New Approaches to Feline Diabetes Mellitus: Glucagon-like peptide-1 analogs.

CLINICAL RELEVANCE: Incretin-based therapies are revolutionizing the field of human diabetes mellitus (DM) by replacing insulin therapy with safer and more convenient long-acting drugs. MECHANISM OF ACTION: Incretin hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) are secreted from the intestinal tract in response to the presence of food in the intestinal lumen. GLP-1 delays gastric emptying and increases satiety. In the pancreas, GLP-1 augments insulin secretion and suppresses glucagon secretion during hyperglycemia in a glucose-dependent manner. It also protects beta cells from oxidative and toxic injury and promotes expansion of beta cell mass. ADVANTAGES: Clinical data have revealed that GLP-1 analog drugs are as effective as insulin in improving glycemic control while reducing body weight in people suffering from type 2 DM. Furthermore, the incidence of hypoglycemia is low with these drugs because of their glucose-dependent mechanism of action. Another significant advantage of these drugs is their duration of action. While insulin injections are administered at least once daily, long-acting GLP-1 analogs have been developed as once-a-week injections and could potentially be administered even less frequently than that in diabetic cats. OUTLINE: This article reviews the physiology of incretin hormones, and the pharmacology and use of GLP-1 analogs, with emphasis on recent research in cats. Further therapies that are based on incretin hormones, such as DPP-4 inhibitors, are also briefly discussed, as are some other treatment modalities that are currently under investigation.

Children's and adolescent's perspectives on cleft lip and/or palate.

OBJECTIVE: Children's voices are being increasingly acknowledged in health care research. The aim of this study was to explore children's and young people's perspectives of being born with a cleft lip and/or palate. DESIGN: The research took a qualitative approach that consisted of two interviews with each child, drawing on child-centered methodologies and techniques. The initial interview focused on children's general life stories, and these often encompassed a discussion about cleft lip and/or palate. The follow-up interview explored specific aspects of the condition and related treatment. PARTICIPANTS: The self-selected sample consisted of 17 children and young people (eight boys, nine girls) with cleft lip and/or palate, aged 8 to 17 years, who received treatment at a dental hospital in the U.K. RESULTS: Children's and young people's accounts identified a number of themes including how they became aware that they had been born with the condition, their views of the treatment pathway, and how it related to who they are. CONCLUSIONS: This study highlights the value of including young people's perspectives in oral health-related research. It has allowed a deeper insight into cleft lip and palate and shows that young people can contribute their views and experiences about services which demonstrate that these could be incorporated into service evaluations.

Caffeine increases the motivation to obtain non-drug reinforcers in rats.

BACKGROUND: Caffeine is widely considered to be a reinforcer in humans, but this effect is difficult to measure in non-human animals. We hypothesized that caffeine may have dual reinforcing effects comparable to nicotine--limited primary reinforcing effects, but potent reinforcement enhancing effects. The present studies tested this hypothesis by investigating the effect of caffeine on responding for non-drug rewards. METHODS: In two experiments, rats were shaped to respond on a progressive ratio (PR) schedule for sucrose solution (20%, w/v; experiment 1) or a fixed ratio 2 (FR2) schedule for a moderately reinforcing visual stimulus (VS; experiment 2). Pretreatment with various doses of caffeine (0-50 mg/kg, intraperitoneal injection) were administered prior to tests over successive week days (M-F). In experiment 1, acute administration of low-moderate caffeine doses (6.25-25 mg/kg) increased responding for sucrose under the PR schedule. This effect of caffeine declined over the initial 15 test days. In experiment 2, only acute pretreatment with 12.5mg/kg caffeine increased responding for the visual stimulus and complete tolerance to this effect of caffeine was observed over the 15 days of testing. In follow up tests we found that abstinence periods of 4 and 8 days resulted in incomplete recovery of the enhancing effects of caffeine. CONCLUSION: The findings suggest that caffeine enhances the reinforcing effects of non-drug stimuli, but that the pharmacological profile of these effects may differ from other psychomotor stimulants.

The role of conditioning history and reinforcer strength in the reinforcement enhancing effects of nicotine in rats.

RATIONALE: Nicotine (NIC) administration can increase behaviors that result in delivery of non-drug reinforcers (e.g., salient sensory stimuli). However, little is known about the circumstances under which NIC increases these behaviors. OBJECTIVE: The present studies sought to extend the reinforcement enhancing effects of NIC to sucrose rewards for which intensity could be systematically manipulated. METHOD: In Experiment 1, rats were trained to respond for sucrose (30% w/v) on a progressive ratio (PR) schedule of reinforcement and were pretreated with NIC (0.4 mg/kg free-base) or physiological saline (SAL). The intensity of the sucrose reward was manipulated over subsequent testing sessions (0-60% w/v). Similar procedures were used in Experiment 2; however, each subject received only one sucrose concentration (0-20%) to control for conditioning history. In Experiment 3, a fixed ratio 3 (FR3) schedule of reinforcement was used to investigate putative activating effects of NIC. Experiment 4 investigated whether NIC pretreatment would reduce sucrose intake in limited-access drinks. RESULTS: In Experiment 1, NIC increased the motivation to obtain all sucrose concentrations, including water. However, when conditioning history was controlled (Experiment 2) the reinforcement enhancing effects of NIC were systematically related to the strength of the reinforcer. In Experiment 3, NIC neither increased nor decreased responding for sucrose. In Experiment 4, NIC reduced sucrose intake, but only at concentrations that resulted in peak drink volumes (5-20%). CONCLUSION: The results suggest that the reinforcement enhancing effects of NIC depend on conditioning history and do not appear to be the result of simple behavioral activation.

Oral health research with children.

BACKGROUND: There has been a shift towards research with children and the adoption of the concept of child-centred research. However, the majority of oral health research is conducted on children, rather than with them. OBJECTIVE: This study aimed to provide an overview of contemporary approaches to research with children. CONSIDERATIONS: The methodological considerations of such research include: the power relationship between the adult researcher and the child participant, with important factors of language use, the setting for the research, appropriate analysis, and quality of the data; ethical factors such as the purpose and risks of the research, confidentiality, recruitment, funding, information to children and parents, consent, and dissemination; and appropriate methods. Methods suitable for oral health research with children include quantitative techniques such as questionnaires and qualitative approaches including interviews individually or in groups and participatory techniques such as time-lines/life grids, drawings, and vignettes. CONCLUSION: There is considerable scope to access children's perspectives of their oral health and care through actively involving them in research. To conduct such research, however, requires training or collaboration with colleagues from other disciplines.