Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erec- tion... more Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erec- tion which is adequate for satisfactory sexual in- tercourse. It is a significant male health problem affecting approximately 150 million men world- wide. This value is expected to more than double by the year 2025. The incidence of ED increases sharply with age since it
In the last few years the pathophysi- ological mechanisms of erection have been par- tially clari... more In the last few years the pathophysi- ological mechanisms of erection have been par- tially clarified, and the molecular machinery of the cellular components of the corpus cavernosum (CC) has been widely investigated. Since erection is a vascular event and the penis is a vascular or- gan, there must be an intact endothelium for an erection to occur. The regulation
Journal of biological regulators and homeostatic agents
Hirsutism is the development of androgen-dependent terminal body hair in women in places in which... more Hirsutism is the development of androgen-dependent terminal body hair in women in places in which terminal hair are normally not found. It is often associated with hyperandrogenemia and/or polycystic ovary syndrome (PCOS), but the existence of uncommom hirsutism forms that are not related to altered androgen plasma levels lead also to the definition of - idiopathic hirsutism. Although the pathophysiology of hirsutism has been linked to increasing 5-alpha reductase (SRD5A) activity and to an alteration of the androgen receptor (AR) transcriptional machinery, many aspects remain unclear. In particular, the relationships between androgens and local factors are poorly understood. In the present paper, we selected for a genital skin biopsy, 8 women affected with severe hirsutism (Ferriman-Gallway score greater than 25) but with normal plasma androgen levels, with the exception of slightly higher serum 3alpha-diol-glucuronide levels, and 6 healthy controls and analyzed their androgen- and...
In the era of orally active agents the clinical context of the diagnosis and treatment of erectil... more In the era of orally active agents the clinical context of the diagnosis and treatment of erectile dysfunction (ED) has radically changed. There is a general trend oriented towards choosing invasive diagnostic testing and surgical treatment solutions. Along this view, penile pharmacotesting (PPT) may represent an inexpensive and easy diagnostic procedure to be performed in the office setting. However, this procedure provides no direct vascular imaging, has a high percentage of false diagnoses and its accuracy for subsequent treatment decisions remains quite limited. Hence, home testing with orally active agents may provide better information for the patient's goals. In the diagnostic work-up of ED, the combination of PPT plus colour-duplex Doppler ultrasonography (CDDU) has gained more credit because of a higher diagnostic accuracy than PPT alone, so that it should be always performed when possible. It represents an accurate mean to predict cavernous artery inflow and venous lea...
Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men w... more Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and is associated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, as well as numerous age-related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A rational step-wise approach which includes comprehensive medical and sexual history, a focused physical examination and essential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnostic work-up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penile pharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate only in the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable risk factors or causes, although frequently insufficient to reve...
Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful th... more Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful therapy for male erectile dysfunction (ED) of different aetiology. Recently, sildenafil has been shown to restore erections in temporary ED related to the need of semen collection for assisted reproductive techniques. In this study, we investigated whether sildenafil administration modifies seminal parameters and/or erectile function in normal healthy volunteers. In a double-blind, randomized, placebo-controlled, cross-over two period investigation we enrolled 20 healthy male volunteers (mean +/- SE age 32 +/- 0.5 years). Subjects were not using any medication for the 3 month period prior to the study and were engaged in a stable relationship with proven fertility. The effects of sildenafil (100 mg) on seminal parameters and erectile function after audiovisual sexual stimulation were evaluated by semen analysis and by colour-Duplex ultrasound (the Resistive Index) respectively. In all subj...
We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with e... more We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with erectile dysfunctions (ED). Terminal microcirculation alterations and their correlation with erectile response after drug testing were investigated with power Doppler energy. 134 impotent patients were submitted to CDS during flaccidity: 8 of them (6%) had sparse hyperechoic spots inside the corpora. A standardized intracavernous injection of 10 micrograms alprostadil (PGE1) was followed by audiovisual sexual stimulation. If rigid erection was not achieved after 20 minutes, patients were randomized to redosing of either 10 micrograms PGE1 (phase 2a) or 10 micrograms PGE1 plus 1 mg phentolamine (phase 2b), with reassessment of power Doppler recordings after 20 minutes (peak systolic velocities and the resistive index, RI). A rigid erection (RI > .90) was achieved in 26% of patients after the first injection. As for the remaining patients, the RI was improved in 12% after phase 2a and in...
Excess upper-body (android) fat is considered an health hazard. Exercise training is known to hav... more Excess upper-body (android) fat is considered an health hazard. Exercise training is known to have the potential to modify body composition and to induce a preferential loss of abdominal fat. We studied and compared the composition of whole body and major body regions using dual-energy X-ray absorptiometry (DEXA) in 21 exercising (3-4 hours of intense physical activity/day) and 21 sedentary eumenorrhoic women of similar ages, body mass index (BMI), waist-to-hip ratio (WHR) and age of menarche. In a small number of women in each group (6 out of 21), the ACTH and cortisol response to CRH test and the 24-h urinary cortisol excretion was evaluated. Exercising women had 10% higher total and leg lean mass (p<0.05), and 38% lower total fat mass (p<0.01) than sedentary women. Furthermore, the proportion of android fat was 22% lower in exercising than sedentary women (p<0.01), while the proportion of lower-body (gynoid fat) was unchanged. BMI and WHR were not different between the t...
The understanding of pharmacology of impotence has shown a steady improvement over the last 15 ye... more The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associa...
Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal ti... more Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means of a sensitive HPLC technique, the fasting plasma concentrations of polyamines were measured serially in 11 patients who underwent partial hepatic resection because of focal liver lesions. Samples were obtained before surgery and over the next 6 months, during hepatic regeneration. Liver volume was also measured by ultrasound on the basis of the 3 maximum diameters of the liver. From 2 to 4 weeks after surgery, plasma putrescine increased by a maximum of 78%, and spermidine by approximately 50%. No changes were observed in spermine levels. The spermidine/spermine ratio nearly doubled during liver regeneration. The volume of the liver decrease from 1505 [SD 236] ml to 743 [151] ml after resection, and returned to nearly normal values after 6 months (1231 [100] ml, p &lt; 0.05 vs. basal values). The liver regeneration rate was highest 2-4 weeks after resection, and declined thereafter, when prevailing polyamine concentrations returned to normal. These data show that liver regeneration is accompanied by a significant increase in fasting putrescine and spermidine concentrations, which might be biochemical signals of active liver cell regeneration.
International journal of clinical pharmacology, therapy, and toxicology, 1981
The possibility that the analgesic action of calcitonin could be due to variations in beta-endorp... more The possibility that the analgesic action of calcitonin could be due to variations in beta-endorphin levels in both peripheral blood and cerebrospinal fluid was studied. A total of 40 microgram of synthetic salmon calcitonin was injected i. v. in four male volunteers undergoing minor operations under rachianesthesia. Beta-Endorphin was determined in blood and cerebrospinal fluid samples that were collected before and at regular intervals after calcitonin injection. No statistically significant variation in beta-endorphin levels was observed either in peripheral blood or cerebrospinal fluid. Since the injected calcitonin was free of contaminants (demonstrated by both high pressure liquid chromatography and radioimmunoassay of endorphin made on the injected preparation) and since an increase was observed in the immunoreactive calcitonin in cerebrospinal fluid following calcitonin i. v., self-analgesic action may be hypothesized, even though action through prostaglandins or other syste...
It is known that the same peptide can be identified in different secretory tissues and in the cen... more It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.
The Biochemical Methane Potential (BMP) of winery organic waste, with reference to two Italian re... more The Biochemical Methane Potential (BMP) of winery organic waste, with reference to two Italian red and white grapes (i.e. Nero Buono and Greco) by-products was investigated. The study was carried out to verify the possibility to reduce the production impact in a green-waste-management-chain-perspective. The possibility to efficiently utilize wine-related-by-products for energy production at a micro-scale (i.e. small-medium scale winery production plant) was also verified. Results showed as a good correlation can be established between the percentage of COD removal and the biogas production, as the winery can produce, from its waste methanization, about 7800 kW h year(-1) electrical and 8900 kW h year(-1) thermal. A critical evaluation was performed about the possibility to utilize the proposed approach to realize an optimal biomass waste management and an energetic valorization in a local-energy-production-perspective.
Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erec- tion... more Erectile dysfunction (ED) is defined as the inability to achieve and maintain a penile erec- tion which is adequate for satisfactory sexual in- tercourse. It is a significant male health problem affecting approximately 150 million men world- wide. This value is expected to more than double by the year 2025. The incidence of ED increases sharply with age since it
In the last few years the pathophysi- ological mechanisms of erection have been par- tially clari... more In the last few years the pathophysi- ological mechanisms of erection have been par- tially clarified, and the molecular machinery of the cellular components of the corpus cavernosum (CC) has been widely investigated. Since erection is a vascular event and the penis is a vascular or- gan, there must be an intact endothelium for an erection to occur. The regulation
Journal of biological regulators and homeostatic agents
Hirsutism is the development of androgen-dependent terminal body hair in women in places in which... more Hirsutism is the development of androgen-dependent terminal body hair in women in places in which terminal hair are normally not found. It is often associated with hyperandrogenemia and/or polycystic ovary syndrome (PCOS), but the existence of uncommom hirsutism forms that are not related to altered androgen plasma levels lead also to the definition of - idiopathic hirsutism. Although the pathophysiology of hirsutism has been linked to increasing 5-alpha reductase (SRD5A) activity and to an alteration of the androgen receptor (AR) transcriptional machinery, many aspects remain unclear. In particular, the relationships between androgens and local factors are poorly understood. In the present paper, we selected for a genital skin biopsy, 8 women affected with severe hirsutism (Ferriman-Gallway score greater than 25) but with normal plasma androgen levels, with the exception of slightly higher serum 3alpha-diol-glucuronide levels, and 6 healthy controls and analyzed their androgen- and...
In the era of orally active agents the clinical context of the diagnosis and treatment of erectil... more In the era of orally active agents the clinical context of the diagnosis and treatment of erectile dysfunction (ED) has radically changed. There is a general trend oriented towards choosing invasive diagnostic testing and surgical treatment solutions. Along this view, penile pharmacotesting (PPT) may represent an inexpensive and easy diagnostic procedure to be performed in the office setting. However, this procedure provides no direct vascular imaging, has a high percentage of false diagnoses and its accuracy for subsequent treatment decisions remains quite limited. Hence, home testing with orally active agents may provide better information for the patient's goals. In the diagnostic work-up of ED, the combination of PPT plus colour-duplex Doppler ultrasonography (CDDU) has gained more credit because of a higher diagnostic accuracy than PPT alone, so that it should be always performed when possible. It represents an accurate mean to predict cavernous artery inflow and venous lea...
Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men w... more Erectile dysfunction (ED) is a highly prevalent disorder affecting an estimated 152 million men worldwide and is associated with a variety of behavioral risk factors, such as cigarette smoking and excessive alcohol consumption, as well as numerous age-related medical conditions, notably type-2 diabetes mellitus and cardiovascular disease. A rational step-wise approach which includes comprehensive medical and sexual history, a focused physical examination and essential laboratory tests such as fasting glucose, lipid profile and testosterone assay is to be preferred. Current diagnostic work-up does not recommend any of the specialized tests which were previously considered mandatory-i. e. penile pharmacotesting, Duplex ultrasound and nocturnal penile tumescence. Hormonal replacement therapy is appropriate only in the hypogonadal male with ED. Prior to direct intervention, the physician should consider altering modifiable risk factors or causes, although frequently insufficient to reve...
Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful th... more Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful therapy for male erectile dysfunction (ED) of different aetiology. Recently, sildenafil has been shown to restore erections in temporary ED related to the need of semen collection for assisted reproductive techniques. In this study, we investigated whether sildenafil administration modifies seminal parameters and/or erectile function in normal healthy volunteers. In a double-blind, randomized, placebo-controlled, cross-over two period investigation we enrolled 20 healthy male volunteers (mean +/- SE age 32 +/- 0.5 years). Subjects were not using any medication for the 3 month period prior to the study and were engaged in a stable relationship with proven fertility. The effects of sildenafil (100 mg) on seminal parameters and erectile function after audiovisual sexual stimulation were evaluated by semen analysis and by colour-Duplex ultrasound (the Resistive Index) respectively. In all subj...
We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with e... more We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with erectile dysfunctions (ED). Terminal microcirculation alterations and their correlation with erectile response after drug testing were investigated with power Doppler energy. 134 impotent patients were submitted to CDS during flaccidity: 8 of them (6%) had sparse hyperechoic spots inside the corpora. A standardized intracavernous injection of 10 micrograms alprostadil (PGE1) was followed by audiovisual sexual stimulation. If rigid erection was not achieved after 20 minutes, patients were randomized to redosing of either 10 micrograms PGE1 (phase 2a) or 10 micrograms PGE1 plus 1 mg phentolamine (phase 2b), with reassessment of power Doppler recordings after 20 minutes (peak systolic velocities and the resistive index, RI). A rigid erection (RI > .90) was achieved in 26% of patients after the first injection. As for the remaining patients, the RI was improved in 12% after phase 2a and in...
Excess upper-body (android) fat is considered an health hazard. Exercise training is known to hav... more Excess upper-body (android) fat is considered an health hazard. Exercise training is known to have the potential to modify body composition and to induce a preferential loss of abdominal fat. We studied and compared the composition of whole body and major body regions using dual-energy X-ray absorptiometry (DEXA) in 21 exercising (3-4 hours of intense physical activity/day) and 21 sedentary eumenorrhoic women of similar ages, body mass index (BMI), waist-to-hip ratio (WHR) and age of menarche. In a small number of women in each group (6 out of 21), the ACTH and cortisol response to CRH test and the 24-h urinary cortisol excretion was evaluated. Exercising women had 10% higher total and leg lean mass (p<0.05), and 38% lower total fat mass (p<0.01) than sedentary women. Furthermore, the proportion of android fat was 22% lower in exercising than sedentary women (p<0.01), while the proportion of lower-body (gynoid fat) was unchanged. BMI and WHR were not different between the t...
The understanding of pharmacology of impotence has shown a steady improvement over the last 15 ye... more The understanding of pharmacology of impotence has shown a steady improvement over the last 15 years which has resulted in a better appreciation of the neurovascular mechanisms of the erectile process especially at the level of the corpora cavernosa; however, central mechanisms which control libido and erection are not yet completely elucidated. Frequent diseases most commonly encountered in elderly patients--i.e. diabetes, hypertension, atherosclerosis, depression, etc--represent a frequent cause of erectile dysfunction (ED) and are treated with medications that can interfere with sexual functioning at the central and/or peripheral level. Antidepressants, including the tricyclics and the monoamine oxidase inhibitors, have been implicated in ED, decreased libido, and impaired ejaculation. Most antihypertensives have been associated with some erectile impairment, but diuretics seem to have little effect on erectile function. The calcium channel blockers and ACE inhibitors are associa...
Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal ti... more Polyamines (putrescine, spermidine, and spermine) are widely distributed in animal and vegetal tissues, where their intracellular concentration strictly correlates with normal and pathological cell growth and protein synthesis. By means of a sensitive HPLC technique, the fasting plasma concentrations of polyamines were measured serially in 11 patients who underwent partial hepatic resection because of focal liver lesions. Samples were obtained before surgery and over the next 6 months, during hepatic regeneration. Liver volume was also measured by ultrasound on the basis of the 3 maximum diameters of the liver. From 2 to 4 weeks after surgery, plasma putrescine increased by a maximum of 78%, and spermidine by approximately 50%. No changes were observed in spermine levels. The spermidine/spermine ratio nearly doubled during liver regeneration. The volume of the liver decrease from 1505 [SD 236] ml to 743 [151] ml after resection, and returned to nearly normal values after 6 months (1231 [100] ml, p &lt; 0.05 vs. basal values). The liver regeneration rate was highest 2-4 weeks after resection, and declined thereafter, when prevailing polyamine concentrations returned to normal. These data show that liver regeneration is accompanied by a significant increase in fasting putrescine and spermidine concentrations, which might be biochemical signals of active liver cell regeneration.
International journal of clinical pharmacology, therapy, and toxicology, 1981
The possibility that the analgesic action of calcitonin could be due to variations in beta-endorp... more The possibility that the analgesic action of calcitonin could be due to variations in beta-endorphin levels in both peripheral blood and cerebrospinal fluid was studied. A total of 40 microgram of synthetic salmon calcitonin was injected i. v. in four male volunteers undergoing minor operations under rachianesthesia. Beta-Endorphin was determined in blood and cerebrospinal fluid samples that were collected before and at regular intervals after calcitonin injection. No statistically significant variation in beta-endorphin levels was observed either in peripheral blood or cerebrospinal fluid. Since the injected calcitonin was free of contaminants (demonstrated by both high pressure liquid chromatography and radioimmunoassay of endorphin made on the injected preparation) and since an increase was observed in the immunoreactive calcitonin in cerebrospinal fluid following calcitonin i. v., self-analgesic action may be hypothesized, even though action through prostaglandins or other syste...
It is known that the same peptide can be identified in different secretory tissues and in the cen... more It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.
The Biochemical Methane Potential (BMP) of winery organic waste, with reference to two Italian re... more The Biochemical Methane Potential (BMP) of winery organic waste, with reference to two Italian red and white grapes (i.e. Nero Buono and Greco) by-products was investigated. The study was carried out to verify the possibility to reduce the production impact in a green-waste-management-chain-perspective. The possibility to efficiently utilize wine-related-by-products for energy production at a micro-scale (i.e. small-medium scale winery production plant) was also verified. Results showed as a good correlation can be established between the percentage of COD removal and the biogas production, as the winery can produce, from its waste methanization, about 7800 kW h year(-1) electrical and 8900 kW h year(-1) thermal. A critical evaluation was performed about the possibility to utilize the proposed approach to realize an optimal biomass waste management and an energetic valorization in a local-energy-production-perspective.
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Papers by Andrea Fabbri