Involvement of human monogenic cardiomyopathy genes in experimental polygenic cardiac hypertrophy.

Hypertrophic cardiomyopathy thickens heart muscles, reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure, to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole genome of 13-wk-old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at 5 ages (2 days old and 4, 13, 33, and 50 wk old) compared with human idiopathic dilated cardiomyopathy data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-day-old HHR and age-matched NHR. We also investigated experimentally validated microRNA-mRNA interactions. Whole-genome sequencing revealed unique variants mostly located in noncoding regions of HHR and NHR. We found 29 genes differentially expressed in at least 1 age. Genes encoding desmoglein 2 ( Dsg2) and transthyretin ( Ttr) were significantly differentially expressed at all ages in the HHR, but only Ttr was also differentially expressed in human idiopathic cardiomyopathy. Lastly, only two microRNAs differentially expressed in the HHR were present in our comparison of validated microRNA-mRNA interactions. These two microRNAs interact with five of the genes studied. Our study shows that genes involved in monogenic forms of human cardiomyopathies may also influence polygenic forms of the disease.

Optically Controlled Orbital Angular Momentum Generation in a Polaritonic Quantum Fluid.

Applications of the orbital angular momentum (OAM) of light range from the next generation of optical communication systems to optical imaging and optical manipulation of particles. Here we propose a micron-sized semiconductor source that emits light with predefined OAM pairs. This source is based on a polaritonic quantum fluid. We show how in this system modulational instabilities can be controlled and harnessed for the spontaneous formation of OAM pairs not present in the pump laser source. Once created, the OAM states exhibit exotic flow patterns in the quantum fluid, characterized by generation-annihilation pairs. These can only occur in open systems, not in equilibrium condensates, in contrast to well-established vortex-antivortex pairs.

Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk.

Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 µg/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.

Marine polyunsaturated fatty acids and cancer therapy.

Polyunsaturated fatty acids (PUFAs) derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely consumed as supplements within the community. However, the use of marine PUFAs in a therapeutic context is also increasing in patients receiving treatment for a range of cancer types. On balance, the literature suggests that marine PUFAs have potential as an effective adjuvant to chemotherapy treatment, may have direct anticancer effects, and may help ameliorate some of the secondary complications associated with cancer. Although a range of doses have been trialled, it would appear that supplementation of fish oil (>3 g per day) or EPA/DHA (>1 g EPA and >0.8 g DHA per day) is associated with positive clinical outcomes. However, further research is still required to determine the mechanisms via which marine PUFAs are mediating their effects. This review summarises our current understanding of marine PUFAs and cancer therapy.

Effect of rugby training on blood antioxidant defenses in able-bodied and spinal cord injured players.

STUDY DESIGN: A cross-sectional study with comparison group. OBJECTIVES: To examine the effect of rugby training on the blood antioxidant capacity in able-bodied and wheelchair rugby players with tetraplegia. SETTING: Poland. METHODS: Four groups of subjects participated in the study: sedentary able-bodied males (group SA, n=19), sedentary males with tetraplegia (group ST, n=10), able-bodied rugby players (group RA, n=22) and wheelchair rugby players with tetraplegia (group RT, n=14). The activities of superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT) were determined in erythrocyte hemolysates, whereas glutathione peroxidase (GPX) activity was determined in whole-blood hemolysates. Concentrations of total antioxidant status (TAS) was determined in plasma. RESULTS: SOD activity was significantly higher in the group SA compared with group ST and group RA. No significant differences occurred within the tetraplegic groups: RT and ST. Resting CAT and GPX activities were significantly higher in both the groups of rugby players than in the respective group of sedentary males. There were no differences in GR activity among all the studied groups. Plasma TAS concentration was higher in both the groups of able-bodied males compared with the respective groups of tetraplegics. The present study is the first to conduct an evaluation of wheelchair rugby training-induced adaptations to oxidative stress in individuals with tetraplegia. CONCLUSION: Adaptive response to training was similar in both able-bodied and wheelchair rugby players, and it was characterized by increased erythrocyte CAT and GPX activities in resting conditions improving resistance to oxidative stress.

Serum progesterone concentrations on the day of oocyte retrieval above 9.23 ng/ml may predict ovarian hyperstimulation syndrome risk in in vitro fertilized patients.

The aim of our study was to evaluate serum progesterone levels on the day of oocyte retrieval as a promising biomarker inorder to evaluate the risk of ovarian hyperstimulation syndrome in a group with controlled ovarian hyperstimulation protocols using either gonadotropin antagonists or agonists (GnRH), compare with a natural cycle control group. Patients were divided into 3 groups (148 patients in total): control group in the natural cycle, patients treated with GnRH agonist and patients treated with GnRH antagonist. When we compared both controlled ovarian hyperstimulation (COH) protocol groups with the control group, we found statistically higher levels of progesterone in patients after COH (control versus long protocol group: 1.43 ± 1.28 ng/ml versus 8.95 ± 5.95 ng/ml; P < 0.001; control versus GnRH antagonist group: 1.43 ± 1.28 ng/ml versus 7.18 ± 5.13 ng/ml; P < 0.001). According to receiver operating characteristic (ROC) analysis, the level of serum progesterone on the day of oocyte retrieval, above which the risk of ovarian hyperstimulation syndrome (OHSS) is associated with a more than fourfold higher risk (OR 4.24; 95% CI 2.6 - 6.9) was found to be 9.23 ng/ml, with AUC: 0.896, P = 0.026 (95% CI 0.845 - 0.947). Progesterone level on the day of oocyte retrieval may be used as an additional sensitivity marker in treatment of early forms as well by freezing of embryos in prevention of late forms of OHSS.

High levels of soluble vascular endothelial growth factor receptor 1/sFlt1 and low levels of vascular endothelial growth factor in follicular fluid on the day of oocyte retrieval correlate with ovarian hyperstimulation syndrom regardless of the stimulation protocol.

The aim of the study was to assess the predictive value of vascular endothelial growth factor (VEGF), its soluble receptor - sVEGF-R1/sFlt1 and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in serum and follicular fluid (FF) for ovarian hyperstimulation syndrome (OHSS) in women undergoing controlled ovarian hyperstimulation (COH) protocols. Patients have been divided into 3 groups: control group on natural cycle, patients stimulated with GnRH agonist and patients stimulated with GnRH antagonist. The FF and serum concentrations of VEGF, EG-VEGF, sVEGF R1 and the expression of VEGF and EG-VEGF mRNA in GC in small and large follicles collected from patients were investigated. When we compared all patients in a trial, OHSS occurrence was correlated with higher level of sVEGF R1 and a lower level of VEGF in a follicular fluid from large follicles in a day of oocyte retrieval. The VEGF/sVEGF-R1 ratio for patients in COH groups, above which the risk of developing OHSS is very low (OR 0.1 (95% CI 0.01 - 0.29, P = 0.0006) was found to be 0.281 pg/ml, with AUC - 0.738, P = 0.042, (95% CI 0.656 - 0.82). High levels of sVEGF-R1 and low level of VEGF in FF on the day of oocyte retrieval correlate with OHSS regardless of the stimulation protocol.

The use of oxidative stress biomarkers in live animals (in vivo) to predict meat quality deterioration postmortem (in vitro) caused by changes in muscle biochemical components.

This study was conducted to determine whether circulating concentrations of blood isoprostanes can be used as an effective biomarker in lambs to predict degradation of color and/or lipid stability in meat. Lambs ( = 84) were fed diets of either lucerne pasture, annual ryegrass pasture, a commercial feedlot pellet, or a combination of annual ryegrass and feedlot pellet for 8 wk, including a 2-wk adaptation period. Blood isoprostane concentration at wk 0, 4, 6 or 8 of feeding was determined. Blood isoprostane concentration for each animal was then correlated with muscle biochemical components that impact color and/or lipid oxidative status during retail display. This included lipid oxidation levels in muscle assessed by thiobarbituric acid reactive substances and meat redness determined by a HunterLab colorimetric spectrometer. Lambs that consumed the commercial feedlot pellet had a lower muscle vitamin E level (< 0.01) and a greater level of -6 PUFA ( < 0.001) compared with lambs finished on annual ryegrass or lucerne. Lipid oxidation levels were greatest for lambs finished on the feedlot ration, lowest in lambs finished on the ryegrass diet, and intermediate for lambs finished on lucerne and ryegrass-feedlot combination ( < 0.01). After 8 wk of feeding, blood isoprostane concentration was positively correlated with lipid oxidation of meat displayed for 72 h in simulated retail conditions ( < 0.01). There was a negative linear relationship between isoprostane concentration and muscle vitamin E concentration ( = 0.07), lipid oxidation and muscle vitamin E concentration ( < 0.01) but a positive linear relationship between isoprostane concentration and muscle -6 PUFA ( < 0.001) or lipid oxidation and muscle -6 PUFA concentration ( < 0.001). Blood isoprostane concentration and lipid oxidation in meat were influenced by muscle vitamin E and -6 PUFA but not by -3 PUFA. There was no significant relationship observed between blood isoprostane concentration at 0, 4, 6 or 8 wk feeding vs. overall meat color (redness of meat) at 0 and 72 h of display, stored under simulated retail conditions. The results indicate that circulating blood isoprostane concentration can be a useful tool to predict the oxidative status of postmortem meat. Future work will examine the impact of this relationship on meat flavor/aroma deterioration post farm.

Impact of obesity and leptin treatment on adipocyte gene expression in Psammomys obesus.

We examined the effects of leptin treatment on the expression of key genes in adipocyte metabolism in Psammomys obesus (P. obesus), a polygenic rodent model of obesity. Lean and obese P. obesus were given three daily intraperitoneal injections of either saline or leptin (total of 45 mg/kg per day) for 7 days. In lean animals, leptin treatment led to reductions in food intake, body weight and fat mass. Pair-fed animals matched for the reduction in food intake of the lean leptin-treated animals demonstrated similar reductions in body weight and fat mass. In obese P. obesus, leptin treatment failed to have any effect on body weight or body fat mass, indicating leptin resistance. Lipoprotein lipase, hormone-sensitive lipase and peroxisome proliferator activated receptor gamma 2 mRNA levels were significantly reduced in lean leptin-treated animals, whereas pair-fed animals were similar to lean controls. Uncoupling protein 2 and glycerol phosphate acyltransferase were also reduced in the lean leptin-treated animals, but not significantly so. Obese animals did not show any gene expression changes after leptin treatment. In conclusion, high circulating concentrations of leptin in lean P. obesus resulted in decreased gene expression of a number of key lipid enzymes, independent of changes in food intake, body weight and fat mass. These effects of leptin were not found in obese P. obesus.

Total hip arthroplasty using porous-coated femoral components in patients with rheumatoid arthritis.

We studied the results of total hip arthroplasty (THA) using AML porous-coated femoral components at a mean follow-up of 11 years in a non-selected, consecutive series of patients with rheumatoid arthritis. We reviewed 64 patients with 82 primary THAs using these components. There were seven men (8 hips) and 57 women (74 hips) with a mean age of 55.1 years (24 to 80) at the time of surgery. Nine patients (11 hips) died before the two-year follow-up. Of the remaining 71 hips, only one stem was revised for aseptic loosening. Survivorship for the stems was 98.1% (95% confidence interval (CI) 94.5 to 100.0) at ten years, using a life-table analysis, with revision for any reason as an endpoint. Of the 70 unrevised stems, 66 (94%) had bony ingrowth, while four (6%) were radiologically loose at the most recent follow-up (mean 11.4 years). Our study shows the excellent long-term results which can be achieved with porous-coated femoral components in patients with rheumatoid arthritis.

Risk evaluation of ventricular tachycardia using wavelet transform irregularity of the high-resolution electrocardiogram.

A new method for analysis of high-resolution ECG signals using a wavelet transform based on a modified Morlet function is presented. A polynomial filter is used to reduce low-frequency, high-amplitude noise components in the analysed signals. The method is tested on test ECG signals with simulated late potentials and finally verified on two post-infarction patient (PP) groups: 62 PPs with ventricular tachycardia and 44 PPs without arrhythmia. A new quantitative parameter, the irregularity factor, is proposed for discrimination between the study groups. The results show a significant difference in the parameter values for tachycardia patients compared with those for patients without arrhythmia. The sensitivity of the proposed method is 85%, and the specificity is 93%.

Spectral analysis of laser-Doppler perfusion signal measured during thermal test.

The method of spectral analysis of laser-Doppler perfusion signal measured during thermal test is proposed. During three 20 min phases with 40, 5, and 40 degrees C of thermal test laser-Doppler perfusion signal was recorded. For each signal phase frequency spectra were calculated using the FFT method. Quantitative parameter Spectral Factor for results evaluation was proposed. In total 94 patients were measured: 69 with Raynaud's phenomenon and 25 normal subjects. Additionally in 18 Raynaud's patients the influence of Nifedipine was studied. Results suggest that proposed parameter is able to differentiate between Raynaud's patients and normal subjects and that is useful for evaluation of Nifedipine effectiveness. However, further studies are needed to improve the method to differentiate between primary and secondary Raynaud's patients.

[Percutaneous sperm retrieval for ICSI procedures in men with obstructive azoospermia: ICSI-PESA and ICSI-TESE micromanipulation: our experience]. / Wlasne doswiadczenia w przezskórnym pozyskiwaniu plemników do zaplodnienia pozaustrojowego ICSI-PESA oraz ICSI-TESE u mezczyzn z azoospermia obstrukcyjna.

OBJECTIVES: The sperm retrieval for ICSI procedures is possibly using following procedures: ejaculate sperm, epididymal sperm obtained by microsurgical aspiration or percutaneous puncture and testicular sperm that are obtained by surgical excision or percutaneous biopsy. Percutaneous techniques seem to be rather simple and effective procedures. DESIGN: The authors present their own experiences with percutaneous sperm retrieval for micromanipulation ICSI from the epididymis (ICSI-PESA) and from the testicular tissue (ICSI-TESE) in men with obstructive azoospermia and with reactive impotence. First time in Poland ICSI-PESA was done on April 11, 1996 in Private Infertility Center "Novum", Warsaw. MATERIAL AND METHODS: From April 1996 to the end of January 1998, 10 ICSI-PESA procedures (in 9 couples) and 8 ICSI-TESE (in 6 couples) were performed. In one case ICSI-PESA was performed in man with psychological inability of masturbation during his wife's IVF protocol. All procedures were performed as the day case urology, under general anesthesia. The fine needles No 6 in PESA or biopsy needle from Hepafix Set B. Braun in TESE were used. The therapy of antibiotic and common analgesic drug was used routinely after puncture. RESULTS: The effectiveness of obtaining sperm for micromanipulation were 100% ICSI-PESA and 75% ICSI-TESE. The pregnancy rate in PESA was 50% and 5 healthy children were born. In TESE only 1 woman (17%) was pregnant, but early spontaneous miscarriage was reported. No surgical and anesthesiological complications were noticed. CONCLUSIONS: Obtaining sperm for micromanipulation ICSI using percutaneous epididymal puncture or testicular tissue needle biopsy seems to be effective and safe for patients with obstructive azoospermia or reactive impotence.

[Needle testicular biopsy in the diagnosis of male infertility]. / Iglowa biopsja jader w diagnostyce nieplodnosci meskiej.

OBJECTIVES: Evaluation of testicular tissue is very important diagnostic procedures in cryptozoospermia and azoospermia. It is verified the patient for treatment (stimulation spermatogenesis), for micromanipulation ICSI or for insemination donor semen procedure. Surgical biopsy is very popular between andrologist and urologist, but needle biopsy seems to be easier and safer. DESIGN: The authors present their experience with needle testicular biopsy during the diagnosis patients with azoospermia or cryptozoospermia and the men with paraplegia after trauma and without ejaculation. MATERIAL AND METHODS: The study group included 63 biopsies in 58 men with azoospermia and severe oligoasthenozoospermia (cryptozoospermia) and 2 with paraplegia. The specimens were taken from 125 testes under general anesthesia (i.v-Diprivan, Propofol, Zeneca and Fentanyl) using biopsy needle from Hepafix B. Braun Melsungen, Germany. All procedures were performed as a day case. RESULTS: In 95% specimens were adequate for histopathological investigations and for planning the treatment. Only one complication (0, 8%) -small haematoma testis was observed. CONCLUSIONS: The needle biopsy of testicular tissue is sufficiency in histopathological examination, safe for patients and easy for urologists. The total cost is much more lower than cost of surgical biopsy.

[Lipid disturbance of cell membranes in the etiopathogenesis of schizophrenia and affective disorders]. / Zaburzenia lipidów blon komórkowych w etiopatogenezie schizofrenii i chorób afektywnych.

The authors present information on the key role of lipid disturbances (mainly phospholipids) of neural membranes in the etiopathogenesis of schizophrenia and affective disorders. Current theories on membrane phospholipid disturbances in the etiopathogenesis of schizophrenia and affective disorders are connected to the idea that the primary metabolic disorder in both these disorders is due to the altered activity of phospholipase AZ, which in turn brings about disturbances in other lipid elements. Especially the functional insufficiency of some necessary fatty acids, as well as disturbed prostaglandin secretion has been shown in these disorders. In the recent years evidence has been collected on the action of pharmacologic substances used in these disorders on the lipid enzyme metabolism.

[Angioid streaks--case report]. / Pasma naczyniaste--opis przypadku.

A case of a 46-year-old, generally healthy man, with sudden deterioration of visual acuity associated with macular haemorrhagies is presented. Angioid streaks were diagnosed basing on the ophthalmoscopical and angiographic picture of the fundus.

[Evaluation of pupillary reaction to light flash in patients with retinitis pigmentosa]. / Ocena reakcji zrenicy na blysk swietlny u pacjentów ze zwyrodnieniem barwnikowym siatkówki.

Twenty four patients with retinal pigment dystrophy were subjected to examination of pupillary reaction. Evaluated was the amplitude of pupillary reaction on a standard light flash. The results received were compared with the field changes. It was noted that the amplitude is diminished depending on the changes in the visual field.

[Effect of complex treatment of retinitis pigmentosa on the results of pupillography]. / Wplyw kompleksowego leczenia zwyrodnienia barwnikowego siatkówki na wynik pupillografii.

Presented are the results of a 3 years long observation of the pupillary reaction in patients with pigmentary retinal dystrophy who have been subjected to a complex treatment. The authors discovered a consistency between the changes in the visual field and the amplitude of the pupillary reaction.

[Pemphigoid as a cause of marked impairment of visual acuity]. / Pemphigoid jako przyczyna znacznego uposledzenia ostrosci wzroku.

Among 11 patients aged 9-79 years with diagnosed pemphigoid 5 were men and 6 women. Three persons exhibited only some conjunctival irritation and conjunctival adhesions, the remaining 8--besides some shallowness of the fornices--showed also corneal changes. Six patients showed signs of the dry-eye syndrome and 3--symptoms of secondary glaucoma. General treatment (Avlosulfon, encorton) was applied in 8 patients.