Returning to his native Chicago after World War II, Nelson Algren
found a city transformed. The flourishing industry, culture, and
literature that had placed prewar Chicago at center stage in
...American life were entering a time of crisis. The middle class and
economic opportunity were leaving the inner city, and Black
Southerners arriving in Chicago found themselves increasingly
estranged from the nation's economic and cultural resources. For
Algren, Chicago was becoming "an October sort of city even in the
spring," and as Carlo Rotella demonstrates, this metaphorical
landscape of fall led Algren and others to forge a literary form
that traced the American city's transformation. Narratives of
decline, like the complementary narratives of black migration and
inner-city life written by Claude Brown and Gwendolyn Brooks,
became building blocks of the postindustrial urban literature.
October Cities examines these narratives as they played
out in Chicago, Philadelphia, and Manhattan. Through the work of
Algren, Brown, Brooks, and other urban writers, Rotella explores
the relationship of this new literature to the cities it draws upon
for inspiration. The stories told are of neighborhoods and families
molded by dramatic urban transformation on a grand scale with vast
movements of capital and people, racial succession, and an
intensely changing urban landscape.
Obesity Therapy: How and Why? Paccosi, Sara; Cresci, Barbara; Pala, Laura ...
Current medicinal chemistry,
01/2020, Volume:
27, Issue:
2
Journal Article
Peer reviewed
Obesity represents the second preventable mortality cause worldwide, and is very often associated with type 2 Diabetes Mellitus (T2DM). The first line treatment is lifestyle modification to ...weight-loss, but for those who fail to achieve the goal or have difficulty in maintaining achieved results, pharmacological treatment is needed. Few drugs are available today, because of their side effects.
We aim to review actual pharmacological management of obese patients, highlighting differences between Food and Drug Administration - and European Medicine Agency-approved molecules, and pointing out self-medications readily obtainable and widely distributed.
Papers on obesity, weight loss, pharmacotherapy, self- medication and diet-aid products were selected using Medline. Research articles, systematic reviews, clinical trials and meta-analyses were screened.
Anti-obesity drugs with central mechanisms, such as phentermine and lorcaserin, are available in USA, but not in Europe. Phentermine/topiramate and naltrexone/bupropion combinations are now available, even though the former is still under investigation from EMA. Orlistat, with peripheral mechanisms, represents the only drug approved for weight reduction in adolescents. Liraglutide has been approved at higher dose for obesity. Anti-obesity drugs, readily obtainable from the internet, include crude-drug products and supplements for which there is often a lack of compliance to national regulatory standards.
Mechanisms of weight loss drugs include the reduction of energy intake or the increase in energy expenditure and sense of satiety as well as the decrease of hunger or the reduction in calories absorption. Few drugs are approved, and differences exist between USA and Europe. Moreover, herbal medicines and supplements often sold on the internet and widely used by obese patients, present a risk of adverse effects.
•Obesity and insulin resistance role on dendritic cells (DC) function was investigated.•DC from T2DM obese post-menopausal woman express higher mRNA of integrins.•Dendritic cells from T2DM obese ...post-menopausal woman were dysfunctional.•Fetuin and adiponectin in T2DM obese post-menopausal woman were negatively correlated.•Hyperglycaemia significantly impaired CD14 + trans-differentiation into DC.
Cardiovascular disease (CVD) is prevalent in women after menopause, which may be associated with obesity, insulin resistance and metaflammation. Despite the recognized role of immunological mechanisms in vascular remodeling, the role of dendritic cells (DCs) is still unclear. The aim was to characterize monocyte-derived DCs (Mo-DC) in post-menopausal patients with type 2 diabetes (T2DM) and obese woman, without clinical manifestations of atherosclerosis.
Obese post-menopausal women with or without T2DM were enrolled and were compared to age-matched healthy women. DCs obtained from patients were phenotypically and functionally characterized by flow cytometry and mixed lymphocyte reaction. MRNA integrins expression was assessed by real time RT-PCR; circulating fetuin-A and adiponectin levels were measured by ELISA.
Phenotypic dysregulation of Mo-DC reported was related to a defective allogenic lymphocyte stimulation and to an increased mRNA of CD11c, CD18 and DC-SIGN/CD209 which regulate their adhesion to vascular wall cells. Fetuin-A and adiponectin levels were significantly altered and negatively correlated. Hyperglycaemia significantly impaired CD14+ transdifferentiation into Mo-DC.
These data show a dysfunction of Mo-DCs obtained from precursors isolated from T2DM obese post-menopausal woman without any documented clinical CV event. Association of obesity to diabetes seems to worsen DC's phenotype and function and increase vascular inflammation.
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Diabetic Cardiomyopathy (DC) has been defined as a distinct entity characterized by the presence of diastolic or systolic cardiac dysfunction in a diabetic patient in the absence of other causes for ...Cardiomyopathy, such as coronary artery disease (CAD), hypertension (HTN), or valvular heart disease. Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population. Diabetes-related heart disease occurs in the form of coronary artery disease (CAD), cardiac autonomic neuropathy or DC. The prevalence of cardiac failure is high in the diabetic population and DC is a common, but underestimated cause of heart failure in diabetes. The strong association between diabetes and heart failure has fueled intense human and animal research aimed at identifying the mechanisms underlying diabetic myocardial disease. Despite significant progress made, the precise pathogenesis of diabetic Cardiomyopathy is yet to be clearly defined. Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn involved.
We have reviewed the up-to-date scientific literature addressing these issues.
The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DC. In the early stages of the disease, diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction. Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used for early detection of DC. Diabetic patients with microvascular complications show the strongest association between diabetes and Cardiomyopathy, an association that parallels the duration and severity of hyperglycemia.
The management of DC involves improvement in lifestyle, control of glucose and lipid abnormalities, together with treatment of hypertension and CAD, if present.
Patients with diabetes frequently exhibit the combined occurrence of hyperglycemia and dyslipidemia. Published data on their coexistence are often controversial. Some studies provide evidence for ...suboptimal lifestyle and exogenous hyperinsulinism at "mild insulin resistance" in adult diabetic patients as main pathogenic factors. In contrast, other studies confirm that visceral adiposity and insulin resistance are the basic features of dyslipidemia in type 2 diabetes (T2D). The consequence is an excess of free fatty acids, which causes hepatic gluconeogenesis to increase, metabolism in muscles to shift from glucose to lipid, beta-cell lipotoxicity, and an appearance of the classical "lipid triad", without real hypercholesterolemia. Recently, it has been proposed that cholesterol homeostasis is important for an adequate insulin secretory performance of beta-cells. The accumulation of cholesterol in beta-cells, caused by defective high-density lipoprotein (HDL) cholesterol with reduced cholesterol efflux, induces hyperglycemia, impaired insulin secretion, and beta-cell apoptosis. Data from animal models and humans, including humans with Tangier disease, who are characterized by very low HDL cholesterol levels, are frequently associated with hyperglycemia and T2D. Thus, there is a reciprocal influence of dyslipidemia on beta-cell function and inversely of beta-cell dysfunction on lipid metabolism and micro- and macrovascular complications. It remains to be clarified how these different but mutually influencing adverse effects act in together to define measures for a more effective prevention and treatment of micro- and macrovascular complications in diabetes patients. While the control of circulating low-density lipoprotein (LDL) cholesterol and the level of HDL cholesterol are determinant targets for the reduction of cardiovascular risk, based on recent data, these targets should also be considered for the prevention of beta-cell dysfunction and the development of type 2 diabetes. In this review, we analyze consolidated data and recent advances on the relationship between lipid metabolism and diabetes mellitus, with particular attention to the reciprocal effects of the two features of the disease and the development of vascular complications.
Health-related quality of life (HRQL) is poor in obese subjects and is a relevant outcome in intervention studies. We aimed to determine factors associated with poor HRQL in obese patients seeking ...weight loss in medical units, outside specific research projects.
HRQL, together with a number of demographic and clinical parameters, was studied with generic (SF-36, PGWB) and disease-specific (ORWELL-97) questionnaires in an unselected sample of 1,886 (1,494 women; 392 men) obese (BMI > 30 kg/m2) patients aged 20-65 years attending 25 medical units scattered throughout Italy. The clinics provide weight loss treatment using different programs. General psychopathology (SCL-90 questionnaire), the presence of binge eating (Binge Eating scale), previous weight cycling and somatic comorbidity (Charlson's index) were also determined. Scores on SF-36 and PGWB were compared with Italian population norms, and their association with putative determinants of HRQL after adjustment for confounders was assessed through logistic regression analysis.
HRQL scores were significantly lower in women than in men. A greater impairment of quality of life was observed in relation to increasing BMI class, concurrent psychopathology, associated somatic diseases, binge eating, and weight cycling. In multivariate analysis, psychopathology (presence of previously-diagnosed mental disorders and/or elevated scores on SCL-90) was associated with lower HRQL scores on both psychosocial and somatic domains; somatic diseases and higher BMI, after adjustment for confounders, were associated with impairment of physical domains, while binge eating and weight cycling appeared to affect psychosocial domains only.
Psychopathological disturbances are the most relevant factors associated with poor HRQL in obese patients, affecting not only psychosocial, but also physical domains, largely independent of the severity of obesity. Psychological/psychiatric interventions are essential for a comprehensive treatment of obesity, and to improve treatment outcome and to reduce the burden of disease.
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We Who Work the West Kharpertian, Kiara; Rotella, Carlo; Wilson, Christopher P
2020, 2020-06-01
eBook
We Who Work the West examines literary representations of class, labor, and space in the American West from 1885 to 2012. Moving from María Amparo Ruiz de Burton’s representations of ...dispossessed Californio ranchers in the mid-nineteenth century to the urban grid of early twentieth-century San Francisco in Frank Norris’s McTeague to working and unemployed cowboys in the contemporary novels of Cormac McCarthy and Larry McMurtry, Kiara Kharpertian provides a panoramic look at literary renderings of both individual labor—physical, tangible, and often threatened handwork—and the epochal transformations of central institutions of a modernizing West: the farm, the ranchero, the mine, the rodeo, and the Native American reservation. The West that emerges here is both dynamic and diverse, its on-the-ground organization of work, social class, individual mobility, and collective belonging constantly mutating in direct response to historical change and the demands of the natural environment. The literary West thus becomes more than a locus of mythic nostalgia or consumer fantasy about the American past. It becomes a place where the real work of making that West, as well as the suffering and loss it often entailed, is reimagined.  
OBJECTIVE: Recent epidemiological studies suggested that some insulin analogues could be associated with increased risk of cancer. The present study is aimed at assessing the long-term association of ...different insulin analogues with cancer incidence. RESEARCH DESIGN AND METHODS: A nested case-control study dataset was generated from the cohort study dataset (n = 1,340 insulin-treated diabetic outpatients) by sampling control subjects from the risk sets. For each case subject, the control subjects (up to five) were chosen randomly from those members of the cohort who are at risk for the same follow-up time of the case subject. Five-year age classes, sex, and BMI classes (<18.5, 18.5-24.9, 25-29.9, and ≥30 kg/m²) were considered as additional categorical matching variables. RESULTS: During a median follow-up of 75.9 months (interquartile range 27.4-133.7), 112 case subjects of incident cancer were compared with 370 matched control subjects. A significantly higher mean daily dose of glargine was observed in case subjects than in control subjects (0.24 IU/kg/day 0.10-0.39 versus 0.16 IU/kg/day 0.12-0.24, P = 0.036). Incident cancer was associated with a dose of glargine ≥0.3 IU/kg/day even after adjusting for Charlson comorbidity score, other types of insulin administration, and metformin exposure (odds ratio 5.43 95% CI 2.18-13.53, P < 0.001). No association between incident cancer and insulin doses was found for human insulin or other analogues. CONCLUSIONS: The possibility of association between cancer and higher glargine doses suggests that dosages should always be considered when assessing the possible association of insulin and its analogues with cancer.
Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects
Edoardo Mannucci , MD 1 ,
Agostino Ognibene , MD 2 ,
Francesco Cremasco , MD 1 ,
Gianluca ...Bardini , MD 1 ,
Antonella Mencucci , MD 1 ,
Enrica Pierazzuoli , MD 1 ,
Silvia Ciani , BS 1 ,
Gianni Messeri , MS 2 and
Carlo M. Rotella , MD 1
1 Section of Endocrinology, Department of Clinical Pathophysiology, University of Florence
2 Clinical Chemistry Laboratory, Careggi General Hospital, Florence, Italy
Abstract
OBJECTIVE —To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels.
RESEARCH DESIGN AND METHODS —A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin
and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7–36)amide/(7–37) levels were
assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations
of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7–36)amide degradation in human
plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied.
RESULTS —Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin
induced a significant ( P < 0.05) increase of GLP-1(7–36)amide/(7–37) at 30 and 60 min after the oral glucose load (63.8 ± 29.0 vs. 50.3 ± 15.6 pmol/l
and 75.8 ± 35.4 vs. 46.9 ± 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels
were observed in the control group. In pooled human plasma, metformin (0.1–0.5 μg/ml) significantly inhibited degradation
of GLP-1(7–36)amide after a 30-min incubation at 37°C; similar results were obtained in a buffer solution containing DPP-IV.
CONCLUSIONS —Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could
be due to an inhibition of GLP-1 degradation.
ANOVA, analysis of variance
CV, coefficient of variation
DPP-IV, dipeptidyl peptidase IV
GLP-1, glucagon-like peptide 1
Footnotes
Address correspondence and reprint requests to Prof. Carlo M. Rotella, Insegnamento di Malattie Metaboliche e del Ricambio,
Dipartimento di Fisiopatologia Clinica, Viale Pieraccini, 6-50134 Firenze, Italy. E-mail: c.rotella{at}dfc.unifi.it .
Received for publication 13 July 2000 and accepted in revised form 10 November 2000.
C.M.R. is a member of the International Advisory Board on GLP-1 analogs of Novo Nordisk, Denmark. He has received honoraria
from Molteni Farmaceutici, Firenze, and Bayer Farmaceutici, Milan, Italy, which are currently marketing metformin in Italy.
E.M. is a paid consultant for Molteni Farmaceutici.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
Abstract The aim of the study was to assess γ -glutamyl transpeptidase ( γ -GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular ...disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 ± 12.0 months and 39.8 ± 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, γ -GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio 95% confidence interval: 2.54 1.26-5.11, P < .05 and 2.21 0.98-5.43, P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with γ -GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 95% confidence interval, 1.5-28.1), but not diabetes. Elevated γ -GT or AST is an independent predictor of CVD. An increase of γ -GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.
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