Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secretin is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. In this report, the organization of the human secretin receptor (hSR) gene was characterized by overlapping genomic phage clones. The hSR gene consists of 13 exons and 12 introns with all the splice donor and acceptor sites conforming to the canonical GT/AG rule. By transient reporter gene assays, the wild-type promoter, containing 3.0 kb of the hSR gene 5' flanking region, was able to drive 5.8 +/- 0.6 and 6.6 +/- 0.2-fold (P < 0.01) increases in luciferase activities in pancreatic ductule-derived PANC-1 and BPD-1 cells, respectively. By subsequent 5' and 3' deletion analysis, a promoter element was identified within -408 to -158, relative to the ATG codon. This promoter element was found to be cell-specific since it could drive reporter gene expression in PANC-1 and BPD-1 cells but not in Hs 262.St, Hs 746T and alphaT3-1 cells. The study of the transcriptional control of human secretin and its receptor should shed light on the pathological developments of pancreatic cancer and autism in the future.
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PMID:The human secretin receptor gene: genomic organization and promoter characterization. 1043 74

The Back to Sleep Campaigns remain the greatest influence on the reduction of sudden infant death syndrome. Blatt and Meguid review updates on the effectiveness of these campaigns in reducing sudden infant death syndrome. They also review studies on why parents do not follow this proven advice. The contribution of the risks of other environmental factors are also reviewed. Also discussed are commentaries from a study reviewed last on the link between a prolonged QT electrocardiogram interval and sudden infant death syndrome. Church provides a cogent and timely review of the reported effectiveness of hormone secretin effectiveness in treating children with autism. This newly proposed treatment has been in the spotlight of the lay public, the popular media, and the scientific community. In short order, secretin as a treatment for autism has moved from a chance observation to the subject of a double-blind, placebo-controlled study.
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PMID:Sudden infant death syndrome and secretin treatment for autism. 1076 70

Recent anecdotal reports have touted the gastrointestinal (GI) hormone secretin as a treatment modality for autism, though there is little clinical evidence or literature to support its viability. We undertook a two-part clinical trial to investigate these claims. Fifty-six patients (49 boys, 7 girls, mean age = 6.4 years, SD = 2.7) enrolled in an open-label trial of secretin, during which they received one injection of the hormone (2 IU/kg). All subjects were evaluated by their parents at baseline and follow-up visits (3-6 weeks later, M = 3.7, SD = 1.4 weeks) with Childhood Autism Rating Scales (CARS). Thirty-four patients were labeled with Pervasive Developmental Disorder Not Otherwise Specified, and 22 met diagnostic criteria for Autistic Disorder. Forty-five patients were concurrently on other drug treatments. At follow-up, some reported minimal but potentially significant improvements including changes in GI symptoms, expressive and/or receptive language function, and improved awareness and social interactions. No adverse effects were reported or observed. Subsequently, 17 of the most responsive patients from Study 1 began a double-blind trial that also included 8 newly enrolled patients. Patients in this second study were alternatively entered into one of two groups and received injections of secretin or placebo with crossover at 4 weeks. Patients from Study 1 entered into Study 2 at an average of 6.5 (SD = 0.8) weeks after beginning Study 1. Results of both inquiries indicate that although treatment with secretin was reported to cause transient changes in speech and behavior in some children, overall it produced few clinically meaningful changes when compared to children given placebo injections.
J Autism Dev Disord 2000 Apr
PMID:Secretin and autism: a two-part clinical investigation. 1145 Aug 25

No medication has yet been shown to consistently alter the symptoms or the course of autism in the majority of patients. The present pharmacotherapy is mainly palliative and sometimes effective in attenuating specific behaviors. The search for better treatment involves examination of the underlying pathophysiology, the genetic or environmental etiology (including possible iatrogenic causes), and assessment of the clinically-generated evidence of efficacy, including serendipitous or unexplained findings. Subtle neuroanatomic and neurochemical changes are being explored and there are anecdotal reports or limited clinical trials that suggest some therapy might be possible. Secretin is a surprising recent addition to the list of candidates. The pharmacologic mechanism by which these agents might provide such effect is not clear, but hypotheses are beginning to emerge. In addition, the prevention of some uncertain number of autism cases is being investigated by examination of certain vaccinations as putative causative or contributory factors. These topics are reviewed in this article, which has the additional purpose of stimulating novel drug discovery efforts for this enigmatic disorder.
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PMID:Is there a basis for novel pharmacotherapy of autism? 1102 52

OBJECTIVE: This study examines the efficacy of intravenous porcine secretin for the treatment of autism. METHODS: Using a randomized, double-blind, placebo-controlled crossover design, 20 subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Schedule-Generic (ADOS-G), and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects. RESULTS: For the primary efficacy analysis, change of ADOS-G social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-1.0 +/- 2.4) and secretin groups (-0.7 +/- 1.4; t 0.34, df 18, P less than.74). No significant differences were obtained for the other measures, including when all 20 subjects were compared by paired t-test from baseline to 4 weeks after secretin infusion. CONCLUSION: There was no evidence for efficacy of secretin in this preliminary randomized controlled trial. These data were collected as part of a multicenter study with the University of California-Irvine and the University of Utah.
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PMID:A Double-Blind, Placebo-Controlled Trial of Secretin for the Treatment of Autistic Disorder. 1110 4

To determine the effect of intravenous porcine secretin on autistic behaviours in children aged 2 to 7 years, the effects of secretin on (1) performance on a standardized language measure, and (2) autistic behaviours, as rated by parents and child development professionals was examined. Employing a randomized, double-blind, placebo-controlled design, 95 participants were assigned to one of two groups and administered a single dose of either secretin or placebo. A follow-up assessment was conducted 3 weeks after the injection. No significant differences in language or autistic behaviour measures were observed at the 3-week follow-up between the groups. Also, there was no significant difference in the proportion of individuals who improved by > or = 6 points on the language measure at follow-up. This study showed no significant effects of secretin on children with autism. Our results are consistent with a systematic review of randomized controlled trials evaluating the effect of secretin in children with autism.
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PMID:Effect of secretin on children with autism: a randomized controlled trial. 1113 52

Autism is a condition characterised by impairments of social communication, social interaction and social imagination. The exact aetiology of autism is unknown but some autistic features have been explained by the 'opioid excess theory' in which excess brain peptide levels have a morphine-like activity. Reduction of peptide levels by administration of the duodenal enzyme Secretin has been found to improve social and language skills in autistic patients. Homeopathic Secretin has been said to produce similar effects. A pilot study was undertaken to study these effects by administration of Secretin to a group of autistic patients. Weekly assessment for 12 weeks was performed by the patients' care workers. Statistical analysis of the mean pre-treatment results compared with the mean treatment results suggested a worsening in the autistic symptoms during treatment. Discussion with the care workers revealed changes and some improvements that were not recordable on the scoring system. Further research into Secretin treatment of autism using a more detailed and customized scoring system would be justified. Following this pilot study a randomised controlled trial of Secretin vs placebo would be appropriate.
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PMID:Homeopathic Secretin in autism: a clinical pilot study. 1134 62

Secretin hormone given daily in transdermal cream was associated with marked and sustained developmental progress in an aphasic two-and-a-half year old child diagnosed with autism.
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PMID:Transdermal secretin for autism - a case report. 1141 75

The paper presents current views concerning childhood autism. The authors present the concepts of etiology of this disorder, emphasizing the role of negative psychical stimuli in early childhood and the role of mother's contact with the child. Organic factors, including genetic background, developmental abnormalities of the nervous system, teratogenic factors and perinatal traumas are also taken into consideration. The role of metabolic factors and enterohormones, particularly those belonging to the secretin group and their effect on the function of the gastrointestinal tract and central nervous system is emphasized. We discuss signs which may be indicative of first symptoms of autism in different age groups. A typical symptom of autism is no development of speech, observed from infancy, taking the form of complete mutism at later stages. It has been emphasized that most pathologic symptoms result from altered perception of external stimuli, which arouse fear and anxiety. Autistic patients may suffer from gastrointestinal tract disturbances such as abdominal pains and diarrhea. Methods used hitherto in the therapy of childhood autism, mainly by psychologists and psychiatrists, as well as some attempts of pharmacological treatment, are presented. The structure and function of secretin, as well as its effects on the motor and secretory function of the stomach and the exocrine function of the pancreas are discussed. The role of secretin in diagnostic tests, among others in the diagnosis of gastrinoma, is emphasized. We also present the history of the application of secretin in the therapy of childhood autism.
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PMID:Use of secretin in the treatment of childhood autism. 1178 69

Secretin, a 27-amino acid neuropeptide, is a member of the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides. The peptide modulates gastrointestinal and neuronal function and is currently being evaluated for the treatment of autism. However, as most peptides, it has a short circulation half-life. Previously, we have shown that VIP self-assembles in aqueous environment and interacts with a biomimetic phospholipid membrane. These in vitro characteristics increase VIP half-life and bioactivity in vivo. The purpose of this study was to investigate whether secretin exhibits similar properties in vitro by forming micelles in aqueous solution and interacting with phospholipids. Results of this study demonstrated that secretin self-assembles to form micelles in HEPES buffer at 25 degrees C above approximately 0.4 microM. Additionally, secretin interacts with a biomimetic phospholipid membrane as indicated from a significant increase in membrane surface pressure (from 25.5 +/- 1.3 to 32.5 +/- 3.0, P < 0.05). Importantly, the peptide undergoes conformational transition from predominantly random coil in saline to alpha-helix in the presence of phospholipid, distearoyl-phosphatidylcholine-poly(ethylene) glycol (mol mass 2000) micelles. We suggest that these distinct biophysical attributes could modulate secretin bioactivity in vivo.
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PMID:Secretin self-assembles and interacts spontaneously with phospholipids in vitro. 1181 35


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