Ghrelin function in human obesity and type 2 diabetes: a concise review.

The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin-mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl-ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction.

Adrenal insufficiency following bariatric surgery.

A 35-year-old woman with morbid obesity and amenorrhoea underwent a bilo-pancreatic diversion (BPD). Surgery was successful with good weight loss, restoration of menstruation and almost immediately she conceived for the first time. She was commenced on routine vitamin supplements after surgery but failed to attend follow-up clinic. Five years later, she presented with limb girdle pains, lethargy, night blindness, skin pigmentation, amenorrhoea and dizziness. She had stopped taking supplements prescribed after the surgery. Investigations showed severe vitamin A and D deficiency along with iron and calcium deficiency. Her cholesterol was low at 3.5 mmol L⁻¹. Despite aggressive vitamin replacement, she continued to complain of lethargy and dizziness. Subsequently, three short adrenocorticotropic hormone-stimulation tests were suboptimal (basal cortisol: 196, 185 and 223 nmol L⁻¹; 30 min cortisol: 421, 453 and 435 nmol L⁻¹). She was subsequently commenced on adrenal replacement and her symptoms resolved and she conceived. We describe for the first time in the literature the unexpected finding of adrenal insufficiency following a BPD.

Safety and efficacy of quinupristin/dalfopristin for treatment of invasive Gram-positive infections in pediatric patients.

BACKGROUND: Antibiotic-resistant Gram-positive pathogens are an increasingly common cause of serious pediatric infections. Although quinupristin/dalfopristin demonstrates favorable activity against resistant Gram-positive pathogens (including many vancomycin-resistant and methicillin-resistant staphylococci), published experience in the pediatric patient population is limited. METHODS: We retrospectively analyzed data from the global quinupristin/dalfopristin Emergency-Use Program, which enrolled patients with serious Gram-positive infections who had no further therapy options because of resistance to, failure on or intolerance to standard antibiotic treatments. Our subset included safety and efficacy data from pediatric patients (age <18 years). There were no restrictions on underlying diseases, severity of illness or prior/concomitant antimicrobial use. RESULTS: Between May 1995 and October 1999, 127 pediatric patients with 131 infections were enrolled. Microbiologic confirmation of etiology was available in 124 patients. All patients had 1 or more concomitant conditions, including malignancy and solid organ or bone marrow transplantation. The most frequent causative pathogens were vancomycin-resistant (80%), spp. (7%), methicillin-resistant (6%) and (4%). All but 21 patients received intravenous quinupristin/dalfopristin 7.5 mg/kg every 8 h. The favorable clinical response rate of quinupristin/dalfopristin was 86 of 124 (69%); the favorable microbiologic response rate was 97 of 124 (78%). Eleven patients (8%) had nonvenous adverse events classified as possibly or probably related to quinupristin/dalfopristin. CONCLUSIONS: Quinupristin/dalfopristin demonstrated favorable response rates and was reasonably well-tolerated in pediatric patients with serious Gram-positive infections unable to receive alternative therapy. In our opinion quinupristin/dalfopristin is a therapeutic option for the management of such infections.

Insulin reduces serum glycosylphosphatidylinositol phospholipase D levels in human type I diabetic patients and streptozotocin diabetic rats.

The enzyme glycosylphosphatidylinositol phospholipase D has a postulated role in the insulin-mimetic signaling pathway of glycosylphosphatidylinositol compounds. We have investigated enzyme activity in the serum of human type I diabetic patients and plasma and tissues of streptozotocin-induced diabetic rats following insulin administration. In the human diabetic patients serum enzyme activity fell by an average of 10.6% (SEM = 2.7; P = 0.008; n = 20) following administration of insulin. In addition serum enzyme activity appeared to be depleted by 27% (SEM = 8.8; P = 0.011; n = 10) compared to nondiabetic controls. In untreated diabetic rats plasma enzyme activity gradually increased 0.3-fold over a 6-week period (P < 0.001; n = 8), this increase was reversed and activity normalized when these animals were treated with insulin. Cloning of the rat glycosylphosphatidylinositol phospholipase D cDNA enabled confirmation of the liver as the principal organ of synthesis. Analysis of mRNA levels in the livers of the diabetic rats showed that gene expression was reduced in the insulin-treated animals compared to the noninsulin-treated controls by 0.7-fold (P = 0.004; n = 4). Tissue enzyme activity was also reduced in the insulin-treated rats; in skeletal muscle enzyme activity was 0.3-fold lower (P = 0.001; n = 4). Insulin therefore decreases glycosylphosphatidylinositol phospholipase D synthesis in diabetic animals resulting in decreased serum enzyme levels, suggesting a relationship between this enzyme and the function of insulin.