increased c-Fos expression in the dorsomedial periaqueductal gray (DMPAG), examined 2h after the retention trial, in comparison to the control group (p<0.01). Fluoxetine (20 mg/kg) administered 60 min before PTZ reversed this effect. PTZ given at the same dose and time interval in the open field test did not affect rat locomotor behavior. Importantly, fluoxetine pretreatment did not change PTZ concentration in brain tissue. Our experiment based on PTZ-enhanced aversive conditioning revealed that acutely administered fluoxetine antagonized PTZ-induced panic-like behavior, and this phenomenon was accompanied by inhibition of activity of DMPAG.     

Ozonotherapy in an Induced Septic Shock. I. Effect of Ozonotherapy on Rat Organs in Evaluation of Free Radical Reactions and Selected Enzymatic Systems

The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in rats with an induced septic shock. The studies were conducted on adult male rats of Wistar strain. Four groups of the animals, each of 15 rats, included: I—control group, (C); II—animals intraperitoneally administered with O₂/O₃ (CO), III—rats given of Escherichia coli endotoxin (lipopolysaccharide—LPS) (CL), IV—rats administered with the lipopolysaccharide plus administered with the oxygen/ozone mixture (OL). Activities of catalase and superoxide dismutase and of free radical reactions were estimated. The exposure to LPS augmented activities of SOD and of catalase in liver, lungs and heart. In all the examined organs LPS induced significant changes in levels of free radicals. Except of the lungs, parallel administration of the rats with LPS and ozone/oxygen revoked development of the alterations. The obtained results point to a strong, stabilizing and regenerative effect of ozonotherapy.     

Accelerated senescence of human peritoneal mesothelial cells exposed to high glucose: the role of TGF-beta1

Cellular senescence can be activated in response to noxious environmental stimuli. A senescent-like phenotype has been detected in the peritoneal mesothelium of mice exposed to high intraperitoneal glucose. We have sought to examine whether high glucose (HG) can induce the senescence program in human peritoneal mesothelial cells (HPMC) in vitro. Senescence of omentum-derived HPMC was induced by serial passages. Cells were cultured in media containing either 5 mM glucose, 30 mM glucose, or 5 mM glucose and 25 mM mannitol (M) for osmotic control. Compared with HPMC cultured in low glucose, the growth rate of cells exposed to HG was significantly decreased so that the cells reached fewer population doublings before entering senescence. Exposure to HG led to increased expression of senescence-associated beta-galactosidase (SA-beta-Gal) and of the cell cycle inhibitors p21(Waf1) and p27(Kip1). Late-passage HPMC exposed to HG displayed marked hypertrophy and released increased amounts of fibronectin and TGF-beta1. These effects were absent from HPMC treated with equimolar M. Exposure of early-passage HPMC to exogenous recombinant TGF-beta1 induced a senescence marker SA-beta-Gal in a dose-dependent manner and mimicked other senescence-associated alterations induced by HG. The addition of anti-TGF-beta1 neutralizing antibody partially reduced the activation of HG-induced SA-beta-Gal. These results indicate that chronic exposure to elevated glucose may result in TGF-beta1-mediated accelerated senescence of HPMC in vitro, which may hypothetically contribute to the peritoneal membrane dysfunction during peritoneal dialysis in vivo.     

The Accuracy of Prevalent Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches

Due to concerns about cumulative radiation exposure in the pediatric population, it is not standard practice to perform spine radiographs in most conditions that predispose to vertebral fracture (VF). In this study we examined the accuracy of two clinical predictors, back pain and lumbar spine bone mineral density (LS BMD), to derive four case-finding paradigms for detection of prevalent VF (PVF). Subjects were 400 children at risk for PVF (leukemia 186, rheumatic disorders 135, nephrotic syndrome 79). Back pain was assessed by patient report, LS BMD was measured by dual-energy X-ray absorptiometry, and PVF were quantified on spine radiographs using the modified Genant semiquantitative method. Forty-four patients (11.0%) had PVF. Logistic regression analysis between LS BMD and PVF produced an odds ratio (OR) of 1.9 (95% confidence interval [CI], 1.5 to 2.5) per reduction in Z-score unit, an area under the receiver operating characteristic curve of 0.70 (95% CI, 0.60 to 0.79), and an optimal BMD Z-score cutoff of −1.6. Case identification using either low BMD alone (Z-score < −1.6) or back pain alone gave similar results for sensitivity (55%, 52%, respectively), specificity (78%, 81%, respectively), positive predictive value (PPV; 24%, 25%, respectively), and negative predictive value (NPV; 93%, 93%, respectively). The paradigm using low BMD plus back pain produced lower sensitivity (32%), higher specificity (96%), higher PPV (47%), and similar NPV (92%). The approach using low BMD or back pain had the highest sensitivity (75%), lowest specificity (64%), lowest PPV (20%), and highest NPV (95%). All paradigms had increased sensitivities for higher fracture grades. Our results show that BMD and back pain history can be used to identify children with the highest risk of PVF so that radiography can be used judiciously. The specific paradigm to be applied will depend on the expected PVF rate and the clinical approach to the use of radiography. © 2019 American Society for Bone and Mineral Research.     

Ten-year follow-up after combined coronary artery bypass grafting and transmyocardial laser revascularization in patients with disseminated coronary atherosclerosis

Coronary artery disease involving heavily calcified lesions has been associated with worse short- and long-term outcomes including increased mortality. This paper aims to evaluate long-term survival benefit when CABG + transmyocardial laser revascularization (TMLR) are performed on the hearts of patients with disseminated coronary atherosclerosis (DCA). This novel retrospective study was conducted between 1997 and 2002 and followed 86 patients with ischemic heart disease and severe DCA who underwent TMLR using a Holmium:YAG laser and/or CABG. There were 46 patients who had CABG plus TMLR on at least one heart wall (“combined therapy group”) and 40 patients who had CABG or TMLR separately on at least one heart wall (“single therapy group”). For the whole group, actuarial survival at 10 years was 78.3% in the combined group compared to 72.5% in the single therapy group (p?=?0.535). Ten-year survival in the combined vs. single therapy group for the anterior heart walls was 100 vs. 72.2% (p?=?0.027). For the lateral and posterior heart walls were 73.7 vs. 73.3% (p?=?0.97) and 84.2 vs. 72% (p?=?0.27), respectively. Kaplan-Meier survival analysis showed benefit only for the anterior heart wall (F Cox test, p?=?0.103). Single therapy procedures on all heart walls (odds ratio 1.736, p?=?0.264) or on the anterior heart wall only (odds ratio 3.286, p?=?0.279) were found to be predictors of 10-year late mortality. Combined therapy (TMLR + CABG) provides benefit for perioperative mortality and long-term survival only when provided on the anterior heart wall. For patients with disseminated coronary atherosclerosis, cardiac mortality was found to be increased when followed up 6 years later, regardless of the therapy applied.     

A rehabilitation tool for functional balance using altered gravity and virtual reality

Background  

There is a need for effective and early functional rehabilitation of patients with gait and balance problems including those with spinal cord injury, neurological diseases and recovering from hip fractures, a common consequence of falls especially in the elderly population. Gait training in these patients using partial body weight support (BWS) on a treadmill, a technique that involves unloading the subject through a harness, improves walking better than training with full weight bearing. One problem with this technique not commonly acknowledged is that the harness provides external support that essentially eliminates associated postural adjustments (APAs) required for independent gait. We have developed a device to address this issue and conducted a training study for proof of concept of efficacy.     

Improvement in the laboratory recognition of lyme borreliosis with the combination of culture and PCR methods.

BACKGROUND: Lyme disease is a multisystem, multistage infection caused by three genospecies of the Borrelia burgdorferi sensu lato species. The diagnosis of Lyme disease is based on a history of tick-bite, physical examination, and serological tests. In the seronegative patients with Lyme borreliosis symptoms, additional testing should be introduced. METHODS: The study group was composed of 240 hospitalized patients presented with various clinical symptoms suggesting Lyme borreliosis: 221 of the patients with neurological abnormalities and 19 with oligoarticular arthritis. Citrated blood and serum samples were collected from the patients for culture and serological examination, respectively. Moreover, 173 cerebrospinal and 6 synovial fluid samples were tested. New oligonucleotide primers based on B. burgdorferi sensu lato 16SrRNA gene sequences were designed for the detection of the bacteria in blood, cerebrospinal, and synovial fluid specimens with PCR. Levels of specific antibodies were measured in serum, cerebrospinal fluid and synovial fluid samples using ELISA and Western blot. B. burgdorferi spirochetes from blood, cerebrospinal fluid, and synovial fluid samples were cultured in cell line. Extracted and purified B. burgdorferi DNA was identified by PCR with new oligonucleotide primers. Then three genospecies were identified by PCR amplification with other primer sets specific for 16S rDNA and/or by the restriction fragment length polymorphism of 23S(rrl)-5S(rrf). RESULTS: Bacterial DNA were found in samples from 32 patients, including 28 patients with neuroborreliosis and 4 with Lyme arthritis. B. burgdorferi-specific IgM and/or IgG serum antibodies were detected in 14 of these patients. Fourteen strains of Borrelia garini, 4 strains of Borrelia afzelii and 1 strain of B. burgdorferi sensu stricto were identified by PCR. Genospecies were not recognized in 13 specimens. CONCLUSIONS: The procedure can be a rapid and sensitive diagnostic method for the detection of etiological agents in clinical materials derived from patients with the clinical symptoms of Lyme borreliosis. It can be utilized for both basic research as well as routine laboratory diagnosis.     

Cardiovascular effects of ephedrine,caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women

Low caloric diet is a commonly accepted treatment in obesity. However, owing to moderate results, a pharmacological support has been proposed. As some efficacious drugs activate overall sympathetic activity, they might modify functions of the cardiovascular system. Three groups of subjects were studied: (1) nine obese women receiving only a standard hypocaloric diet; (2) nine obese women receiving a standard hypocaloric diet and ephedrine (2 × 25 mg) with caffeine (2 × 200 mg); (3) nine obese women receiving a standard hypocaloric diet and ephedrine (2 × 25 mg) with caffeine (2 × 200 mg) and yohimbine (2 × 5 mg). The cardiovascular state was evaluated by thoracic electrical bioimpedance, automatic sphygmomanometry and continuous ECG recording. In each patient, the haemodynamic study was performed twice: at rest, i.e. before treatment; and after 10 days of treatment. On the same days in each patient, the haemodynamic tests were performed during physical exercises (handgrip stress and cycloergometer exercise). Caffeine and ephedrine had no haemodynamic effect in resting patients. These two drugs led to an increase in ejection fraction during cycloergometer exercise. Addition of yohimbine increased diastolic pressure and heart rate but decreased ejection fraction and stroke index during rest. We also observed that addition of yohimbine decreased ejection fraction during the handgrip and cycloergometer exercise and increased cardiac load during dynamic exercise. Pharmacological supplement of ephedrine and caffeine to a low caloric diet modified the cardiovascular system weakly, but the addition of yohimbine to this regimen attenuated cardiac performance during rest and handgrip and increased cardiac work during dynamic exercise.     

Screening for ALK abnormalities in central nervous system metastases of non‐small‐cell lung cancer

Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3%–7% of primary non‐small‐cell lung cancer (NSCLC) and its presence is commonly associated with adenocarcinoma (AD) type and non‐smoking history. ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed efficiency in patients with primary NSCLC harboring ALK gene rearrangement. Moreover, response to ALK TKIs was observed in central nervous system (CNS) metastatic lesions of NSCLC. However, there are no reports concerning the frequency of ALK rearrangement in CNS metastases. We assessed the frequency of ALK abnormalities in 145 formalin fixed paraffin embedded (FFPE) tissue samples from CNS metastases of NSCLC using immunohistochemical (IHC) automated staining (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH) technique (Abbot Molecular, USA). The studied group was heterogeneous in terms of histopathology and smoking status. ALK abnormalities were detected in 4.8% (7/145) of CNS metastases. ALK abnormalities were observed in six AD (7.5%; 6/80) and in single patients with adenosuqamous lung carcinoma. Analysis of clinical and demographic factors indicated that expression of abnormal ALK was significantly more frequently observed (P = 0.0002; χ² = 16.783) in former‐smokers. Comparison of IHC and FISH results showed some discrepancies, which were caused by unspecific staining of macrophages and glial/nerve cells, which constitute the background of CNS tissues. Their results indicate high frequency of ALK gene rearrangement in CNS metastatic sites of NSCLC that are in line with prior studies concerning evaluation of the presence of ALK abnormalities in such patients. However, they showed that assessment of ALK by IHC and FISH methods in CNS tissues require additional standardizations.     

Total hip replacement using unipolar and bipolar prostheses in the treatment of femoral neck fractures

Background. The trials to replace head and neck hip fractures using allogenic material were undertaken nearly 100 years ago. In 1974 Baterman described the construction of bipolar prosthesis defined as intermediate type between half prosthesis and total prosthesis. Autors present biomechanical aspects of bilateral prosthesis use. Indications for unipolar and bipolar prosthesis implantation in hip fractures were based on therapeutic algorrhythm presented by american authors and "survival" scale presented by Peterborough-Cambridge center. Material and methods. Between 1999 and 2001 there were 218 hip prosthesis implantations performed, including 151 unipolar and 67 bipolar ones. For control check-up presented 47 patients after unipolar and 38 after bipolar prosthesis implantation. The average period of follow up was 26,7 months. Results. Results were interpreted using Merle d'Aubigne's and Postel's scale. The complications observed during follow up were also discussed. Conclusions. Conclusions included the prevalence of bipolar prosthesis compared to unipolar one : increased angle of hip joint mobility, lesser pain and much slower progression of degenerative changes within hip joint.