Citations

The corpus cavernosum of the penis is one of the few vascular beds in which there is a change in oxygen tension with function (blood PO225-40mm Hg in the flaccid state, and 90-100mm Hg in the erect state). This change in oxygen tension exposes the components of the corpus cavernosum to a variety of cytokines, humoral, vasoactive, and growth factors which may affect the structure and function of the endothelial cells, smooth muscle cells, neurons and extracellular matrix. Among these cell types, endothelial cells are the first line of defense to blood-borne stress and can affect the underlying smooth muscle via paracrine mechanisms. Impotence is defined as the inability to obtain or sustain an erection sufficient for vaginal penetration and can result from a variety of pathological conditions, vascular disease, endocrine disease, neurological disease, and psychogenic disorders. The penis is a vascular organ and as such is susceptible to the effects of vascular diseases. This review will discuss the basic etiology of erection and vasculogenic erectile dysfunction and explore the role oxygen tension in regulating various cellular and humoral factors as well as trabecular structure and function.

The mechanisms mediating the more striking age related increase in cardiovascular disease in women than in men are poorly understood. We tested the hypothesis that aging has a greater impact on sympathetic traffic in women than in men. Muscle sympathetic nerve activity (MSNA), blood pressure, and heart rate were measured in 120 healthy males and 96 healthy females aged 20 to 72 years. MSNA increased with age in both sexes, but age explained 53% of MSNA variance in female subjects and only 8% of MSNA variance in male subjects. Both the slope and intercept of the regression lines were significantly different between male and female groups ( P <0.01 and P <0.001, respectively). For each decade of life, women showed an increase of 6.5 bursts/min in comparison to an increase of 2.6 bursts/min in males. Menopause did not explain the age-related increase in sympathetic traffic. For every 10-burst/min increment in MSNA in subjects older than 40, mean blood pressure increased by 2.7 mm Hg in men and by 6.1 mm Hg in women. Aging is accompanied by a greater increase in sympathetic traffic in women than in men, independent of menopausal status. Sympathetic neural mechanisms may contribute importantly to the more marked influence of age on blood pressure and cardiovascular disease in women.

Medical ultrasound scanners use high-energy pulses to probe the human body. The radiation force resulting from the impact of such pulses on an object can vibrate the object, producing a localized high-intensity sound in the audible range. Here, a theoretical model for the audio sound generated by ultrasound scanners is presented. This model describes the temporal and spectral characteristics of the sound. It has been shown that the sound has rich frequency components at the pulse repetition frequency and its harmonics. Experiments have been conducted in a water tank to measure the sound generated by a clinical ultrasound scanner in various operational modes. Results are in general agreement with the theory. It is shown that a typical ultrasound scanner with a typical spatial-peak pulse-average intensity value at 2 MHz may generate a localized sound-pressure level close to 100 dB relative to 20 μPa in the audible (&lt;20 kHz) range under laboratory conditions. These findings suggest that fetuses may become exposed to a high-intensity audio sound during maternal ultrasound examinations. Therefore, contrary to common beliefs, ultrasound may not be considered a passive tool in fetal imaging.

The basis for ethnicity-related distinctions in gonadotropin secretion are unknown but may have important populational and physiological implications. In male contraceptive trials, exogenous testosterone and progestins suppress spermatogenesis to a greater degree in Asian than Caucasian men. In addition, iv infusion of testosterone inhibits LH release more in Asian than Caucasian volunteers. We test the converse postulate that experimental reduction of androgen-dependent negative feedback by way of the steroidogenic inhibitor combination ketoconazole/dexamethasone will unveil ethnicity-related mechanisms of regulated LH secretion in young men. LH release was monitored by sampling blood every 10 min for 24 h followed by immunoradiometric assay, model-free pulse detection, an entropy (regulatory) statistic, and cosine regression. Statistical comparisons revealed that healthy young Asian and Caucasian men maintain comparable baseline concentrations of LH, testosterone, estradiol, SHBG, and molar testosterone to SHBG ratios. In contrast, the two ethnic groups differ prominently in each of basal, pulsatile, entropic, and 24-h rhythmic LH adaptations to short-term androgen withdrawal. Therefore, we postulate that physiological nonuniformity of sex steroid-dependent negative feedback in particular may contribute to populational diversity in LH regulation.

To evaluate the pathophysiology of altered cortisol secretion in patients with primary adrenal hypercortisolism, cortisol secretion was investigated in 12 patients, seven with a unilateral adenoma and five with ACTH-independent macronodular adrenal hyperplasia compared with age- and gender-matched controls and with patients with pituitary-dependent hypercortisolism. Pulsatile secretion was increased 2-fold (P = 0.04), attributable to increased event frequency (P = 0.002). All patients showed a significant diurnal rhythm with a delay in phase shift of 3 h (P = 0.01). Approximate entropy ratio, a feedback-sensitive measure, was increased compared with controls (P = 0.00003) but similar to that of pituitary-dependent hypercortisolism (P = 0.77), denoting loss of autoregulation. Cortisol burst-mass tended to be smaller in patients with ACTH-independent macronodular adrenal hyperplasia than in unilateral adenoma (P = 0.06). In conclusion, increased cortisol secretion in patients with primary adrenal Cushing’s syndrome is caused by amplified pulsatile secretion via event frequency modulation. We speculate that partial preservation of secretory regularity and diurnal rhythmicity point to incomplete autonomy of these tumors.

Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiploid pathway associated with a high prevalence of IgH translocations and a hyperdiploid pathway associated with multiple trisomies of 8 chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Biallelic dysregulation of CCND1 occurs in nearly 40% of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify 5 recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into 8 TC (translocation/cyclin D) groups (11q13, 6p21, 4p16, maf, D1, D1+D2, D2, and none) that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor.