Obesity hypertension: the regulatory role of leptin.

Leptin is a 16-kDa-peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake and elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. While the relevance of endogenous leptin needs further clarification, it appears to function as a pressure and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular, and cardiac damage.

Obesity hypertension: the emerging role of leptin in renal and cardiovascular dyshomeostasis.

PURPOSE OF REVIEW: Adipose tissue is now considered to be an active physiologic system operating in concert with multiple other organs. Leptin is a peptide hormone that is primarily synthesized and secreted by adipose tissue whose principal action is the control of appetite and energy balance. However, current information suggests that leptin exerts pleiotropic effects on several organ systems. Herein, we review the potential role of leptin in cardiovascular and renal physiological conditions as well as pathophysiological situations including obesity and hypertension. RECENT FINDINGS: Increasing evidence suggests that leptin may function as a pressure and volume-regulating factor under conditions of health; however, in situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for adverse renal, vascular and cardiac remodeling. SUMMARY: Adipose tissue should be regarded as a potentially important mediator of cardiorenal physiology. Further research awaits the characterization of additional mechanisms of action of leptin, including its interface with other important endocrine and hemodynamic sodium-volume regulatory systems, in both health and disease, particularly in obesity and related comorbidities. This information could lead to the development of leptin analogues as well as leptin receptor blockers that given specific circumstances could optimize the beneficial actions of the hormone and minimize its deleterious effects.

Cranial computed tomographic findings in a large group of children with drowning: diagnostic, prognostic, and forensic implications.

OBJECTIVES: The primary aim of this study is to better define both the type and incidence of cranial computed tomography (CT) abnormalities in children following submersion injury. DESIGN: This is a retrospective chart review; patients were selected from a drowning registry that extends from January 1989 to April 2006. SETTING: Children's Hospital, San Diego. PATIENTS: Patients were included if they were admitted to the hospital with a diagnosis of drowning and had a cranial CT within 24 hrs of submersion. Of 961 patients in the registry, 156 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighteen percent (28 of 156) of children had an abnormal initial head CT, 82% (128 of 156) had a normal CT. Fifteen percent (24 of 156) of patients initially had a normal head CT and later had an abnormal CT. Abnormal CT findings were remarkable for diffuse loss of gray-white differentiation (75% on presentation) and bilateral basal ganglia edema/infarct (50% on presentation). There was no evidence of intra- or extra-axial blood nor were there any unilateral findings in any of the abnormal CTs. Presenting Glasgow Coma Scale was significantly lower in those who presented with an abnormal versus a normal head CT (p < 0.001). All patients with an abnormal initial CT presented with a Glasgow Coma Scale of 3, and all eventually died. Outcome was also very poor in those with a normal first CT and an abnormal second CT; 54% died and 42% remained in a persistent vegetative state. CONCLUSIONS: These data from the largest study of CT findings in pediatric drowning clearly illustrate that following submersion injury, intra- or extra-axial bleeding is not seen on cranial CT. Furthermore, an abnormal CT scan at any time was associated with a poor outcome (death or persistent vegetative state). The CT findings and the presenting Glasgow Coma Scale of patients with drowning differ from those of patients who have suffered abusive head trauma.

Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease.

The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.

Obesity-hypertension: emerging concepts in pathophysiology and treatment.

The incidence and prevalence of obesity has risen markedly in the last decade, and this epidemic represents a serious health hazard with significant morbidity and mortality. Although hypertension is recognized as one of the most serious consequences of obesity, its pathophysiology remains incompletely understood. Contemporary research suggests that the recently discovered hormone leptin may represent a common link between these 2 pathologic conditions. Leptin is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance. By binding to receptors in the hypothalamus, it reduces food intake and promotes elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. Although the relevance of endogenous leptin needs further clarification for the control of renal sodium excretion and vascular tone, it appears to be a potential pressure and volume-regulating factor in normal situations. However, in conditions of chronic hyperleptinemia, such as obesity, leptin may function pathophysiologically for the development of hypertension as well as cardiac and renal disease. Thus, in addition to weight control, reduction of circulating leptin may confer cardiovascular and renal protective effects in patients with obesity-hypertension.

Leptin as a common link to obesity and hypertension.

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure- and volume-regulating factor, and may function pathophysiologically as a common link to obesity and hypertension.

Leptin as a common link to obesity and hypertension.

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure- and volume-regulating factor, and may function pathophysiologically as a common link to obesity and hypertension.

Detection of traumatic brain injury with magnetic resonance imaging and S-100B protein in children, despite normal computed tomography of the brain.

OBJECTIVE: The objective of this study was to obtain data to further define the extent of traumatic brain injury by using S-100B protein and standard noncontrast magnetic resonance imaging with added fluid-attenuated inversion recovery (FLAIR) and gradient echo sequence in children with normal head computed tomography. DESIGN: Pilot, single cohort, prospective, clinical diagnostic study. SETTING: Pediatric intensive care and intermediate care unit in a tertiary care children's hospital. PATIENTS: Children ages 5-18 yrs who sustained traumatic brain injury, had a negative computed tomography of the brain, and were admitted to hospital were eligible for enrollment. INTERVENTIONS: Two blood samples were drawn for S-100B protein analysis: the first (t-1) as soon as possible or close to 6 hrs of injury and the second (t-2) close to 12 hrs from the time of injury. A magnetic resonance image of the brain was obtained within 96 hrs of injury. MEASUREMENTS AND MAIN RESULTS: Seven of 17 patients (41%) had positive magnetic resonance image. Of the seven patients with positive magnetic resonance image, 100% (seven of seven) had a positive magnetic resonance image with FLAIR sequence, 85% (six of seven) with axial T2 sequence and 50% (three of six) with gradient echo sequence. There was no statistically significant difference in S-100B protein concentrations in patients with a positive magnetic resonance image (n = 7) and those with a negative magnetic resonance image (n = 10; p =.40 at t-1 and p =.13 at t-2). The concentration of S-100B protein was statistically significantly higher in patients with head and other bodily injury (n = 9) compared with isolated head injury (n = 6; p =.018 at t-1 and p =.025 at t-2). Patients with a positive magnetic resonance image had a lower Glasgow Coma Scale score and longer duration of hospital stay. CONCLUSIONS: Magnetic resonance imaging seems to be a useful modality to better define the spectrum of brain injury in children with mild head trauma. The addition of S-100B protein measurement does not seem to be useful in this setting.