Effects of Steroid Hormones on Sex Differences in Cerebral Perfusion

Sex differences in the brain appear to play an important role in the prevalence and progression of various neuropsychiatric disorders, but to date little is known about the cerebral mechanisms underlying these differences. One widely reported finding is that women demonstrate higher cerebral perfusion than men, but the underlying cause of this difference in perfusion is not known. This study investigated the putative role of steroid hormones such as oestradiol, testosterone, and dehydroepiandrosterone sulphate (DHEAS) as underlying factors influencing cerebral perfusion. We acquired arterial spin labelling perfusion images of 36 healthy adult subjects (16 men, 20 women). Analyses on average whole brain perfusion levels included a multiple regression analysis to test for the relative impact of each hormone on the global perfusion. Additionally, voxel-based analyses were performed to investigate the sex difference in regional perfusion as well as the correlations between local perfusion and serum oestradiol, testosterone, and DHEAS concentrations. Our results replicated the known sex difference in perfusion, with women showing significantly higher global and regional perfusion. For the global perfusion, DHEAS was the only significant predictor amongst the steroid hormones, showing a strong negative correlation with cerebral perfusion. The voxel-based analyses revealed modest sex-dependent correlations between local perfusion and testosterone, in addition to a strong modulatory effect of DHEAS in cortical, subcortical, and cerebellar regions. We conclude that DHEAS in particular may play an important role as an underlying factor driving the difference in cerebral perfusion between men and women.     

Vagal Withdrawal and Susceptibility to Cardiac Arrhythmias in Rats with High Trait Aggressiveness

Personality characteristics, e.g. aggressiveness, have long been associated with an increased risk of cardiac disease. However, the underlying mechanisms remain unclear. In this study we used a rodent model for characterizing cardiac autonomic modulation in rats that differ widely in their level of aggressive behavior. To reach this goal, high-aggressive (HA, n = 10) and non-aggressive (NA, n = 10) rats were selected from a population (n = 121) of adult male Wild-type Groningen rats on the basis of their latency time to attack (ALT, s) a male intruder in a resident-intruder test lasting 600 s. In order to obtain information on their cardiac autonomic modulation, ECG recordings were subsequently obtained via radiotelemetry at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HA rats (ALT<90 s) displayed reduced heart rate variability, mostly in terms of lower vagal modulation compared to NA rats (ALT>600 s). Exposure to stressful stimuli (i.e. restraint and psychosocial stress) provoked similar tachycardic responses between the two groups. However, under stress conditions HA rats displayed a reduced vagal antagonism and an increased incidence of tachyarrhythmias compared to NA rats. In addition, beta-adrenergic pharmacological stimulation induced a much larger incidence of ventricular tachyarrhythmias in HA rats compared to NA counterparts. These findings are consistent with the view that high levels of aggressive behavior in rats are associated to signs of cardiac autonomic impairment and increased arrhythmogenic susceptibility that may predict vulnerability to cardiac morbidity and mortality.     

The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis

The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.     

Immediate Effects of Intravenous Verapamil in Cardiac Arrhythmias

Verapamil was administered by intravenous injection to 181 patients with various cardiac arrhythmias. The automaticity of the cardiac pacemaker was slowed in sinus, idionodal, and idioventricular tachycardia. In atrial fibrillation the drug usually slowed the ventricular response and often made it regular. In some cases atrial flutter was converted to sinus rhythm, the ventricular response being reduced in the remainder. Conversion of paroxysmal supraventricular tachycardia to sinus rhythm was consistently achieved. A favourable response occurred in four patients in whom arrhythmias were associated with pre-excitation syndromes. There were no adverse clinical side effects.     

The Morphogenetic Effects of Exogenous Sex Steroid Hormones in the Planarian Girardia tigrina (Turbellaria,Tricladida)

Biophysics - Abstract—Morphogenetic effects of two exogenous sex steroid hormones, testosterone and estradiol, during planarian regeneration have been studied. Anterior regenerants, which...     

Use of Oxprenolol in Cardiac Arrhythmias Associated with Acute Myocardial Ischaemia

Oxprenolol, a new beta-receptor blocking drug with intrinsic sympathomimetic activity, was used to treat 63 episodes of cardiac arrhythmia occurring in 43 patients with acute myocardial infarction or myocardial ischaemia. The drug was most effective in abolishing ventricular ectopic beats and supraventricular tachycardia. The best method of administration was by continuous intravenous infusion and the most satisfactory bolus does was 6 mg. The main side effect was hypotension, which occurred in 59% of episodes of arrhythmia that had responded previously to intravenous administration. Oxprenolol was often effective in lignocaine-resistant arrhythmia. The two main advantages of oxprenolol over propranolol are the reduced likelihood of adversely affecting myocardial function and the diminished tendency to produce bronchospasm.     

Regulation of Oxidative Activity of Neutrophils by Chorionic Gonadotropin: The Role of Female Steroid Sex Hormones

We studied the effect of the main sex hormone, chorionic gonadotropin, on the production of the active forms of oxygen and nitrogen by human neutrophils and the control of its effects by female steroid sex hormones. Gonadotropin proved to inhibit both total production of oxygen metabolites and NO synthesis by the cells. Gonadotropin-dependent regulation of oxidative activity of the neutrophils is controlled by female steroid sex hormones. At the same time, progesterone completely or partially inhibits the suppressive effects of gonadotropin, while estradiol has antagonistic, sensibilizing, or permissive effect on gonadotropin depending on the dose, incubation conditions, and activation status of the cells.     

A Computer Simulation of an Intracellular Mechanism for the Generation and Suppression of Cardiac Arrhythmias

Biophysics - Abstract—This paper reports an analysis of a stochastic model of ion dynamics in the cardiac pacemaker cell within the framework of the generalized two-oscillator...     

Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity,Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats

BackgroundThere is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs).ConclusionOvariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.     

Separation of the Effects of Photoperiod and Hormones on Sex Expression in Cucumber

The effects of photoperiod on the sex expression of cucumberflowers were examined in relation to the endogenous GA and ethyleneproduction with short day (SD)- and long day (LD)-sensitivecultivars under controlled environmental conditions. Growth of plants was greatly reduced under LD in both typesof cultivars. Reflecting this, GA activity was greater and ethyleneevolution less in plants grown under SD than in those underLD. However, the number of pistillate flowers increased underSD and LD in SD- and LD-sensitive cultivar, respectively, indicatingthat a change in sex expression did not coincide with hormonalchanges in the SD-sensitive cultivar. Thus, the effect of photoperiodon the sex expression was found to be separate, at least inpart, from the effect of GA or ethylene in cucumber. (Received September 16, 1982; Accepted December 7, 1982)     

Binding of Steroid Hormones to Histones of Various Origins in Vitro

Kinetin increased the formation of scopoletin and scopolin in tobacco tissue cultures. The formation of scopolin was increased more in the presence of both kinetin (KIN) and l-phenylalanine (Phe) in the medium than in the case of either KIN or Phe alone. The activity of l-phenylalanine ammonia-lyase (PAL) was increased by the addition of KIN. The increase of PAL activity was inhibited by actinomycin-D and cycloheximide added at the same time as the KIN, but actinomycin-D did not inhibit the increase when added at 8 hr after the addition of KIN at which time cycloheximide inhibited it still. The incorporation of [U-¹⁴C]-Phe into scopoletin and scopolin was stimulated by KIN, but its incorporation into protein and lignin was not affected. These results suggest that KIN increased de novo synthesis of PAL through its mRNA, and the enhanced activity of PAL resulted in the increase of scopoletin and scopolin formation.     

Low Energy Defibrillation in Human Cardiac Tissue: A Simulation Study

We aim to assess the effectiveness of feedback-controlled resonant drift pacing as a method for low energy defibrillation. Antitachycardia pacing is the only low energy defibrillation approach to have gained clinical significance, but it is still suboptimal. Low energy defibrillation would avoid adverse side effects associated with high voltage shocks and allow the application of implantable cardioverter defibrillator (ICD) therapy, in cases where such therapy is not tolerated today. We present results of computer simulations of a bidomain model of cardiac tissue with human atrial ionic kinetics. Reentry was initiated and low energy shocks were applied with the same period as the reentry, using feedback to maintain resonance. We demonstrate that such stimulation can move the core of reentrant patterns, in the direction that depends on the location of the electrodes and the time delay in the feedback. Termination of reentry is achieved with shock strength one-order-of-magnitude weaker than in conventional single-shock defibrillation. We conclude that resonant drift pacing can terminate reentry at a fraction of the shock strength currently used for defibrillation and can potentially work where antitachycardia pacing fails, due to the feedback mechanisms. Success depends on a number of details that these numerical simulations have uncovered.     

Cardiac Effects of Magnesium Sulfate Pretreatment on Acute Dichlorvos-Induced Organophosphate Poisoning: An Experimental Study in Rats

Although atropine and oximes are traditionally used in the management of organophosphate poisoning, investigations have been directed to finding additional therapeutic approaches. Thus, the aim of this study was to evaluate the cardiac effects of magnesium sulfate pretreatment on dichlorvos intoxication in rats. Rats were randomly divided into three groups as control, dichlorvos, and magnesium sulfate groups. After 6 h of dichlorvos or corn oil (as a vehicle) injection, venous blood samples were collected, and cardiac tissue samples were obtained. Biochemical analyses were performed to measure some parameters on serum and cardiac tissue. Immunohistochemical analyses of apoptosis and inducible nitric oxide (NO) synthase showed no change in cardiac tissue. Serum cholinesterase levels were markedly depressed with dichlorvos, and further suppressed markedly with magnesium sulfate pretreatment. Although we have demonstrated that serum NO levels in dichlorvos and magnesium sulfate groups were lower than the control group, cardiac tissue NO levels in magnesium sulfate group were higher than the other two groups. Mortality was not significantly affected with magnesium sulfate pretreatment. Uncertainty still persists on the right strategies for the treatment of organophosphate acute poisoning; however, it was concluded that our results do not suggest that magnesium sulfate therapy is beneficial in the management of acute dichlorvos-induced organophosphate poisoning, and also further studies are required.