[Studies of hemostatic equilibrium in senile and presenile thyropathies in relation to atherosclerotic disease].
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Biomedical subjects
Publications and source records attributed to A Isidori.
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The influence of the administration of ACTH 1-17 on the sexual behavior has been studied in a group of male patients affected by psychogenic impotence, i.e. without any detectable organic reason for such disturbance. The administration of the drug led to a notable increase in the sexual performance of the patients. By the way, all the hormonal parameters taken into account (gonadotropins, sexual steroids, adrenal steroids, etc.), were not affected by the treatment. The AA. conclude therefore that the beneficial effect of the ACTH 1-17 on the sexual behavior was due to a direct action on the CNS and was not hormone-mediated.
Prostaglandin (PG) E and 19-OH PGE, now considered to be the most important of the human seminal prostaglandins, were assayed in infertile and normal men. In the 15 volunteers PGE and 19-OH PGE levels were 23-89 microgram/ml, respectively. In the 4 groups of infertile patients in whom either PGE or 19-OH PGE levels were increased or decreased with respect to normal, sperm concentration and motility were significantly reduced. The negative effects of low levels of seminal prostaglandins on sperm concentration and motility might be correlated respectively with decreased adenylcyclase and testicular androgen activity. The negative effects of high levels of prostaglandins on the seminal fluid might be due either to an inhibition in testicular DNA synthesis or to a decreased sensitivity of the receptors to high titers of prostaglandins.
The case of a 23-year-old man with a pituitary prolactin secreting adenoma is described. With the exception of prolactin all endocrinological parameters were normal. This finding provided an ideal opportunity to assess the role of prolactin on spermatogenesis. Sperm analysis and light microscopy examination of testicular biopsy showed normal spermatogenesis. Electron microscopic studies of the testicular specimen revealed the presence of undivided spermatids, containing two or more nuclei, partially embedded in a developing common acrosome. Morphological studies demonstrated a constant "paired" situation. In most instances two sperms were contained in a single membrane; no single sperm was detected. Following treatment with 5 mg/day bromocriptine prolactin levels decreased and this peculiar abnormality disappeared. In fact, after 2 months of treatment the sperm abnormalities were markedly reduced, whereas no change was found after a period of 120 days. Since this was the only alteration found in the patient with high prolactin levels, a correlation was sought between prolactin levels and cell division. Considering the similarities between prolactin and growth hormone, it might be possible to attribute to prolactin a growth hormone role in the germinal epithelium. This action could be either direct or indirect via an intermediate growth factor.
Recent studies indicate the presence of adenosine binding sites in rat pinealocytes and an effect of their activation on pineal serotonin metabolism. However, controversial data exist, and reports suggest that the role of adenosine in pineal physiology is complex. On this basis, we evaluated the effects of an adenosine analog (N-ethyl-carboxamido-adenosine: NECA) on in vitro and in vivo melatonin production in the rat pineal gland. In the in vitro protocol, pineals were incubated with NECA (0.5 mM, 1 mM, or 2.5 mM) or isoproterenol (ISO: 10(-6)M) for 4 hr. In the in vivo experiments, animals were given NECA (1 mg/kg IP), ISO (0.5 mg/kg IP) or 1 ml saline diluent and sacrificed 2 hr later. The samples were assayed for pineal N-acetyltransferase (NAT) activity and melatonin concentrations. ISO caused the expected marked rise in NAT activity and melatonin levels in both protocols. NECA was ineffective in causing any modification of the parameters measured. We conclude that the adenosine analog NECA may not be involved in the activation of melatonin production. These data contrast with others in which NECA administration resulted in an increase in melatonin levels. The participation, if any, of the purinergic system in the physiology of the pineal gland is still far from being characterized.
Erectile dysfunction is a common (affecting 10-20 million men in the USA) and multifactorial disease due to organic and/or psychological factors that strongly impairs the quality of life in man. During the past decade many advances in the understanding of the pathophysiology of erectile dysfunction have been made and new therapeutic strategies have become available. It has been established that an insufficient production of nitric oxide by penile nerve terminals and/or vascular endothelium may result in an impaired erection or complete impotence. Nowadays, intracavernous injection of vasoactive drugs represents a standardized approach for the diagnosis, and the treatment of choice, for erectile dysfunction, but is not widely accepted by the patients. The possibility of treating erectile dysfunction with intraurethral administration of prostaglandin-E1 has recently become available in the USA, and is a therapy more acceptable to the patients. Other noninvasive medical therapies are undergoing evaluation.
A critical review of the gonadotropin therapy in male infertility or hypofertility is presented. In the author's opinion, the poor and conflicting results so far obtained wih this kind of treatment are mainly due to inadequate selection of the patients admitted to the treatment itself. The author stresses some points concerning the modern knowledge on the physiology of gonadotropin secretion in males; points that must be borne in mind in approaching this type of treatment, and which in some way revolutionize the old concept of "low" or "high" plasma gonadotropin levels. In this concern, the gonadotropin therapy can be applied not only to the hypogonadotropic hypogonadism, as for the past, but also to the spermatogenic arrests and to the idiopathic oligospermiogenesis wtih "normal" gonadotropin levels. The author then exposes the rigid criteria adopted in the Andrologic Center of the 5th Medical Clinic of the University of Rome for the selection of the patients to be admitted to the treatment; criteria which are based on hormonal, morphological and seminal parameters. In the final part the results are reported obtained in the selected patients with a treatment schedule with associated HMG + MCG (150--300 I.U. as FSH per week and 2000--6000 I.U. as LH per week for 12--16 weeks). The results seem very encouraging: in 85% of the patients a quantitative and qualitative amelioration of the spermatogenesis was obtained; in 30% of these cases an outcome of pregnancies in the partner has been documented so far.
Erectile dysfunction (ED) is the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. The disorder is age-associated, with estimated prevalence rates of 39% among men 40 years old and 67% among those 70 years old. ED is a common (2 to 3 million males in Italy) and multifactorial disease due to organic and/or psychological factors that strongly impair the quality of life in man. During the last decade many advances in the understanding of the pathophysiology of ED have been made and new therapeutic strategies have become available. It has been established that an insufficient production of nitric oxide by penile nerve terminals and/or vascular endothelium may result in an impaired erection or complete impotence. Nowadays, intracavernous injection of vasoactive drugs represents a standardised approach for the diagnosis and a treatment option for ED, but is not widely accepted by the patients. The possibility of treating ED with new oral agents (i.e. sildenafil, apomorphine, phentolamine) or intraurethral administration of prostaglandin-E1 made this therapy more acceptable. Vacuum erection devices and penile prostheses represent second-line treatments. Men with ED caused by endocrine disorders (i.e. hypogonadism, prolactinomas) should be treated appropriately (i.e. testosterone and dopaminergic agonists, respectively). Amongst new drugs, sildenafil is considered the most promising: it is a potent inhibitor of type-5 phosphodiesterase in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Oral sildenafil (25-100 mg when needed) is an effective and well-tolerated treatment in impotent men suffering from ED of unknown etiology.
It was proposed that lipocalin type prostaglandin D synthase (L-PGD-S), a bifunctional protein both synthesizing PGD2 and transporting retinoids and other lipophilic ligands, could be involved in the development and the maturation of sperm. In the present study, the seminal plasma (SP) of 59 adult males was analyzed by standard WHO methods and immunoblotting, using a monospecific polyclonal antibody directed against L-PGD-S. Briefly, aliquots of SP (2.5 microl), were fractionated by polyacrylamide electrophoresis in the presence of sodium dodecyl sulfate, the blots were stained and densitometrically analyzed. To obtain quantitative data, the aliquot of SP was selected within the linear part of the dose/band intensity curve and a proper quality control was analyzed in all blots to normalize the intensity of the bands of different experiments. A significant reduction (p<0.05) of the L-PGD-S levels was observed in severe oligozoospermic patients compared to normozoospermic subjects and a significant correlation between L-PGD-S levels and sperm concentration was found, as reported by other authors. Further studies are warranted to evaluate the possible diagnostic and pharmacological applications of these observations.
Secretory patterns of some anterior pituitary hormones were recorded during sleep, and related to EEG-phases. The same observations were carried out in conditions in which the normal sleep course was intentionall (i.e., repeated arousals, administration of tryptophan) or pathologically (i.e. chronic schizophrenia) modified. Plasma gonadotropins (lh, fsh), growth hormone and ACTH were assayed. In basal conditions, the well-known peak of HGH, which corresponds to the delta phase of sleep, was confirmed. This peak is strictly linked to the number and duration of stage 4 sleep, and follows it in its experimental and/or pathological disturbances. The secretion of ACTH, on the other hand, seems to be completely independent from the morphology of sleep. The secretion of this hormone is typically phasic; along with this phasic secretion, a background secretion is detectable, which increases steadily during the sleep span, with maximal values in the early morning hours. Gonadotropin secretion is pulsatile, episodic and completely independent from the sleep phases, in basal as well as in experimental and pathologic conditions.
Awareness of the complex relation linking reproductive function and other major organ systems has been increasing only recently. We have tried to delineate some recent advances in our knowledge of male reproductive function and its disorders as they relate to Internal Medicine. The regulation of Gn-RH secretion and the influence of Gn-RH on gonadotropin secretion are among the most interesting aspects of hypothalamic-pituitary function. The pulsatile pattern of LH secretion is of particular interest in relation to the influence of gonadotropin secretory pattern on testis response. In this regard oligozoospermia with elevated FSH levels and decreased frequency of LH pulses has been identified. Sertoli cells play an essential role in the control of spermatogenesis. We investigated some features of human Sertoli cell function in vitro. These cells secrete transferrin and ABP, and hABP has an affinity for DHT which is different from that of liver-produced SHBG. Seminal transferrin is closely linked to spermatogenesis in oligozoospermia as well as in azoospermia due to damaged spermatogenesis. As a third point of interest paracrine control of testis function, and especially the paracrine role of endogenous opiates and several growth factors are described. LH pulsatility was studied in several medical and endocrine disorders to investigate their impact on male reproductive function. An altered pattern of LH secretion was found in most of the diseases investigated, and in some instances there were hints of hypothalamic involvement. Finally the negative influence on male reproductive function of several drugs, commonly used in the practice of internal medicine is stressed.
The present paper reports our personal data on gonadotropin therapy in patients with idiopathic secretory oligozoospermia due to a low biological activity of LH. In recent years the use of more specific diagnostic procedures, particularly the biological assay of gonadotropins, and a better knowledge of the biological and pharmacological properties of hormones, increased the indications of hormonal treatment in male infertility, not only through the synthesis of new active compounds but mainly broading the field of application of gonadotropins.