QSAR studies on a number of pyrrolidin-2-one antiarrhythmic arylpiperazinyls

The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure–activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors

Long-Term Effects of the Periconception Period on Embryo Epigenetic Profile and Phenotype: The Role of Stress and How This Effect Is Mediated

Stress represents an unavoidable aspect of human life, and pathologies associated with dysregulation of stress mechanisms - particularly psychiatric disorders - represent a significant global health problem. While it has long been observed that levels of stress experienced in the periconception period may greatly affect the offspring's risk of psychiatric disorders, the mechanisms underlying these associations are not yet comprehensively understood. In order to address this question, this chapter will take a 'top-down' approach, by first defining stress and associated concepts, before exploring the mechanistic basis of the stress response in the form of the hypothalamic-pituitary-adrenal (HPA) axis, and how dysregulation of the HPA axis can impede our mental and physical health, primarily via imbalances in glucocorticoids (GCs) and their corresponding receptors (GRs) in the brain. The current extent of knowledge pertaining to the impact of stress on developmental programming and epigenetic inheritance is then extensively discussed, including the role of chromatin remodelling associated with specific HPA axis-related genes and the possible role of regulatory RNAs as messengers of environmental stress both in the intrauterine environment and across the germ line. Furthering our understanding of the role of stress on embryonic development is crucial if we are to increase our predictive power of disease risk and devise-effective treatments and intervention strategies

Causes, consequences and biomarkers of stress in swine: an update

BACKGROUND: In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. CONCLUSIONS: Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms

Haematuria: a long-term problem after prostatectomy.

OBJECTIVE: The causes of 'late' haematuria (2 years or more) following endoscopic and open prostatectomy were studied. METHODS: Between 1994 and 1996, more than 400 patients were evaluated for haematuria. Ninety patients with post-prostatectomy haematuria were investigated with upper tract imaging and cystoscopic examination. Amongst these 90 patients, 30 presented with haematuria within 2 years of surgery. These patients were excluded from the study as they had normal investigations. RESULTS: Of these 60 patients, 24 (43%) had demonstrable causes of haematuria in their urinary tract. Six of them had urinary tract malignancy. CONCLUSIONS: There is a substantial likelihood of finding a cause for haematuria in patients who had prostatectomy even though they had full-scale urological investigations before. There is a need, therefore, to carry out necessary screening investigations in such patients

The role of the prostate in male fertility, health and disease

Ejaculation is a synchronized cascade of events that has the ultimate goal of activating sperm and enabling them to reach an egg for fertilization. The seminal plasma contains a complex mixture of fluids that is secreted from the testes, epididymis and male accessory glands. The prostate gland has a pivotal role in this process, as prostatic fluid enriched in Zn(2+), citrate and kallikreins is crucial for the molecular synchronization of the functional cascade triggered by ejaculatory stimuli. The prostate is the target of a number of common diseases that can affect male fertility at different ages. In both young and aged men, prostatic diseases or an unhealthy prostate can affect spermatozoa functioning and, therefore, male fertility. Consideration of prostate physiology emphasizes a number of points: the central role of Zn(2+) and citrate in the regulation of prostate epithelium homeostasis and in ejaculation; the influence of bacteria-related prostatic inflammation on male fertility; and the potential role of prostatic inflammation in promoting the development of prostatic hyperplastic growth and carcinogenesis