Physical efficiency and activity energy expenditure in term pregnancy females measured during cardiopulmonary exercise tests with a supine cycle ergometer

Objectives: To evaluate physical efficiency and activity energy expenditure (AEE) in term pregnancy females during cardiopulmonary exercise tests with a supine cycle ergometer.

Material and methods: The study comprised 22 healthy full-term pregnancy women with uncomplicated pregnancies hospitalized in the Department of Gynecology and Obstetrics, Specialist Teaching Hospital in Tychy, Poland. All subjects underwent cardiopulmonary exercise tests (CPET) on a supine cycle ergometer. The 12-min, three-stage, progressive, symptom-limited submaximal test protocol (up to 80% HR_max) was used. Pulsometry was used to record HR on a beat-to-beat analysis and to calculate AEE. Respiratory responses were measured by ergospirometer and a computer system on a breath-by-breath basis at rest, during exercise and at restitution.

Results: In the studied population, VO_2max was established at the level of 2.19?±?0.33?L/min in ergospirometry and 2.04?±?025?L/min in pulsometry. Physical efficiency calculated for sub-maximal exercise by use of the Davis equation was 30.52?±?0.12%. AEE, based on VO₂ in various phases of the CPET, was 0.47, 0.71 and 0.88?L/min for phases 25, 50 and 75 W. Based on ergospirometer readouts, AEE was 10.60, 16.11 and 20.94?kJ/min for phases 25, 50 and 75 W. Overall mean AEE (determined by pulsometry) was 10.59 kJ/min. CPET testing did not have any negative effect upon the health or life of the neonates involved in the study.

Conclusions: Submaximal CPET up to 80% HR_max with a supine cycle ergometer is a safe and precise method for assessing work efficiency in term pregnancy women.     

Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p?=?0.018) and E-sel (p?=?0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p?=?0.005), but not E-sel (p?=?0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p?=?0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.     

Nebulized pentoxifylline for prevention of bronchopulmonary dysplasia in very low birth weight infants: a pilot clinical study.

OBJECTIVE: To evaluate the effectiveness of nebulized pentoxifylline (PTXF) compared to intravenous dexamethasone (DX) or placebo (nebulized distilled water) for the prevention of bronchopulmonary dysplasia (BPD). METHODS: One hundred and fifty very low birth weight infants were randomly assigned to three groups. Entry criteria were the need for oxygen administration on the fourth day of life, irrespective of whether ventilatory support was required. PTXF was administered with a nebulizer every 6 hours on three consecutive days (a single course) in a dose of 20 mg/kg when infants were breathing spontaneously or 10 mg/kg when they needed ventilatory support. DX was given every 12 hours on three consecutive days in a dose of 0.25 mg/kg. Nebulized distilled water was administered with the schedule of inhalation as in the PTXF group. When the need for ventilatory support or oxygen dependency persisted, the course of both drugs and placebo administration was repeated every seven days until the diagnosis of BPD was established. RESULTS: Both PTXF and DX reduced the incidence of disease when compared with placebo. The respective data obtained for the PTXF-group versus the placebo group were as follows: difference in risk, 27%; OR: 0.32; CI: 0.11-0.94; p = 0.039; whereas the results for the DX-group versus the placebo group were: difference in risk, - 23%; OR: 0.39; CI: 0.14-1.14; p = 0.07. CONCLUSION: Our data show that nebulized PTXF reduces the risk of BPD and may be a potential alternative to steroids in the prevention of this disease.     

The role of apelin in central cardiovascular regulation in rats with post‐infarct heart failure maintained on a normal fat or high fat diet

Based on the available literature, it can be assumed that in cases of post‐infarct heart failure (HF) and obesity, a significant change in the central regulation of the cardiovascular system takes place with, among others, the involvement of the apelinergic system. The main objective of the present study was to clarify the role of apelin‐13 in the central regulation of the cardiovascular system in Sprague Dawley rats with HF or sham operated (SO) and fed on a normal fat (NFD) or a high fat diet (HFD). The study was divided into two parts: Part I, hemodynamic studies; and Part II, biochemical and molecular studies. The animals were subjected to the following research procedures. Part I and II: feeding NFD or HFD; experimental induction of HF or SO; Part I: intracerebroventricular (ICV) infusion of the examined substances, monitoring of mean arterial blood pressure (MABP) and heart rate (HR); Part II: venous blood and tissue samples collected. ICV infusion of apelin‐13 caused significantly higher changes in ΔMABP in the SO NFD group. No changes were noted in ΔHR in any of the studied groups. Apelin and apelin receptor (APJ) mRNA expression in the brain and adipose tissues was higher in the HF rats. HFD causes significant increase in expression of apelin and APJ mRNA in the left ventricle. In conclusion, HF and HFD appear to play an important role in modifying the activity of the central apelinergic system and significant changes in mRNA expression of apelin and APJ receptor.     

New amides of 5-(4-chlorobenzoyl)aminoorotic acid: their synthesis and biological activity

The synthesis and in-vitro biological evaluation of the amide series 4 of 5-(4-chlorobenzoyl)aminoorotic acid 2 are presented. The biological properties of a few 5-(4-chlorobenzoyl)amino-2,6-dihydroxy-N-substituted-4-pyrimidinecarboxamide derivatives 4 tested here were compared with those of the isosteric isothiazole derivative MR-2/94 (5-(4-chlorobenzoyl)amino-N-(4-chlorophenyl)-3-methyl-4-isothiazolecarboxamide), which possesses a strong immunosuppressive and anti-inflammatory activity [1, 2], It must be suggested that replacement of the isothiazole by a pyrimidine core ring system resulted in considerable lowering of the anti-inflammatory and immunotropic actions of the obtained amides. Physicochemical properties of 2-(4-chlorophenyl)-6,8-dihydroxy-4H-pyrimido[5,4-d]-1,3-oxazin-4-on 3 are also briefly described.     

Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration. To find out whether caffeine aggravates MDMA neurotoxicity, the content of DA and 5-HT, density of brain DAT and SERT, and oxidative damage of nuclear DNA were determined. Furthermore, the effect of caffeine on MDMA-induced changes in striatal dynorphin and enkephalin and on behavior was assessed. The DA and 5-HT release was determined with in vivo microdialysis, and the monoamine contents were measured by HPLC with electrochemical detection. DNA damage was assayed with the alkaline comet assay. DAT and SERT densities were determined by immunohistochemistry, while prodynorphin (PDYN) and proenkephalin were determined by quantitative PCR reactions. The behavioral changes were measured by the open-field (OF) test and novel object recognition (NOR) test. Caffeine potentiated MDMA-induced DA release while inhibiting 5-HT release in the mouse striatum. Caffeine also exacerbated the oxidative damage of nuclear DNA induced by MDMA but diminished DAT decrease in the striatum and worsened a decrease in SERT density produced by MDMA in the frontal cortex. Neither the striatal PDYN expression, increased by MDMA, nor exploratory and locomotor activities of mice, decreased by MDMA, were affected by caffeine. The exploration of novel object in the NOR test was diminished by MDMA and caffeine. Our data provide evidence that long-term caffeine administration has a powerful influence on functions of dopaminergic and serotonergic neurons in the mouse brain and on neurotoxic effects evoked by MDMA.     

Human papillomavirus infection predicts a better survival rate in patients with oropharyngeal cancer

IntroductionSquamous cell carcinoma is the most common malignant tumour occurring in the head and neck region. It is now understood that (human papillomavirus (HPV)- positive and HPV-negative diseases are two very different clinical entities associated with different outcomes. We decided to assess p16 expression status in patients with oropharyngeal cancer and retrospectively evaluate the outcomes of the treatment.Material and methodsThe evaluated group consisted of 98 consecutive patients with squamous cell carcinoma of the oropharynx treated in a combined way in Holycross Cancer Centre in Kielce in 2006–2014. For all patients p16 status was assessed based on the biological material. In 51 patients HPV infection was diagnosed. The Kaplan-Meier method was used to produce survival curves using the log-rank test and the Cox proportional hazard model was used to determine the risk factors. The following risk factors were included: HPV status (positive, negative), sex, age, smoking, histopathological grade of the tumour, clinical stage, and systemic therapy application. For HPV-positive and HPV-negative patients independent analyses were done including aforementioned factors, excluding HPV status.ResultsThe observation time for HPV-positive patients was significantly longer (p = 0.0008). Fifty-eight patients died, 40 patients are alive. Number of deaths in HPV-negative patients was statistically significantly higher (p = 0.0222). A statistically significant difference in the disease-free survival probability and overall survival probability between HPV-positive and HPV-negative patients was found (p = 0.0045 and p = 0.0037 respectively). For disease-free survival a statistically significant factor of the risk of recurrence was HPV infection (p = 0.0169). For HPV-positive patients, age (p = 0.0199) and smoking (p = 0.0353) were statistically significant risk factors of recurrence. For HPV-negative patients significant risk factors of recurrence were clinical stage (p = 0.0114) and systemic therapy application (p = 0.0271). For overall survival for the entire group statistically significant risk factors were absence of HPV infection (p = 0.0123), male sex (p = 0.0426), and age (p = 0.0311). For HPV-positive patients, age (p = 0.0096) and smoking (p = 0.0387) were statistically significant risk factors of death. For HPV-negative patients significant risk factors of death were clinical stage (p = 0.0120) and systemic therapy application (p = 0.0460).ConclusionsOur data show that HPV infection is a predictor of better disease-free and overall survival in patients with oropharyngeal cancer. For HPV-positive oropharyngeal cancer patients weekly given cisplatin with concurrent radiotherapy can be an alternative to three weekly given cisplatin considering effectiveness and early toxicity.     

The probability of finding nerve branches to the external anal sphincter

Introduction  Normal defecation is a combination of several elements of reflex and voluntary functions. The issue of external anal sphincter innervation is of theoretical and clinical significance; however, literature on the subject is still scarce. Most study reports discuss the course of the pudendal nerve with no close insight into inferior rectal nerves supply to the external anal sphincter. We have not found any statistical “mapping” of the site of the nerve branches insertion into the external anal sphincter. Thus, the purpose of the present study was to determine the least and most typical location of nerve branches to the external anal sphincter. One hundred and ten pudendal nerve preparations were analysed. Following the dissection of the pudendal nerve and its branches, a beam compass was used to take linear measurements from the apex of the coccygeal bone to the point of nerve branch insertion to the external anal sphincter. The distance between coccygeal bone apex and the central tendon of the perineum was also measured. For the purpose of comparison, results are presented as relative Bi/A values. Computer programmes devised by the author of this paper within Turbo Pascal were then used to determine the probability of finding nerve branches to the external anal sphincter. Results  Based on the analysis of 110 preparations of the pudendal nerve and its branches, one might conclude that the former was the main although not necessarily the only source of external anal sphincter innervation. While analysing the most and the least probable location of nerve branches to the external anal sphincter, the muscle length was expressed as percentage, i.e., 0% of sphincter length = the apex of the coccygeal bone; 100% of sphincter length = the central tendon of the perineum. The length was then divided into 5% intervals with the probability of finding nerve branches determined by programmes written in Pascal. Within 30–85% of external anal sphincter length, the probability of finding nerve branches to the external anal sphincter is greater than 0.3 with peak probability of 0.68 in the interval between 55 and 65%. Discussion  Sphincter innervation and clinicoanatomical function of anal canal closure apparatus has been discussed with reference to external anal sphincter injury. Transcutaneous electrostimulation of the pudendal nerve and the use of anal canal electrodes have also been mentioned. Conclusions  The most probable location of nerve branches to the external anal sphincter is half way of its length, i.e., at hour 3 or 9 of the knee-elbow position or lithotomy position. The external anal sphincter can also be directly supplied by nerve branches originating from the sacral nerve root S4; the branches then go towards the posterior part of the sphincter.