Energy- and glutathione metabolism in spermatids as possible targets for antispermatogenic agents

It has been reported that a number of drugs and chemicals act preferentially on spermatogenesis (Fox & Fox, 1967; Patanelli, 1975). A specific action of a toxic compound on spermatogenesis suggests a specific target in the testicular tubules and may point to a unique. or at least rare property of spermatogenic cells (or possibly Sertoli cells) as compared with all (other) somatic cell types. As indicated in this Introduction, spermatogenic cells possess a number of particular features. In the present thesis it was studied whether specific biochemical processes in spermatids are possible targets for antispermatogenic agents. Remarkable biochemical properties of advanced spermatogenic cells include the presence of the testis-specific lactate dehydrogenase isoenzyme LDH-C 4 (see 1.2) and the deviating energy metabolism (see 1.2 and Appendix paper). Drugs acting on mitochondria may preferentially kill spermatogenic cells, since these cells are highly dependent on mitochondrial function. In the experiments described in Chapter 2 and 3, effects of the antifertility agent gossypol on LDH-C4 activity and ATP production in spermatids were studied. From the biochemical analysis of the preferential action of gossypol on spermatogenic cells, more can be learned about biochemical processes which are of particular importance in the spermatogenic cells. It was observed that gossypol may interfere with spermatogenesis through an effect on ATP production. In this context, ATP metabolism in spermatids was studied in more detail as described in Chapter 4. Another possible target for antispermatogenic agents is glutathione metabolism in the testicular tubules (see 1.6). In the experiments described in Chapter S, glutathione S-transferase substrates and oxidizing agents were applied to study the presence of GSH-dependent defence mechanisms in round spermatids. In Chapter 6, it is evaluated to what extent the GSH-dependent defence systems in spermatids can provide protection against xenobiotics and the induction of DNA damage by ionizing radiation. The possible role of Sertoli cells in the de novo glutathione biosynthesis in seminiferous tubules is indicated in Chapter 7. In the experiments described in this Chapter 7 the glutathione biosynthesis in isolated testicular cells and tubule fragments was studied, making use of the glutathione-depleting agent diethyl maleate and the glutathione biosynthesis inhibitor buthionine sulfoximine. It is anticipated that improved understanding of the action of different compounds on biochemical processes in Sertoli cells and spermatogenic cells, may provide working hypothesises to test and identify antispermatogenic agent

Real-time quantification and display of skin radiation during coronary angiography and intervention

BACKGROUND: Radiographically guided investigations may be associated with excessive radiation exposure, which may cause skin injuries. The purpose of this study was to develop and test a system that measures in real time the dose applied to each 1-cm(2) area of skin, taking into account the movement of the x-ray source and changes in the beam characteristics. The goal of such a system is to help prevent high doses that might cause skin injury. METHODS AND RESULTS: The entrance point, beam size, and dose at the skin of the patient were calculated by use of the geometrical settings of gantry, investigation table, and x-ray beam and an ionization chamber. The data are displayed graphically. Three hundred twenty-two sequential cardiac investigations in adult patients were analyzed. The mean peak entrance dose per investigation was 0.475 Gy to a mean skin area of 8.2 cm(2). The cumulative KERMA-area product per investigation was 52.2 Gy/cm(2) (25.4 to 99.2 Gy/cm(2)), and the mean entrance beam size at the skin was 49.2 cm(2). Twenty-eight percent of the patients (90/322) received a maximum dose of 2 Gy. CONCLUSIONS: Monitoring of the dose distribution at the skin will alert the operator to the development of high-dose areas; by use of other gantry settings with nonoverlapping entrance fields, different generator settings, and extra collimation, skin lesion can be avoided

Severity of Diabetes Mellitus and Total Hip or Knee Replacement: A Population-Based Case-Control Study

Contains fulltext : 171491.pdf (publisher's version ) (Open Access)It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78-0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes

The Psychobiology of Authentic and Simulated Dissociative Personality States:The Full Monty

The etiology of dissociative identity disorder (DID) remains a topic of debate. Proponents of the fantasy model and the trauma model of DID have both called for more empirical research. To this end, the current study presents new and extended data analyses of a previously published (H2O)-O-15 positron emission tomography imaging study. This study included 29 subjects: 11 patients with DID and 10 high- and 8 low-fantasy-prone DID-simulating mentally healthy control subjects. All subjects underwent an autobiographical memory script-driven (neutral and trauma related) imagery paradigm in 2 (simulated) dissociative personality states (neutral and trauma related). Psychobiological and psychophysiological data were obtained. Results of the new post-hoc tests on the psychophysiological responses support the trauma model. New results of the brain imaging data did not support the fantasy model. This study extends previously published results by offering important new supporting data for the trauma model of DID.</p

To what extent does the securitisation of asylum seekers contribute to Australia’s failure to meet its relevant international human rights obligations?

BACKGROUND: Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the association between plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) concentrations and cognitive functioning in late-life depression, including the potentially moderating role of sex. METHODS: A total of 369 depressed older persons (>/=60 years) from The Netherlands study of Depression in Older persons (NESDO) were included. Four cognitive domains, i.e. verbal memory, processing speed, interference control and attention were assessed with three cognitive tests (Stroop test, Wais Digit span test, and Rey's verbal learning test). Multiple linear regression analyses were applied with the four cognitive domains as dependent variables adjusted for confounders. RESULTS: The association between NGAL levels and specific cognitive domains were sex-specific. In women, higher NGAL levels were associated with impaired verbal memory and lower processing speed. In men, higher NGAL levels were associated with worse interference control. Higher NGAL levels were not associated with attention. No sex-specific associations of either high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) with cognitive functioning were found. CONCLUSION: This study shows sex-specific association of NGAL with cognitive functioning in late-life depression

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet ag

Severity of Diabetes Mellitus and Total Hip or Knee Replacement

Permissions RESEARCH ARTICLE: OBSERVATIONAL STUDY Severity of Diabetes Mellitus and Total Hip or Knee Replacement A Population-Based Case–Control Study Nielen, Johannes T.H. MSc; Emans, Pieter J. PhD; Dagnelie, Pieter C. PhD; Boonen, Annelies PhD; Lalmohamed, Arief PhD; de Boer, Anthonius PhD; van den Bemt, Bart J.F. PhD; de Vries, Frank PhD Editor(s): Roever., Leonardo Author Information Medicine 95(20):p e3739, May 2016. | DOI: 10.1097/MD.0000000000003739 OPEN SDC Metrics Abstract It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality. To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity. A population-based case–control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity. Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78–0.94)) and THR (OR = 0.90 (95% CI = 0.82–0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c. This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes