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PubMed1994

alpha-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects.

With alpha-glucosidase inhibitors generally improved metabolic control is achieved in NIDDM patients regardless of whether acarbose is administered in addition to other oral anti-diabetic agents or to diet alone. The most significant finding is the reduction of postprandial blood glucose concentrations. Long-term studies show a decrease in glycosylated haemoglobin and often also in fasting blood glucose levels. Placebo-controlled studies have proven that postprandial insulin concentrations are decreased under acarbose treatment while fasting plasma insulin is usually unchanged. The major side-effects of acarbose treatment involve the gastrointestinal system and include flatulence, abdominal discomfort and diarrhoea. Symptoms diminish with treatment time and are less severe when the treatment is started with low doses. Acarbose should usually be initiated as a 50 mg dose immediately before each major carbohydrate containing meal. Monotherapy with acarbose does not cause hypoglycaemia, however, hypoglycaemia may occur with combination of sulphonylurea or insulin treatment by the well-known reasons. In this case hypoglycaemia has to be treated by taking glucose.

Acarbose↗

PubMed2006

Electrical activity in the rectum of anaesthetized dogs.

There is limited data available on the electrical activity of the rectum. An in vivo canine model was developed to record 240 extracellular electrograms simultaneously from the serosal surface of the rectum thereby enabling an off-line reconstruction of the behaviour of the electrical signals. Serosal rectal electrical activity is characterized by brief bursts of action potentials (=spikes) with a frequency of 22 cycles min(-1). High-resolution mapping of these signals revealed predominant propagation of these spikes in the longitudinal direction, originating from any site and conducted for a limited time and length before stopping spontaneously, thereby describing a patch of activity. The dimension of the patches in the longitudinal direction was significantly longer than the transversal width (13.6 vs 2.4 mm; P < 0.001). Spike propagation could occur in the aboral (46% of cases), in the oral (34%) or in both directions (20%). A bolus of betanechol (i.v., 0.5 mg kg(-1)) increased the frequency of the spikes without affecting size, shape or orientation of the patches. As in other parts of the gastrointestinal system, individual spike propagation in the rectum is limited to small areas or patches. The contractile activity of the organ could possibly reflect this underlying pattern of electrical behaviour.

Action Potentials↗

PubMed2006

Constitutive expression of cyclooxygenase-2 in the neuromuscular compartment of normal human colon.

Prostaglandins regulate various functions throughout the gastrointestinal system. Their biosynthesis depends on cyclooxygenase isoforms, named COX-1 and COX-2. The initial hypothesis that COX-2 is an inducible enzyme has been challenged and its constitutive expression in the stomach has been established. In this study, an immunohistochemical analysis was performed to evaluate the distribution and cellular localization of COX-2 in normal human colon. Colonic surgical specimens were processed for COX-2, protein HuC/HuD, neurofilament, S-100 protein and CD117/c-kit immunodetection. COX-2 protein was found to be constitutively expressed in the colonic wall: detectable amounts were localized in mucosal, submucosal and muscular layers, mainly in the neuromuscular compartment. In particular, COX-2 was expressed in muscularis mucosae, submucosal ganglia, longitudinal muscle layer and myenteric ganglia, the neurons of which displayed different degrees of immunostaining. Intramuscular interstitial cells of Cajal, regarded as important sites for the regulation of enteric neuromuscular activity, were also partly COX-2 immunoreactive. This study provides a detailed mapping of COX-2 expression in human colon, and allows better understanding of the roles played by this isoenzyme in gut physiology.

Blotting, Western↗

PubMed1976

Trisomy of chromosome 20.

A neonate with ususual facial features and multiple congenital malformations expired at 4 hours of age. An autopsy revealed severe anomalies of the gastrointestinal system and spinal dysplasia. Cytogenetic evaluation of fibroblasts cultured from a lung biopsy revealed a karyotope of 47,XX,+20.

Abnormalities, Multiple↗

PubMed2004

Survival of dairy cows after surgery to correct abomasal displacement: 1. Clinical and laboratory parameters and overall survival.

The objective of this study was to compare the clinical and laboratory consequences of left and right displacement of the abomasum (LDA and RDA), short- and long-term survival after surgery and the findings in cows, that could not be cured by omentopexy. Data from 564 cases of displaced abomasum (466 LDA, 98 RDA) were analysed retrospectively. Clinical and laboratory findings were compared between the two manifestations of DA. Survival was assessed after 10 days and after 15 months. Necropsy was carried out on cows that died or were killed. On arrival at the clinic, left displacement of the abomasum (LDA) cows had been recognized as diseased for longer. LDA occurred earlier in lactation, and more cows with right displacement of the abomasum (RDA) were pregnant. Overall clinical symptoms were more severe in RDA than in LDA cows. Heart rate was higher, body temperature was lower, inanition, abnormal faeces and ruminal stasis were more frequent in RDA cows. Leucocyte counts were higher, and potassium and chloride levels were lower in RDA cows. Acetonuria was more frequent in LDA cows. More LDA than RDA cows were released from the clinic as cured (82.0% versus 74.5%). However, survival after the early post-surgical period was similar for RDA and LDA cows. At necropsy, diseases of the gastrointestinal system were the predominant finding in RDA cows, while in LDA cows, diseases of the liver and other concurrent diseases were more important.

Abomasum↗

PubMed2004

Canine coronavirus infection in Turkish dog population.

Canine coronavirus (CCoV) is one of the most important viral agents affecting the gastrointestinal system of dogs. In this study virological and serological investigations were performed to demonstrate the existence and prevalence of CCoV infection in a Turkish dog population. A total of 269 animals were subjected to the study. Of 179 dogs tested for CCoV antibodies, 112 (62.5%) were found to be positive by serum neutralization test, while 133 (74.3%) were positive by ELISA. The highest prevalence (94.2%) was detected in kennel dogs. Detection of CCoV genome in faeces was performed in samples from 90 diarrhoeic puppies by reverse transcription-polymerase chain reaction. Fourteen (15.5%) faeces were positive for CCoV RNA, five of which were characterized as CCoV type I. The widespread CCoV infection in the Turkish dog population may be attributed as an important cause of viral diarrhoea in dogs.

Animals↗

PubMed1992

Necrotizing enterocolitis in a perinatal centre.

Thirty-five neonates developed radiologically proven necrotizing enterocolitis (NEC) over a 40 month period. They were 28 +/- 2 weeks gestation, and weighted 1094 +/- 411 g at birth. Eighteen infants (51%) required surgery and three (8.5%) died. The incidence was 6.7% in the very low birthweight (VLBW) infants. A large proportion of NEC (60%) presented beyond 10 days of life. An inverse relationship between gestation and age of onset was observed. The age of presentation was 22 +/- 13 days (range 10-53 days) for the 18 infants less than or equal to 28 weeks compared with 7 +/- 5 days for those over 28 weeks (P less than 0.01). Five NEC infants had bacteraemia which occurred 2-7 days prior to gastrointestinal symptoms of NEC, and four were staphylococcal. Compared with infants controlled for gestation, there was no significant differences observed in perinatal events or feeding history. We concluded that an immature gastrointestinal system is vulnerable to NEC even beyond the early neonatal period.

Enterocolitis, Pseudomembranous↗

PubMed2006

Varied presentations of pseudoxanthoma elasticum in a family.

Pseudoxanthoma elasticum (PXE) is a hereditary disorder of elastic tissue. The characteristic skin changes are asymptomatic yellow papules around the neck and in body folds giving the skin a characteristic cobblestone appearance. The eyes, cardiovascular and gastrointestinal systems are also commonly involved. In this case-series, we present a family of four children, three of whom demonstrated diverse manifestations of PXE. The first child presented with sudden death at age 3 and showed marked coronary and renal arterial intimal fibrosis with prominent fragmentation of the internal elastic lamina, initially attributed to idiopathic arterial calcification. The second child presented with clinical features and histology of the skin typical of PXE at age 11 and the third child, with abnormal, but non-specific cardiological findings at age 8, which raised the possibility of an early stage of PXE. This report emphasizes the importance of considering pseudoxanthoma elasticum in diverse clinical settings, early diagnosis and appropriate screening for asymptomatic family members.

Child↗

PubMed1989

Maternal health, breast-feeding and infant nutrition in Australian aborigines.

Undernutrition is widespread in Australian Aboriginal infants and children and is associated with high rates of infections, particularly of the respiratory and gastrointestinal systems. Maternal ill-health and undernutrition seem to be neglected factors which contribute to the high incidence of low birthweight in Aboriginal babies and to their poor growth in the first five years of life. More effective preventive programmes are needed to help overcome these problems.

Australia↗

PubMed2006

Effect of caffeine on lower esophageal sphincter pressure in Thai healthy volunteers.

Caffeine affects many aspects of body function including the gastrointestinal system. A single-blinded experimental study was performed to evaluate the effect of caffeine on lower esophageal sphincter (LES) and esophageal peristaltic contractions in healthy Thai adults. The volunteers were six men and six women aged 19-31 years. Subjects drank 100 mL of water. Five wet swallows were performed 30 min after the drink. The basal LES pressure was continuously measured using esophageal manometric technique. They then consumed another 100 mL of water containing caffeine at the dose of 3.5 mg/kg body weight. The swallows and basal LES pressure monitoring were repeated. The results showed no change in basal LES pressure after a water drink while caffeine consumption significantly lowered the pressure at 10, 15, 20 and 25 min. The mean amplitude of contractions and peristaltic velocity were decreased at the distal esophagus at 3 and 8 cm above LES. The mean duration of contraction was decreased at the distal part but increased at the more proximal esophagus. The heart rate, systolic and diastolic blood pressures were increased significantly at 10-20 min after caffeine ingestion. This study indicated that caffeine 3.5 mg/kg affected esophageal function, resulting in a decrease in basal LES pressure and distal esophageal contraction, which is known to promote the reflux of gastric contents up into the esophagus.

Adult↗

PubMed2006

Aquaporins contribute to diarrhoea caused by attaching and effacing bacterial pathogens.

Attaching and effacing (A/E) pathogens such as enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) cause serious global health problems. These bacteria colonize the gastrointestinal system, attach to intestinal epithelial cells, efface (collapse) infected cell microvilli and cause overt diarrhoea that may ultimately result in death of the host. Although pathogenically induced diarrhoea is a significant global health issue, the molecular mechanisms that underlie this disease remain largely unknown. A natural murine infection model, employing the A/E pathogen Citrobacter rodentium, has been helpful in studying the diseases in vivo. C. rodentium colonize the colon at high levels, attach to colonocytes, efface microvilli and cause hyperplasia and inflammation in infected mice. As the disease progresses, the mice develop a diarrhoea-like phenotype. Aquaporin (AQP) water channels have been proposed to play a role in the normal dehydration of faecal contents. Here we examine whether C. rodentium infection may alter AQP localization in colonocytes. We demonstrate that during infection, AQP2 and AQP3 are mislocalized from their normal location along cell membranes to the cell cytoplasm. The change in localization of these proteins correlates with the diarrhoea-like phenotype present in infected mice. Mice that recover from the infection at 28-35 days post inoculum regain their normal membrane AQP localization. The altered localization of AQPs is partially dependent on the bacterial type III effector proteins EspF and EspG. We conclude that altered AQP localization may be a contributing factor to diarrhoea during bacterial infection.

Animals↗

PubMed2005

The pitfalls of vaginal construction.

OBJECTIVE: To evaluate a group of young women undergoing complex vaginoplasty, which may be defined as where there has already been previous complex pelvic surgery and the patient is unsuitable for conservative treatment or minor surgical revision. PATIENTS AND METHODS: All patients who had undergone a complex vaginoplasty between 1997 and 2004 were reviewed retrospectively. Information was recorded on the underlying condition, previous surgery and preoperative assessment. The operative technique and complications were noted, and the outcome in terms of menstruation and sexual activity. In all, 15 patients fulfilled the criteria (mean age 22.2 years, range 17-36) and the mean follow-up was 4.75 (0.75-7) years. RESULTS: Fourteen patients had complex congenital anomalies of the lower genital tract and 11 of these had associated anomalies of the urinary and gastrointestinal system; four were XY females. The 15 patients had had 31 vaginal procedures, including ileal vaginoplasty, mobilization of perineal skin flaps and split-skin grafting. Three patients required osteotomies to increase pelvic outlet diameter. The commonest complications were stenosis (six patients) and fistula formation (four). Eight patients are now sexually active; the remaining seven have not attempted sexual intercourse. CONCLUSIONS: Complications are common and can be major; most patients require many repeat operations to achieve a patent vagina. Unfortunately at present, this is the only option for this group of young women to achieve a functional vagina. Patients with complex congenital anomalies of the reproductive and genital tracts are increasingly surviving into adulthood, and the numbers of these patients is likely to increase in the future.

Adolescent↗

PubMed1992

Identification and distribution of 5-HT3 recognition sites in the rat gastrointestinal tract.

1. Tritiated derivatives of the potent and selective 5-HT3 receptor antagonists GR65630 and LY278584 were used to identify 5-HT3 recognition sites in the rat gastrointestinal tract. 2. Binding studies were carried out in homogenates of the rat oesophagus, the cardia, fundus, body and antrum of the stomach, regions of the small intestine, caecum and large intestine. The specific binding of a single concentration of GR65630 (0.5 nM) defined by granisetron (10 microM) in these areas indicated that the density of 5-HT3 recognition sites varied from 2.4 +/- 1.0 to 10.1 +/- 1.0 fmol mg-1 protein. 3. Saturable binding of [3H]-GR65630 could only be demonstrated in the terminal regions of the small intestine (Bmax in the range of 13.83 +/- 4.54-21.19 +/- 0.89 fmol mg-1 protein; mean +/- s.e. mean) and of high affinity (Kd in the range of 0.42 +/- 0.18-0.79 +/- 0.24 nM). Use of [3H]-LY278584 revealed a similar binding density (Bmax 19.54 +/- 0.26 fmol mg-1 protein) and affinity (Kd 1.04 +/- 0.07 nM) in the terminal small intestine. 4. Binding of [3H]-GR65630 and [3H]-LY278584 to the terminal region of the small intestine was inhibited by 5-HT3 receptor ligands ondansetron and S-zacopride (and 5-hydroxytryptamine), but not by 5-HT1, 5-HT2, catecholamine, gamma-aminobutyric acid and opioid receptor ligands. 5. These data demonstrate that there are regional variations in the density of 5-HT3 recognition sites within the rat gastrointestinal tract. Such data are relevant to the potential use of 5-HT3 receptor ligands to modify secretory and contraction responses in the gastrointestinal system.

Affinity Labels↗

PubMed2002

Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease.

Galantamine hydrobromide is a tertiary alkaloid drug that has been developed and approved in a number of countries including the USA and several countries in Europe as a treatment for mild-to-moderate Alzheimer's disease (AD). Galantamine has a unique, dual mode of action. It is a reversible, competitive inhibitor of acetylcholinesterase (AChE), and is the only drug actively marketed for the treatment of AD with proven activity as an allosteric modulator of nicotinic acetylcholine receptors (nAChRs). This latter activity is thought to be particularly important since decreases in the expression and activity of nAChRs make a large contribution to the reduction in central cholinergic neurotransmission in patients with AD. Galantamine exhibits favorable pharmacokinetic characteristics including predictable linear elimination kinetics at the recommended maintenance doses (16 and 24 mg/day), a relatively short half-life (approximately 7 h) and high bioavailability. It is extensively metabolized in numerous pathways, mainly in the liver via cytochrome P450 enzymes CYP2D6 and CYP3A4, and has a low potential for clinically significant drug-drug interactions. During four large randomized, double-blind, placebo-controlled trials of up to 6 months duration, galantamine 16 and 24 mg/day significantly benefited cognitive and global function, ability to perform activities of daily living (ADL) and behavior, relative to placebo and baseline, for up to 6 months. Caregiver burden (time spent by caregivers supervising patients or assisting them with ADL), and caregiver distress (related to patients' behavioral symptoms) were also reduced. Cognitive and functional abilities were preserved at or near baseline for at least 12 months in patients who received galantamine 24 mg/day for 12 months in a long-term US study. These benefits were maximized by early and continued galantamine treatment and, again, were associated with significant reductions in caregiver burden. Trials of the efficacy of galantamine in dementia related to cerebrovascular disease have also yielded positive results. There are no safety concerns associated with the use of galantamine. The incidence of adverse events, particularly cholinergically mediated events affecting the gastrointestinal system, is generally low and can be minimized using the recommended slow dose-escalation scheme. Galantamine may, therefore, help to reduce the overall burden and cost involved in caring for dementia patients. Taking all evidence into account, galantamine has the potential to become a first-line therapy for dementia.

Alzheimer Disease↗

PubMedDate not supplied

Pilot study of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures.

A new anticonvulsant compound, zonisamide (1,2 benzisoxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were higher than plasma concentrations because of red blood cell binding. Steady-state plasma concentrations were higher than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal systems were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day.

Adult↗

PubMed2006

Identification of miltirone as active ingredient of Salvia miltiorrhiza responsible for the reducing effect of root extracts on alcohol intake in rats.

BACKGROUND: Previous work found that extracts from the roots of Salvia miltiorrhiza, a Chinese medicinal herb, reduced alcohol intake in selectively bred Sardinian alcohol-preferring (sP) rats. The present study was designed to evaluate whether miltirone, one of the possible active constituents of S. miltiorrhiza, might be responsible for the reducing effect of the extracts on alcohol intake. METHODS: An initial experiment assessed the effect of 100 mg/kg (intragastric, i.g.) of 4 extracts of S. miltiorrhiza, differing in miltirone content (0, 2, 3, and 7%, respectively), on alcohol intake in alcohol-experienced sP rats exposed to the 2-bottle "alcohol (10%, volume in volume) versus water" choice regimen. Subsequently, the effect of pure miltirone (2.5-10 mg/kg, i.g., i.e., a dose range comparable to its content in the effective doses of the active extracts) on acquisition and maintenance of alcohol-drinking behavior was evaluated in alcohol-naive and alcohol-experienced sP rats exposed to the 2-bottle choice regimen. The effect of miltirone (10 mg/kg, i.g.) on blood alcohol levels was assessed after the i.g. and intraperitoneal (i.p.) administration of alcohol. Finally, the effect of miltirone (30-100 mg/kg, i.g.) on the severity of alcohol withdrawal syndrome was evaluated in Wistar rats made physically dependent on alcohol by the repeated administration of intoxicating doses of alcohol. RESULTS: The reducing effect of 4 different extracts of S. miltiorrhiza on alcohol intake was positively and significantly correlated with their miltirone content. Pure miltirone reduced alcohol intake in alcohol-experienced rats and delayed acquisition of alcohol-drinking behavior in alcohol-naive rats. Similar to S. miltiorrhiza extracts, miltirone markedly reduced blood alcohol levels when alcohol was administered i.g. but not i.p., suggesting that miltirone hampered alcohol absorption from the gastrointestinal system. Finally, miltirone failed to affect the severity of alcohol withdrawal syndrome in alcohol-dependent rats. CONCLUSIONS: The results of the present study suggest that miltirone is the likely active constituent of S. miltiorrhiza responsible for the reducing effect of its extracts on alcohol intake in different experimental models of excessive alcohol consumption.

Alcohol Drinking↗

PubMed1993

Adverse clinical events in dependent long-term nursing home residents.

OBJECTIVE: To assess the occurrence, type, and burden of adverse clinical events (ACE) among residents of chronic facilities. An ACE is any acute or subacute change in health status suggesting acute or subacute illness. DESIGN: Survey with face-to-face functional assessment and 3-month retrospective chart review. STUDY POPULATION: One hundred six continuing-care residents with a minimum length of stay of 4 months at an Italian chronic care facility. MEASUREMENTS: Functional assessment and chart review-based classification of ACE burden on care management according to a clinical-functional Severity Rating Scale. MAIN RESULTS: Functional dependence, dementia and concurrent clinical problems were common. Two hundred seventy-three ACEs were detected. Eighty-nine percent of residents experienced at least one ACE. Only 21% of ACEs could be managed by simple medical intervention and monitoring within 1 day; in 23% there was need for more complex care management; 7% of the latter ACEs resulted in residual (new) functional impairment. Cardiovascular and gastrointestinal systems were most commonly involved in ACEs. Neurological ACEs were the most frequent category leading to new functional impairment (22%). ACE occurrence/burden was higher in male residents (P < 0.01) and strongly associated with the number of concurrent medical problems (P < 0.001). Neither cognitive nor functional dependence levels were related to ACE occurrence. CONCLUSIONS: This description of the burden on care management resulting from acute and subacute changes in clinical and functional status of chronic patients emphasizes the continuing and unpredictable nature of medical attention required in a nursing home or chronic care facility. ACEs occur far more frequently among the elderly than is generally recognized. Thus a high level of medical and nursing skill is necessary in chronic care facilities.

Aged↗

PubMedDate not supplied

Long-term clinical outcome after partial ligation of single extrahepatic vascular anomalies in 20 dogs.

This study reports the long-term clinical outcome after partial ligation of single extrahepatic vascular anomalies in 20 dogs. Outcome was classified as successful or complicated based on review of follow-up evaluations that consisted of telephone contacts with owners and veterinarians (n = 20), in hospital reevaluation (n = 15), and per-rectal portal nuclear scintigraphy (n = 12). Partial ligation was initially effective in resolving clinical signs in all 20 dogs. Long-term outcome was completely satisfactory in 50% of the cases. The mean time interval between surgery and onset of signs, or diagnosis of complications in the 10 dogs with a complicated outcome, was approximately 3 years. Central nervous system, gastrointestinal, and complications related to the urinary tract were most common. Acquired multiple extrahepatic venous communications occurred in at least 3 of 10 dogs (30%) with a complicated outcome. Long-term survival occurred in 13 of 20 dogs (65%) with partial ligation. The mean survival time for the seven dogs that died or were euthanatized was 3.6 years and the mean survival time for the 13 dogs still alive at the last follow-up was 5.0 years.

Animals↗