Iosif Kelesidis

Adiponectin and cancer: a systematic review

Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies, but the mechanisms underlying this relationship remain to be fully elucidated. Adiponectin, an adipocyte secreted endogenous insulin sensitizer, appears to play an important role not only in glucose and lipid metabolism but also in the development and progression of several obesity-related malignancies. In this review, we present recent findings on the association of adiponectin with several malignancies as well as recent data on underlying molecular mechanisms that provide novel insights into the association between obesity and cancer risk. We also identify important research questions that remain unanswered.

Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications

Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

Human infections associated with wild birds

Summary Introduction Wild birds and especially migratory species can become long-distance vectors for a wide range of microorganisms. The objective of the current paper is to summarize available literature on pathogens causing human disease that have been associated with wild bird species. Methods A systematic literature search was performed to identify specific pathogens known to be associated with wild and migratory birds. The evidence for direct transmission of an avian borne pathogen to a human was assessed. Transmission to humans was classified as direct if there is published evidence for such transmission from the avian species to a person or indirect if the transmission requires a vector other than the avian species. Results Several wild and migratory birds serve as reservoirs and/or mechanical vectors (simply carrying a pathogen or dispersing infected arthropod vectors) for numerous infectious agents. An association with transmission from birds to humans was identified for 10 pathogens. Wild birds including migratory species may play a significant role in the epidemiology of influenza A virus, arboviruses such as West Nile virus and enteric bacterial pathogens. Nevertheless only one case of direct transmission from wild birds to humans was found. Conclusion The available evidence suggests wild birds play a limited role in human infectious diseases. Direct transmission of an infectious agent from wild birds to humans is rarely identified. Potential factors and mechanisms involved in the transmission of infectious agents from birds to humans need further elucidation.

Leptin Does Not Mediate Short-Term Fasting-Induced Changes in Growth Hormone Pulsatility but Increases IGF-I in Leptin Deficiency States

CONTEXT States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. OBJECTIVE The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. DESIGN, SETTING, PATIENTS, AND INTERVENTION We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. MAIN OUTCOME MEASURES GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. RESULTS During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. CONCLUSIONS The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

OBJECTIVE Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). DESIGN Hospital-based case-control study. METHODS In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. RESULTS In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH-IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. CONCLUSIONS These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

Giant right atrium with severe pulmonary hypertension

An 84-year-old woman with a history of atrial fibrillation presented with cough, lethargy and symptoms of progressive heart failure. She had not seen a physician for many years, despite persistent symptoms. Physical examination showed an elevated jugular venous pressure, a grade 2/6 holosystolic

Environmental Inputs, Intake of Nutrients, and Endogenous Molecules Contributing to the Regulation of Energy Homeostasis

In the last 20 years the rapid increase in obesity and associated pathologies in developed countries has been accompanied by intensification of research efforts and subsequently a substantial increase in the knowledge of the physiological and molecular mechanisms regulating body mass. These efforts have resulted in the recent discovery of new peripheral hormonal signals as well as new neuropeptides, involved in body-weight homeostasis. This review summarizes new research findings in the area of energy balance regulation, starting from the original classical hypotheses proposing metabolite sensing, through peripheral tissue–brain interactions, and coming full circle to the recently discovered pathways regulating energy homeostasis. Understanding these molecular mechanisms will provide new pharmacological targets for the treatment of obesity and eating disorders and associated comorbidities.

Infections in diabetes mellitus.

Infections constitute the most common cause of diabetic ketoacidosis and uncontrolled diabetes but diabetes also predisposes to the development of serious infections (1,2). The risk of infection and consequent hospitalization is higher in individuals with diabetes than in those without diabetes (3), and some infections, such as rhinocerebral mucormycosis and emphysematous pyelonephritis, occur almost exclusively in patients with diabetes (4). Individuals with diabetes mellitus might be at higher risk of moderate or severe infection-related morbidity and mortality, with almost a double risk of death related to an infection (3). This propensity for infection is attributed to effects of the metabolic dysregulation not only on immune function (5, 6, 7, 8) but also on the nervous and circulatory systems leading to disruption of the natural barriers to infection (9). For example, neuropathic and ischemic ulcers in patients with diabetes provide portals of entry for microorganisms, and neuropathic urinary bladder dysfunction predisposes to urinary tract infections (UTIs) (5,6,9).

Leptin and Its Emerging Role in Children and Adolescents

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent “proof of concept” studies involving leptin administration to humans support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/ caloric deprivation. Moreover, interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. The potential clinical usefulness of leptin in several disease states in children and adolescents, including hypothalamic amenorrhea, eating disorders and syndromes of insulin resistance is still under investigation.

Central Integration of Environmental and Endogenous Signals Important in the Regulation of Food Intake and Energy Expenditure

The worsening global epidemic of obesity has necessitated intensification of research into the mechanisms of appetite regulation. Obesity can be viewed as the result of a classic gene–environment interaction where the human genotype is susceptible to environmental influences that affect energy intake and energy expenditure. The obesity epidemic can also be viewed as a problem of energy balance. Food intake and energy expenditure are processes dependent on information relayed to a central network of sensing and processing neurons through hard-wired neural, metabolic, and hormonal signals from the periphery. Complex pathways that modulate energy balance involve mainly hormonal signals released by the gut and other organs in the periphery that convey information on energy status, as well as appetite centers in the hypothalamus and brain stem. Our understanding of the neuronal pathways that initiate changes in ingestive behavior or energy expenditure as well as our knowledge of the detailed signaling modalities underlying central body weight regulation still remain largely unknown. Careful clarification of how behavioral and environmental factors interact to produce energy balance (and in states of energy excess how the system fails to achieve energy balance, with the end result being weight gain) is required in order to understand the etiology of obesity. Modification of a combination of these factors may be able to reverse the epidemic of obesity and help the population achieve energy balance and a healthy body weight. The purpose of this chapter is to summarize our current understanding of the central pathways regulating energy homeostasis. These neuronal pathways in the central nervous system receive and integrate signals from the periphery that convey information about the status of energy fluxes and stores. Understanding these mechanisms will provide insights for the development of new treatment options for obesity.