Background Since 2010, more than half of World population lives in Urban Environments. Urban Diab... more Background Since 2010, more than half of World population lives in Urban Environments. Urban Diabetes has arisen as a novel nosological entity in Medicine. Urbanization leads to the accrual of a number of factors increasing the vulnerability to diabetes mellitus and related diseases. Herein we report clinical-epidemiological data of the Milano Metropolitan Area in the contest of the Cities Changing Diabetes Program. Since the epidemiological picture was taken in January 2020, on the edge of COVID-19 outbreak in the Milano Metropolitan Area, a perspective addressing potential interactions between diabetes and obesity prevalence and COVID-19 outbreak, morbidity and mortality will be presented. To counteract lock-down isolation and, in general, social distancing a pilot study was conducted to assess the feasibility and efficacy of tele-monitoring via Flash Glucose control in a cohort of diabetic patients in ASST North Milano. Methods Data presented derive from 1. ISTAT (National Instit...
Over the last few years, new biochemical methodologies have provided direct approaches to extensi... more Over the last few years, new biochemical methodologies have provided direct approaches to extensively investigate central dopaminergic receptors. It has been found that an adenylate cyclase preferentially stimulated by dopamine (DA) is present in several brain dopaminergic areas (16, 20, 35, 37). This finding first allowed a direct pharmacological characterization of compounds with agonist or antagonist properties at the DA receptor level and suggested that physiological responses following interaction between DA and its own receptor are mediated by activation of adenylate cyclase. However, the inhibitory potency of various antipsychotic drugs does not fully correlate with their behavioral and clinical efficacy (33), Moreover, we found that sulpiride and other substituted benzamides, which behave as strong DA antagonists in various animal tests and in clinical applications, fail to inhibit, in contrast to classical neuroleptics, the formation of cyclic AMP elicited by DA or apomorphine both in vitro and in vivo (37, 39, 48). In addition, we observed that some ergot derivatives, endowed with strong DA-mimetic properties in animals and in man, do not stimulate DA-sensitive adenylate cyclase activity in brain homogenates (37, 50). However, we and others have shown that substituted benzamides and dopaminergic ergot derivatives are capable of interacting specifically with central and peripheral DA receptors (15, 37, 39).
Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two ti... more Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2002
Obesity has now been identified as a chronic disease, a global epidemic (globesity) and a serious... more Obesity has now been identified as a chronic disease, a global epidemic (globesity) and a serious public health issue that leads to reduced life expectancy, an increased risk for many serious medical conditions and enormous healthcare costs. The prevalence of obesity and overweight in Italy in 2000 was respectively 9% and 33%, and has grown by 25% over the last five years. Even moderate weight loss can improve obesity-related morbidity and mortality. In November 1997, the US Food and Drug Administration approved sibutramine, a serotonin and noradrenaline reuptake inhibitor, for the treatment of pathological obesity and the management and maintenance of weight loss. In March 2002, sibutramine was temporarily withdrawn from the Italian market on the basis of 47 adverse event reports received between April and December 2001. However, a worldwide review of efficacy and safety data has shown that the overall risk/benefit profile of sibutramine remains favourable, with the rate of fatal reports involving patients receiving sibutramine being 200 times less than the obese women's mortality rate in the Nurses' Health Study. There is strong evidence supporting the usefulness of the correct use of sibutramine in the management of obesity.
PurposeChest x-ray (CXR) severity score and general obesity are predictive risk factors for COVID... more PurposeChest x-ray (CXR) severity score and general obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored.MethodsThis retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19.ResultsPatients with abdominal obesity had significantly higher CXR severity scores and higher rates of these scores than those without abdominal obesity (P<0.001; P=0.001, respectively). While, there were no significant differences between BMI classes (P=0.104; P=0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity score than BMI (r=0.43, P<0.001; r=0.41, P<0.001; r=0.17, P=0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were signi...
Nutrition, Metabolism and Cardiovascular Diseases, 2021
BACKGROUND AND AIMS Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be ... more BACKGROUND AND AIMS Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be a valid alternative to Body Mass Index (BMI) when measuring body fat in adolescents. We aimed to verify whether TMI has better accuracy than BMI in discriminating central obesity and hypertension in adolescents with overweight. METHODS AND RESULTS This monocentric and retrospective cross-sectional study included 3749 pupils, 1889 males and 1860 females, aged 12-13. BMI (kg/m2) was calculated and expressed as percentiles and as z-scores. TMI (kg/m3) was calculated, and we used pre-defined cut-off previously proposed by Peterson et al.. For central obesity we adopted the Waist-to-Height Ratio (WHtR) discriminatory value of 0.5. Hypertension was defined as blood pressure ≥95th percentile of age- sex-, and height-specific references recommended by NHBPEP Working Group. The discriminant ability of TMI, BMI and BMI z-score, with respect to central obesity and hypertension, was investigated using non-parametric receiver operating characteristic analysis. The overall misclassification rate for central obesity was 8.88% for TMI vs 14.10% for BMI percentiles and vs 14.92% for BMI z-scores (P < 0.001). The overall misclassification rate for hypertension was 7.50% for TMI vs 22.03% for BMI percentiles and vs 25.19% for BMI z-scores (P < 0.001). CONCLUSION TMI is a superior body fat index and it could discriminate body fat distribution more accurately than BMI. This supports the use of TMI, in association with WHtR, to characterize adolescents with overweight and high cardio-metabolic risk. Our analysis needs to be extended to other ethnic groups and replicated in a wider age range and in longitudinal studies.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2019
Purpose Adopting a Mediterranean-like dietary pattern may help in preventing several chronic dise... more Purpose Adopting a Mediterranean-like dietary pattern may help in preventing several chronic diseases. We assessed the eating behaviour and compliance with the Mediterranean diet pyramid recommendations in Italy. Methods This is a cross-sectional study conducted in subjects aged ≥ 20 years. A 14-question survey based on the updated Mediterranean diet pyramid was launched online from April 2015 to November 2016. At test completion, a personalized pyramid displaying the possible deficiencies and/or excesses was generated, that could be the basis to plan diet and lifestyle modifications. Results Overall, 27,540 subjects completed the survey: the proportion of females (75.6%), younger subjects (20.7%) and people with a University degree (33.1%) resembled those of the Italian population of Internet users rather than of the general population. 37.8% of participants declared a sedentary lifestyle, including 29.6% of those aged 20–29 years. A lower-than-recommended intake of all food catego...
Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual ... more Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affect...
The present paper describes the effects of different general anaesthetics on plasma catecholamine... more The present paper describes the effects of different general anaesthetics on plasma catecholamine (CA) concentrations taken as biochemical index of peripheral sympathetic activity. In chronically catheterized rats, diethyl ether, ketamine and urethane increased plasma adrenaline (A) and noradrenaline (NA) concentrations, indicating that these drugs stimulate both neurosympathetic and adrenomedullary functions. These effects appear to be centrally mediated, since ganglionic blockade or spinal transection completely counteracted the diethyl ether- and ketamine-induced increases in plasma CA levels. Halothane induced a transient decrease in circulating A and an increase in NA. These results support the concept that general anaesthetics may have different effects on sympathetic function. Arterial blood pressure and heart rate were also measured to look for possible correlations with peripheral sympathetic activity. The enhanced release of peripheral CAs seemed to be the determining factor for increasing blood pressure and heart rate with ketamine only. In the other instances the activation of the peripheral sympathetic system appeared to maintain homeostasis by counterbalancing the various depressive effects of anaesthetics on the cardiovascular system.
Catecholamines: Basic and Clinical Frontiers, 1979
Adrenaline (A), noradrenaline (NA), dopamine (DA), normetanephrine (NM) and p-octopamine (pO) wer... more Adrenaline (A), noradrenaline (NA), dopamine (DA), normetanephrine (NM) and p-octopamine (pO) were measured radioenzymatically in plasma of rats chronically catheterized (vena jugularis) for blood collection. In basal conditions NA is the prevailing circulating amine. Handling, restraint stress and decapitation dramatically increase NA and, even more, A. Halothane and, more markedly urethane anesthesia, increase plasma catecholamines (CA), whereas ganglionic blockade decreases A and NA but not DA. After bilateral adrenalectomy DA remains unchanged, whereas A decreases to undetectable levels. Monoaminooxidase inhibition increases NA, NM, A and pO concentrations in plasma.
Background Since 2010, more than half of World population lives in Urban Environments. Urban Diab... more Background Since 2010, more than half of World population lives in Urban Environments. Urban Diabetes has arisen as a novel nosological entity in Medicine. Urbanization leads to the accrual of a number of factors increasing the vulnerability to diabetes mellitus and related diseases. Herein we report clinical-epidemiological data of the Milano Metropolitan Area in the contest of the Cities Changing Diabetes Program. Since the epidemiological picture was taken in January 2020, on the edge of COVID-19 outbreak in the Milano Metropolitan Area, a perspective addressing potential interactions between diabetes and obesity prevalence and COVID-19 outbreak, morbidity and mortality will be presented. To counteract lock-down isolation and, in general, social distancing a pilot study was conducted to assess the feasibility and efficacy of tele-monitoring via Flash Glucose control in a cohort of diabetic patients in ASST North Milano. Methods Data presented derive from 1. ISTAT (National Instit...
Over the last few years, new biochemical methodologies have provided direct approaches to extensi... more Over the last few years, new biochemical methodologies have provided direct approaches to extensively investigate central dopaminergic receptors. It has been found that an adenylate cyclase preferentially stimulated by dopamine (DA) is present in several brain dopaminergic areas (16, 20, 35, 37). This finding first allowed a direct pharmacological characterization of compounds with agonist or antagonist properties at the DA receptor level and suggested that physiological responses following interaction between DA and its own receptor are mediated by activation of adenylate cyclase. However, the inhibitory potency of various antipsychotic drugs does not fully correlate with their behavioral and clinical efficacy (33), Moreover, we found that sulpiride and other substituted benzamides, which behave as strong DA antagonists in various animal tests and in clinical applications, fail to inhibit, in contrast to classical neuroleptics, the formation of cyclic AMP elicited by DA or apomorphine both in vitro and in vivo (37, 39, 48). In addition, we observed that some ergot derivatives, endowed with strong DA-mimetic properties in animals and in man, do not stimulate DA-sensitive adenylate cyclase activity in brain homogenates (37, 50). However, we and others have shown that substituted benzamides and dopaminergic ergot derivatives are capable of interacting specifically with central and peripheral DA receptors (15, 37, 39).
Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two ti... more Systemic administration of parachlorophenylalanine (PCPA, 100 mg/kg sc on alternate days X two times), a blocker of serotonin (5-HT) synthesis, considerably decreased brain 5-HT and plasma prolactin (PRL) levels in young male rats. Intraventricular (IVT) administration of 5,7-dihydroxytryptamine (5,7-DHT, 200 mug/20 mul), a neurotoxic drug which destroys 5-HT nerve terminals, induced, 3, 12, and 30 days after treatment, a marked depletion of brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and considerably reduced plasma PRL levels at each time interval. Feeding of rat for up to 4 days with a tryptophan (TP)-deficient diet, caused a depletion of brain 5-HT and 5-HIAA contents and did not modify plasma PRL levels. Addition of TP (2 g/kg of diet) to the TP-deficient diet resulted in increased brain 5-HT and 5-HIAA contents and significantly increased PRL levels. These data provide evidence for the role of the 5-HT system in the maintenance of tonic PRL secretion.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2002
Obesity has now been identified as a chronic disease, a global epidemic (globesity) and a serious... more Obesity has now been identified as a chronic disease, a global epidemic (globesity) and a serious public health issue that leads to reduced life expectancy, an increased risk for many serious medical conditions and enormous healthcare costs. The prevalence of obesity and overweight in Italy in 2000 was respectively 9% and 33%, and has grown by 25% over the last five years. Even moderate weight loss can improve obesity-related morbidity and mortality. In November 1997, the US Food and Drug Administration approved sibutramine, a serotonin and noradrenaline reuptake inhibitor, for the treatment of pathological obesity and the management and maintenance of weight loss. In March 2002, sibutramine was temporarily withdrawn from the Italian market on the basis of 47 adverse event reports received between April and December 2001. However, a worldwide review of efficacy and safety data has shown that the overall risk/benefit profile of sibutramine remains favourable, with the rate of fatal reports involving patients receiving sibutramine being 200 times less than the obese women&#39;s mortality rate in the Nurses&#39; Health Study. There is strong evidence supporting the usefulness of the correct use of sibutramine in the management of obesity.
PurposeChest x-ray (CXR) severity score and general obesity are predictive risk factors for COVID... more PurposeChest x-ray (CXR) severity score and general obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored.MethodsThis retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19.ResultsPatients with abdominal obesity had significantly higher CXR severity scores and higher rates of these scores than those without abdominal obesity (P<0.001; P=0.001, respectively). While, there were no significant differences between BMI classes (P=0.104; P=0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity score than BMI (r=0.43, P<0.001; r=0.41, P<0.001; r=0.17, P=0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were signi...
Nutrition, Metabolism and Cardiovascular Diseases, 2021
BACKGROUND AND AIMS Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be ... more BACKGROUND AND AIMS Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be a valid alternative to Body Mass Index (BMI) when measuring body fat in adolescents. We aimed to verify whether TMI has better accuracy than BMI in discriminating central obesity and hypertension in adolescents with overweight. METHODS AND RESULTS This monocentric and retrospective cross-sectional study included 3749 pupils, 1889 males and 1860 females, aged 12-13. BMI (kg/m2) was calculated and expressed as percentiles and as z-scores. TMI (kg/m3) was calculated, and we used pre-defined cut-off previously proposed by Peterson et al.. For central obesity we adopted the Waist-to-Height Ratio (WHtR) discriminatory value of 0.5. Hypertension was defined as blood pressure ≥95th percentile of age- sex-, and height-specific references recommended by NHBPEP Working Group. The discriminant ability of TMI, BMI and BMI z-score, with respect to central obesity and hypertension, was investigated using non-parametric receiver operating characteristic analysis. The overall misclassification rate for central obesity was 8.88% for TMI vs 14.10% for BMI percentiles and vs 14.92% for BMI z-scores (P < 0.001). The overall misclassification rate for hypertension was 7.50% for TMI vs 22.03% for BMI percentiles and vs 25.19% for BMI z-scores (P < 0.001). CONCLUSION TMI is a superior body fat index and it could discriminate body fat distribution more accurately than BMI. This supports the use of TMI, in association with WHtR, to characterize adolescents with overweight and high cardio-metabolic risk. Our analysis needs to be extended to other ethnic groups and replicated in a wider age range and in longitudinal studies.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 2019
Purpose Adopting a Mediterranean-like dietary pattern may help in preventing several chronic dise... more Purpose Adopting a Mediterranean-like dietary pattern may help in preventing several chronic diseases. We assessed the eating behaviour and compliance with the Mediterranean diet pyramid recommendations in Italy. Methods This is a cross-sectional study conducted in subjects aged ≥ 20 years. A 14-question survey based on the updated Mediterranean diet pyramid was launched online from April 2015 to November 2016. At test completion, a personalized pyramid displaying the possible deficiencies and/or excesses was generated, that could be the basis to plan diet and lifestyle modifications. Results Overall, 27,540 subjects completed the survey: the proportion of females (75.6%), younger subjects (20.7%) and people with a University degree (33.1%) resembled those of the Italian population of Internet users rather than of the general population. 37.8% of participants declared a sedentary lifestyle, including 29.6% of those aged 20–29 years. A lower-than-recommended intake of all food catego...
Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual ... more Polycystic ovary syndrome (PCOS) is characterized by hormonal abnormalities that cause menstrual irregularity and reduce ovulation rate and fertility, associated to insulin resistance. Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol, MI) and D-chiro-inositol (cis-1,2,4-trans-3,5,6-cyclohexanehexol, DCI) represent promising treatments for PCOS, having shown some therapeutic benefits without substantial side effects. Because the use of inositols for treating PCOS is widespread, a deep understanding of this treatment option is needed, both in terms of potential mechanisms and efficacy. This review summarizes the current knowledge on the biological effects of MI and DCI and the results obtained from relevant intervention studies with inositols in PCOS. Based on the published results, both MI and DCI represent potential valid therapeutic approaches for the treatment of insulin resistance and its associated metabolic and reproductive disorders, such as those occurring in women affect...
The present paper describes the effects of different general anaesthetics on plasma catecholamine... more The present paper describes the effects of different general anaesthetics on plasma catecholamine (CA) concentrations taken as biochemical index of peripheral sympathetic activity. In chronically catheterized rats, diethyl ether, ketamine and urethane increased plasma adrenaline (A) and noradrenaline (NA) concentrations, indicating that these drugs stimulate both neurosympathetic and adrenomedullary functions. These effects appear to be centrally mediated, since ganglionic blockade or spinal transection completely counteracted the diethyl ether- and ketamine-induced increases in plasma CA levels. Halothane induced a transient decrease in circulating A and an increase in NA. These results support the concept that general anaesthetics may have different effects on sympathetic function. Arterial blood pressure and heart rate were also measured to look for possible correlations with peripheral sympathetic activity. The enhanced release of peripheral CAs seemed to be the determining factor for increasing blood pressure and heart rate with ketamine only. In the other instances the activation of the peripheral sympathetic system appeared to maintain homeostasis by counterbalancing the various depressive effects of anaesthetics on the cardiovascular system.
Catecholamines: Basic and Clinical Frontiers, 1979
Adrenaline (A), noradrenaline (NA), dopamine (DA), normetanephrine (NM) and p-octopamine (pO) wer... more Adrenaline (A), noradrenaline (NA), dopamine (DA), normetanephrine (NM) and p-octopamine (pO) were measured radioenzymatically in plasma of rats chronically catheterized (vena jugularis) for blood collection. In basal conditions NA is the prevailing circulating amine. Handling, restraint stress and decapitation dramatically increase NA and, even more, A. Halothane and, more markedly urethane anesthesia, increase plasma catecholamines (CA), whereas ganglionic blockade decreases A and NA but not DA. After bilateral adrenalectomy DA remains unchanged, whereas A decreases to undetectable levels. Monoaminooxidase inhibition increases NA, NM, A and pO concentrations in plasma.
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Papers by Michele Carruba