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PubMed2002

Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth.

The antidiarrhoeal activity of the seed extract of Albizzia lebbeck (Benth.) was investigated employing conventional rodent models of diarrhoea, i.e. castor oil-induced diarrhoea, upper gastrointestinal transit (u.g.t.) and fluid secretion. It was found that the aqueous methanol extract of Albizzia lebbeck seeds (2.5-5 mg/kg i.p.) possessed antidiarrhoeal activity which strengthens the earlier use of the seeds in the treatment of diarrhoea and dysentery. The antidiarrhoeal dose of the extract was at least 10-30 times less than the LD(50) dose. The extract (2.5-5 mg/kg i.p.) potentiated the antidiarrhoeal activity of loperamide (1 mg/kg i.p.). Nalaxone (0.5 mg/kg i.p.) significantly inhibited the antidiarrhoeal activity of the extract as well as loperamide, thus indicating a role of the opioid system in the antidiarrhoeal activity of the extract.

Animals↗
PubMed2006

Desorption electrospray ionisation mass spectrometry and tandem mass spectrometry of low molecular weight synthetic polymers.

A range of low molecular weight synthetic polymers has been characterised by means of desorption electrospray ionisation (DESI) combined with both mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Accurate mass experiments were used to aid the structural determination of some of the oligomeric materials. The polymers analysed were poly(ethylene glycol) (PEG), polypropylene glycol (PPG), poly(methyl methacrylate) (PMMA) and poly(alpha-methyl styrene). An application of the technique for characterisation of a polymer used as part of an active ingredient in a pharmaceutical tablet is described. The mass spectra and tandem mass spectra of all of the polymers were obtained in seconds, indicating the sensitivity of the technique.

Acetaminophen↗
PubMed1997

Toxicity of cadmium in human trophoblast cells (JAr choriocarcinoma): role of calmodulin and the calmodulin inhibitor, zaldaride maleate.

Cadmium (Cd), the heavy metal, is toxic to the placenta. The objectives of this study were to determine if Cd toxicity is due to inhibition of placental or trophoblast cell proliferation through interactions with the intracellular calcium binding protein, calmodulin (CaM). Cd can replace calcium and thus interfere with CaM's function. Also, CaM inhibitors reverse selected toxic effects of Cd. The CaM inhibitor, zaldaride maleate, was used to determine if Cd inhibits trophoblast cell proliferation through interactions with CaM. JAr choriocarcinoma cells, a neoplastic trophoblast cell line which is similar to early human trophoblast cells, were selected to study this question. Cd (20 and 40 microM) inhibits JAr cell proliferation, as measured by cell number and BrdU incorporation. Zaldaride (10 and 20 microM) inhibits proliferation to a lesser extent; 100 microM is lethal. To determine if zaldaride alters actions of Cd, zaldaride and Cd are added simultaneously. Zaldaride (20 microM) and Cd (20 microM) together inhibit proliferation less than Cd alone, thus partially protecting cells. Metallothionein is induced in cells exposed to Cd, while zaldaride does not cause induction of this cellular defense mechanism protein. To determine if Cd inhibits proliferation through alterations of cell cycle, JAr cells enriched for G0/G1 phase were exposed to 20 microM Cd, 20 microM zaldaride, or 20 microM Cd plus 20 microM zaldaride for 24 hr. Cells remain in G0/G1 following Cd exposure; cells treated with 20 microM zaldaride progress through S phase and into G2. Zaldaride and Cd together allow JAr cells to leave G1 and enter S phase, partially relieving the cycle block produced by Cd. This study demonstrates a role for calmodulin in mediating the toxicity of Cd in trophoblast cell proliferation.

Antidiarrheals↗
PubMed2000

Treatment of Clostridium difficile-associated diarrhea and colitis.

Treatment of C. difficile diarrhea with metronidazole or vancomycin is highly effective at relieving symptoms. The high rate of diarrhea recurrence is concerning, but fortunately most patients respond to a second course of treatment. The problem of vancomycin resistance in hospital organisms has markedly reduced usage of this agent as a first-line treatment for C. difficile diarrhea, leaving metronidazole as the mainstay of treatment in the United States where teicoplanin and fusidic acid are not marketed. It is likely that any new antimicrobial agent used to treat C. difficile will be similarly plagued by a high rate of recurrence, presumably incurred as a result of disruption of normal bowel flora. There is a need for improved treatment and prevention of this increasingly frequent and debilitating nosocomial infection. Treatments that utilize passive antibodies, immunization, nontoxigenic C. difficile, or other forms of biotherapy may hold the key to improved treatment and prevention of C. difficile disease in the future. In the meantime, it behooves all practitioners to use antimicrobials judiciously in order to prevent as many cases of C. difficile diarrhea as possible.

Abdomen, Acute↗
PubMed1993

Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action.

Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) actions of difenoxin and loperamide are mediated by enteric neurones. An iso-osmotic perfusion solution was circulated around the lumen of the jejunum of anaesthetised rats. Vasoactive intestinal peptide was infused intra-arterially to induce net fluid secretion which was inhibited by difenoxin (ED50, 0.23 mg/kg) and loperamide (ED50, 0.5 mg/kg). However, neither were able to restore the fluid transport rate to the control level of absorption. The antisecretory effects of difenoxin (0.77 mg/kg) and loperamide (0.6 mg/kg) were blocked by the opiate receptor antagonist naloxone (2 mg/kg). Their effects were also abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 200 mg/kg; with desmethylimipramine given beforehand to protect noradrenergic nerves and enhance 5-HT depletion). The effect of difenoxin was blocked with methiothepin (1 mg/kg) and methysergide (30 micrograms/kg) but not ketanserin (30 micrograms/kg), ritanserin (30 mg/kg), ondansetron (10 micrograms/kg) or ICS 205-930 (3 mg/kg). None of the above 5-HT receptor antagonists modified the antisecretory effect of loperamide. The antisecretory effect of difenoxin but not loperamide was prevented by phentolamine (2 mg/kg) and by pretreatment with 6-hydroxy-dopamine (150 mg/kg total). It is concluded that both difenoxin and loperamide inhibit net fluid secretion by indirect mechanisms. It is proposed that the initial action is on enteric mu-opiate receptors and that this results in the release of 5-HT. In the case of difenoxin, the 5-HT may act on 5-HT1-like receptors to release noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

A study on oral rehydration therapy of diarrheal disease in western Sicily.

A longitudinal study to ascertain the most common therapeutic approach to diarrheal disease by general practitioners and pediatricians was carried out in Western Sicily. Data obtained showed that of 902 home-managed cases of diarrhea observed by 58 physicians during one year, 65.3% were treated with antibiotics, 8.0% with antimotility agents and 26.7% were not treated with any pharmacological agent (rehydration or diet). Although oral rehydration therapy was widely known by physicians in Western Sicily, only a few of them were willing to use it routinely as the principal and exclusive treatment.

Anti-Bacterial Agents↗
PubMed1990

Effect of antisecretory factor on Escherichia coli STa enterotoxin-induced alkalinisation of pig jejunal acid microclimate.

The effect of challenge by Escherichia coli STa enterotoxin on pig jejunal mucosal surface pH was investigated in vivo. Exposure to STa resulted in a rapid and reversible alkalinisation (P less than 0.001) of the jejunal mucosa from 6.27 +/- 0.11 (5) to 6.89 +/- 0.03 (5). This action of STa is probably mediated through cyclic 3'5'-guanosine monophosphate (cGMP) since the 8-bromo analogue of cGMP induced the same effect as that observed after STa challenge. The action of STa on mucosal pH was partially inhibited by pre-administration of an antisecretory factor (ASF) preparation. The action of 8-bromo cGMP was unchanged by the presence of ASF. This implies that ASF inhibition occurs during the early stages of STa action prior to stimulation of guanylate cyclase. This effect of STa on the pig jejunal mucosal surface pH, or acid microclimate, may explain why weak acid supplementation of oral rehydration solutions can be ineffective in certain types of diarrhoeal disease.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

The effect of antisecretory factor on the permeability of nerve cell membrane to chloride ion.

The antisecretory factor (ASF) is a hormone-like protein (m.w. 60,000) that most effectively counteracts hypersecretion in vivo in the small intestine of pigs and rats. The present report demonstrate that 10(-13) moles of ASF inhibits significantly the 36Cl- permeation through the isolated neuronal plasma membrane of Deiters' cells in rabbits. This effect was enhanced by 0.2 mM gamma-aminobutyric acid (GABA), and quenched by the addition of anti-ASF immunoglobulins; pretreatment of the neuronal membrane with nipecotic acid (10(-6) M) or with bicuculline (10(-3) M) abolished the ASF action whilst picrotoxin (10(-4) M) pretreatment left the inhibitory effect of ASF unaffected. The results suggest that ASF blocks chloride channels in neuronal membranes, including those channels activated by GABA.

Animals↗
PubMed1995

In vitro biological effects of clay minerals advised as substitutes for asbestos.

We studied one sample of commercial sepiolite and two samples of commercial vermiculite--clay minerals proposed as replacements for asbestos--and tested in vitro their abilities to activate complement, to lyse erythrocytes, and to elicit the production of reactive oxygen species (ROS) with human polymorphonuclear leukocytes (PMN) or bovine alveolar macrophages (AM); their behavior was compared with that of asbestos fibers obtained from the Union International Contra Cancer (UICC) as reference standards, as well as with kaolinite and illite, main members of the clay mineral family. Since in short-term in vitro tests the biological activity of mineral particles seems especially related to the active sites on their surface, we first measured the specific surface area of each mineral. Sepiolite was unreactive in two of the three tests we used (complement activation and ROS production) and able to lyse a minimal percentage of red blood cells. Vermiculite was shown to be incapable of activating complement, to have a moderate hemolytic activity and a high ability to elicite ROS production, although lower than that of chrysotile. Sepiolite, therefore, might be of more interest than vermiculite, given the low level of biological effects detected during the tests used to compare both clay minerals with asbestos fibres. The ROS production does not seem to require phagocytosis. A high ROS production was observed with kaolinite: this result casts doubt on the ability of pathogenic mineral dusts in vitro to induce a greater release of ROS than nonpathogenic mineral dusts.

Acridines↗
PubMed1991

Prophylaxis of traveler's diarrhea in Egypt: results of a double blind controlled study.

Diarrhea represents the most frequent health problem of Western tourists visiting subtropical and tropical areas. Antibiotic prophylaxis has been suggested by some authors but may not be generally advisable because of adverse drug effects. In the present study we investigated the prophylaxis of traveler's diarrhea using a combination of tannalbuminate and ethacridin-lactate. During a 16-day cruise in Egypt, 77 tourists were assigned to either placebo or prophylactic doses of tannalbuminate (500 mg) and ethacridin-lactate (50 mg), 1 tbl. b.i.d., in a randomized double-blind fashion. The number of bowel movements, consistency of stools, and clinical symptoms like nausea, abdominal cramps, vomiting, and fever were monitored daily. In the placebo group (n = 43) 35 tourists developed diarrhea (81.4%), whereas in the verum group (n = 34) only 18 tourists (52.9%) had diarrhea (p less than 0.0125). In the travelers receiving verum and developing diarrhea the clinical symptoms were less pronounced than in the placebo group. These results demonstrate that the events of traveler's diarrhea may be reduced; moreover, symptoms are attenuated by medical prophylaxis with tannalbuminate and ethacridin-lactate.

Adult↗
PubMed1981

[New possibilities to improve ileostomy-function by extremely high water-binding substances (author's transl)].

When an ileostoma is performed on rats, they usually die as a result of cachexia, which is caused by poor utilization of ingesta on account of rapid intestinal transit times. Assuming that oral administration of hydrophilic substances would prolong this transit and thereby the time of survival, rats with an ileostoma were fed a newly developed organic monomer. Its capacity to bind water is about 100 times its own weight. This substance was supplemented with standard diet of different concentrations. A much firmer fecal consistency resulted when 33% monomer was added to the diet. Animals fed a diet containing 50% monomer produced well-formed feces. There was no difference in survival time of the animals on a normal diet. furthermore, administration of a special hypercaloric diet did not cause a prolonged survival time. The reasons and possible therapeutic implications for patients with an ileostoma are discussed.

Animals↗
PubMed1989

Long-term functional analysis of the ileoanal reservoir.

Since November 1980, 180 patients underwent abdominal colectomy, rectal mucosectomy, ileoanal reservoir construction, and ileoanal anastomosis at the authors' institutions. One hundred twenty-nine patients had restoration of intestinal continuity before the end of 1986. One hundred fourteen of these patients (88 percent) were available for follow-up at a mean length of time of 5.0 years from ileostomy closure (range, 16 to 88 months). The mean number of pouch evacuations was 5.4 +/- 2.5 during the day (range, 1 to 12) and 1.5 +/- 1.0 at night (range, 0 to 6). Ninety-one percent of patients reported perfect or almost perfect daytime continence, and 74 percent found this true at night. Sixty-three percent of patients believed their pouch function continued to improve over many years. Ninety-five percent of patients questioned would choose an ileoanal reservoir again instead of a permanent ileostomy. This long-term assessment of the function of the ileoanal reservoir confirms that it is a viable, although not perfect, option in the management of ulcerative colitis and familial adenomatous polyposis.

Activities of Daily Living↗
PubMedDate not supplied

Drug therapy of acute diarrhoea in children--actual practice and recommendations.

Forty eight private medical practitioners and fifty six pharmacists were interviewed, using a prepared questionnaire in each group, in an attempt to evaluate the awareness and practice in the treatment of acute diarrhoea in children among private medical practitioners and the role of pharmacists in the dispensing of drugs for diarrhoea in children. 83% of the doctors prescribed an antibacterial agent, 56% prescribed loperamide, 19% of them prescribed diphenoxylate plus atropine while 31% prescribed an absorbent in children for the treatment of acute diarrhoea. Of fifty six pharmacists interviewed, 30 of them sold diphenoxylate on their own and 26 of them honoured a doctor's prescription of the same. 80% of pharmacists interviewed dispensed loperamide, more than 50% of them dispensed an antibacterial agent while 14% dispensed a binding agent such as pectin or kaolin for the treatment of acute diarrhoea without a valid prescription from a doctor. We recommend that the pharmaceuticals prominently display the harmful effects in children of drugs such as the antimotility drugs and immediately withdraw from the market, all pediatric preparations of the same.

Acute Disease↗