Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance

Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity

High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance

Urinary Tract Infections in Spinal Cord Injury: Prevention and Treatment Guidelines

Antibiotic therapy is only indicated in symptomatic bacteriuria or in symptomatic exacerbations of chronic UTI. During the acute phase of a SCI, UTI's are more prevalent and bacteria are different and more resistant to antibiotics compared with the chronic phase of SCI. In SCI in general, routine screening urine cultures are not valuable as a high species turn over is seen. Intermittent catheterisation, tapping or Crédé manoeuvre coincide significantly with lower frequency of UTI compared to permanent catheter drainage. No measures are proven efficient in the long term in prevention of bacteriuria or UTI. Methenamine salts are perhaps useful in the prevention of UTI but not in patients with a permanent catheter (level III). Antibiotic prophylaxis was found useful in reducing asymptomatic bacteriuria but not in the prevention of symptomatic infections (level I). However, during prophylaxis a doubling of antibiotic resistance was found. In patients with augmented bladder antibiotic prophylaxis is useless (level II). In chronic SCI the first choice antibiotics are nitrofurantoin or trimethoprim, the second choice are fluoroquinolones (level III) whereas in acute SCI a higher resistance profile to antibiotics is frequent and therefore fluoroquinolones or cefuroxime are suggested (level III). There is no consensus in the literature but we suggest 5 days of antibiotic treatment in UTI during chronic SCI without fever, 7 days in acute SCI without fever and a minimum of 14 days in patients with UTI and fever (level III)