Human galanin (GAL) and galanin 1 receptor (GALR1) variations are not involved in fat intake and early onset obesity

The neuropeptide galanin (GAL) is involved in food intake and in fat ingestion. Presumably, these effects are conveyed via the galanin 1 receptor (GALR1). We screened the coding region of GAL (including 444 bp of its promoter region) and GALR1 for mutations using single-strand conformation polymorphism analysis and denaturing HPLC in up to 191 obese children and adolescents and 106 healthy underweight young adults (students). In GAL, we identified 3 novel single nucleotide polymorphisms (SNPs; silent: g.-419T-->C, g.-244G-->A; missense: g.47C-->T: Ala16Val) and one infrequent missense variation (c.253A-->G: Asn85Asp), and in GALR1 2 novel SNPs (silent: c.150C-->T, missense: c.793A-->T: Ile265Phe). To test for an association with obesity, we genotyped 7 SNPs (GAL: g.-244G-->A, g.47C-->T, rs7101947, rs1042577, rs3136540; GALR1: c.150C-->T, c.793A-->T) in up to 322 obese children and adolescents compared with up to 277 healthy underweight and normal weight young adults. Furthermore, we analyzed these SNPs with respect to potential effects on the percentage of energy consumed as fat in obese children and adolescents. Allele and genotype frequencies did not differ among the groups tested. In addition, we performed a pedigree transmission disequilibrium test (PDT) for one SNP (GAL: g.-244G-->A) in 610 (518 independent) obesity-trios (obese child or adolescent and both of its parents). However, the PDT for SNP GAL g.-244G-->A revealed no transmission disequilibrium. We conclude that the analyzed SNPs in GAL and GALR1 do not play a major role in early onset obesity or dietary fat intake in the obese children and adolescents of our study groups.     

Loss of Insulin Resistance after Roux-en-Y Gastric Bypass Surgery: a Time Course Study

Background: Gastric bypass has repeatedly been shown to improve and even cure type 2 diabetes by substantially improving insulin resistance. The mechanism by which it achieves this is not currently known, but some have hypothesized that there may be important humoral effects brought about by the bypass of the stomach, duodenum or proximal jejunum. A better understanding of the time course of the changes in insulin resistance after surgery might assist our understanding of potential mechanisms. Methods: Intravenous glucose tolerance tests (IVGTT) were performed in 26 severely obese patients on the morning of gastric bypass surgery and again 6 days later. In addition insulin resistance was assessed in 71 patients undergoing gastric bypass surgery by the homeostasis model assessment (HOMA) method before surgery, and again at 6 days, 3, 6, 9, and 12 months. Patients were divided into 3 groups for analysis: diabetics, impaired glucose tolerance and normal glucose tolerance. Results: All 3 groups of patients were noted to have insulin resistance prior to surgery. This was greatest in the diabetic patients, as indicated by HOMA. There was marked loss of/improvement in insulin resistance within 6 days of gastric bypass by both IVGTT and HOMA methods in all groups, which was maintained over the 12-month period. The study included 31 diabetic patients, of whom only 3 required medication following hospital discharge. Conclusion: The changes in insulin resistance seen after gastric bypass, which are responsible for the resolution or improvement of type 2 diabetes occur within 6 days of the surgery, before any appreciable weight loss has occurred. This finding has implications for our understanding of the mechanism of insulin resistance in severely obese patients and is consistent with a humoral mechanism emanating from the GI tract.     

Participatory action research to understand and reduce health disparities

Participatory action research (PAR) is an excellent way to systematically learn about the conditions under which people experience health disparities, what it is like from the perspective of those experiencing such disparities and, even more importantly, how to ameliorate this major public health problem and create a more equitable and effective health care system. This article describes the method of PAR, supports the appropriateness of PAR to learn about and reduce health disparities, and then presents some specific examples of research projects that have employed or are planning to employ PAR. These examples are from the work of several authors of this article, who are members of an interdisciplinary working group that serves as a forum for discussion of issues related to qualitative research methods and facilitates the development of qualitative studies. All of the authors of this article are part of a task force of this working group that is focusing specifically on community outreach with the goal of reducing health disparities within specific communities.     

Some in vitro and in vivo studies of a new angiotensin I-converting enzyme inhibitor [[S-(R*), S*]-1-[(3-acetylthio)-3-benzoyl-2-methylpropionyl]-L-proline] (CL 242,817) in comparison with captopril

Some in vitro and in vivo properties of CL 242,817, a new angiotensin l-converting enzyme (ACE) inhibitor, were studied and compared to those of captopril. In vitro CL 242,817 effectively inhibited rabbit lung ACE (IC50 54.9 nM), angiotensin l (Al)-induced contractions (IC50 0.82 μM), and potentiated bradykinin (BK)-induced contractions (EC50 0.383μM) of the guinea pig ileum. In these systems, CL 242,817 was approximately 3.5, 27, and 96 times less effective than captopril, respectively. In vivo, equimolar oral doses of CL 242,817 (8.36 mg/kg) and captopril (5 mg/kg) were equieffective in inhibiting the pressor responses to intravenously (i.v.) administered angiotensin l (Al) in normotensive rats and dogs. Similar equimolar oral doses of CL 242,817 and captopril were also equieffective in potentiating the depressor responses to i.v. administered BK in the rat. In the anesthetized dog 30 min after dosing, captopril (0.5 mg/kg i.v.) produced significantly greater potentiation of the BK response than a similar dose of CL 242,817. A single 1 mg/kg i.v. dose of Cl 242,817 or captopril effectively lowered mean arterial blood pressure of the aortic-coarcted hypertensive rat (AHR) and markedly inhibited serum ACE activity after 1 hr. Serum from AHR treated with CL 242,817 or captopril exhibited an apparent loss in ACE inhibition upon cold storage. However, the loss of inhibition of ACE activity was faster with captopril than with CL 242,817. Kinetic studies indicate that CL 242,817 is a pure competive inhibitor of ACE with an estimated Ki of 24.3 nM.     

Sialin, an anion transporter defective in sialic acid storage diseases, shows highly variable expression in adult mouse brain, and is developmentally regulated

Sialin is a lysosomal membrane protein encoded by the SLC17A5 gene, which is mutated in patients with sialic acid storage diseases (SASD). To further understand the role of sialin in normal CNS development and in the progressive neuronal atrophy and dysmyelination seen in SASD, we investigated its normal cellular distribution in adult and developing mice. Overall, sialin showed granular immunoreactivity, consistent with a vesicular protein. Adult mice showed widespread sialin expression, including in the brain, heart, lung, and liver. High-level immunoreactivity was seen in the neuropil of the hippocampus, striatum, and cerebral cortex, as well as in the perikarya of cerebellar Purkinje cells, globus pallidus, and certain thalamic and brainstem nuclei. In mouse embryos, the highest levels of expression were observed in the nervous system. We discuss the possible role of sialin in normal development and in SASD pathogenesis, as a framework for further investigation of its function in these contexts.     

A review of medication administration errors reported in a large psychiatric hospital in the United kingdom

A retrospective analysis of reports of medication administration errors over a period of three and a half years was carried out in a UK psychiatric hospital. A total of 112 errors and "near misses" were studied. The reporting rate increased over time. Psychotropic, intramuscular, and as-needed medications were overrepresented in the error reports. Fifteen percent of the errors had the potential to cause moderate or severe harm to patients. The two most common factors cited by nurses as contributing to error causation were a busy, noisy environment and personal factors, such as feeling tired or unsupported. Physicians were cited as having contributed to some errors.     

The clinical course of acute otitis media in high-risk Australian Aboriginal children: a longitudinal study

Background  

It is unclear why some children with acute otitis media (AOM) have poor outcomes. Our aim was to describe the clinical course of AOM and the associated bacterial nasopharyngeal colonisation in a high-risk population of Australian Aboriginal children.