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Effectiveness of devices purported to reduce flatus odor.

OBJECTIVE: A variety of charcoal-containing devices are purported to minimize problems with odoriferous rectal gas; however, the evidence supporting the efficacy of these products is virtually all anecdotal. We objectively evaluated the ability of these devices to adsorb two malodorous, sulfide gases (hydrogen sulfide and methylmercaptan) instilled at the anus. METHODS: Via a tube, 100 ml of nitrogen containing 40 ppm of sulfide gases and 0.5% H(2) was instilled at the anus of six healthy volunteers who wore gas impermeable Mylar pantaloons over their garments. Since H(2) is not adsorbed by charcoal, the fraction of the sulfide gases removed could be determined from the concentration ratio of sulfide gas: H(2) in the pantaloon space relative to the ratio in instilled gas. RESULTS: Measurements with no device in place showed that subjects' garments removed 22.0 +/- 5.3% of the sulfide gases, and results obtained with each device were corrected for this removal. The only product that adsorbed virtually all of the sulfide gases was briefs constructed from an activated carbon fiber fabric. Pads worn inside the underwear removed 55-77% of the sulfide gases. Most cushions were relatively ineffective, adsorbing about 20% of the gases. CONCLUSIONS: The ability of charcoal-containing devices to adsorb odoriferous rectal gases is limited by incomplete exposure of the activated carbon to the gases. Briefs made from carbon fiber are highly effective; pads are less effective, removing 55-77% of the odor; cushions are relatively ineffective.

Absorption↗

Effects of the oral administration of a beta3-adrenergic agonist on lipid metabolism in alloxan-diabetic rats.

Previous studies have reported that beta3-adrenergic agonists regulate plasma glucose, triglycerides and free fatty acids in situations of hyperglycaemia and dyslipidaemia in rodents. In this study Trecadrine, a novel compound with affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not associated with statistical differences in plasma insulin levels, which may be explained by changes in insulin resistance and carbohydrate oxidation in peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%), which was not statistically significant, as well as in plasma triglycerides (from 1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine apparently induced lipolytic activity in adipocytes, as suggested by the increase of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free fatty acids decreased apparently through their utilisation in other tissues. Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P < 0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty acid oxidation may be enhanced in this tissue. These results give support to the possible therapeutic use of beta3-adrenergic compounds in situations of hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.

Absorption↗

Clinical and therapeutic aspects of AA amyloidosis.

Approach to the management of AA amyloidosis complicating RA. (A) In case of proteinuria or loss of renal function a rectal biopsy or a subcutaneous fat biopsy is a suitable screening method for the detection of amyloidosis. If in any doubt, try to ascertain the diagnosis by renal biopsy. Adequate staining with alkaline Congo red and preferably immunohistochemical staining with anti-AA antibodies should be performed. Beware of renal pathology other than amyloidosis even in the presence of a positive rectal biopsy. (B) A vigorous attempt to control disease activity of the RA should be made in order to eliminate the production of SAA, an acute phase protein. The response to treatment should be monitored by serial measurements of CRP and preferably SAA. (C) The function of some vital organs should be evaluated: (a) endogenous creatinine clearance and the extent of proteinuria; (b) electrocardiogram and optional echocardiography; (c) thyroid function and adrenocortical function; (d) intestinal absorption tests; (e) optional--SAP scintigraphy and turnover studies. (D) Attention should be given to adequate supportive treatment: (a) blood pressure control; (b) treatment of intercurrent infections; (c) corticosteroids during major surgical procedures; (d) pay attention to the possible effect of NSAID on proteinuria and renal function. (E) In case of total renal failure or uncontrollable proteinuria: (a) consider the possibility of primary renal transplantation; (b) otherwise regular haemodialysis is indicated.

Amyloidosis↗

N-Butyrate rectal transport in cirrhotic patients.

Data about colonic mucosa transport of short-chain fatty acids in cirrhotic patients are still lacking. The aim of the present study was to compare the rectal mucosa transport of n-butyrate and its effect on transport of other electrolytes and endoluminal pH in normal subjects and in cirrhotic patients by using a rectal dialysis technique. Thirteen subjects with normal hepatic function tests and 17 cirrhotic patients were enrolled. Dialysis bags containing 80 mmol/liter of butyrate in a neutral pH (6.8) electrolyte solution were placed in the rectum of enrolled subjects for 60 min. Net transport rate was calculated for butyrate, sodium, chloride, potassium, and bicarbonate. The differences in pH between initial and final dialysis solutions was also evaluated in the two groups in the study. Net butyrate absorption was significantly lower in cirrhotic patients than in controls (65.2 +/- 38.6 vs 101.2 +/- 45.3 nmol/min/cm2, respectively; P = 0.02). Furthermore, cirrhotic patients showed a lower HCO3 secretion than controls (-26.9 +/- 19.9 vs -45.1 +/- 20.0, respectively; P = 0.01). No differences were found in transport of the other electrolytes. The pH in the final dialysis solution in cirrhotic patients was not significantly lower than in the controls (7.15 vs 7.35; P = 0.1). In conclusion, the impairment of butyrate absorption and the concurrent reduction of bicarbonate secretion observed in cirrhotic patients may suggest a selective hypoactivity of apical HCO3-/SCFA- antiport located at the colonocyte apical membrane.

Absorption↗

Mechanisms of diarrhoea in myotonic dystrophy.

BACKGROUND: Gastrointestinal (GI) symptoms are common in myotonic dystrophy (MD). Diarrhoea is one of the more disabling of these GI complaints. The mechanisms behind diarrhoea in MD have not previously been investigated systematically. OBJECTIVE: To elucidate the mechanisms behind diarrhoea in MD. METHODS: Twenty patients with MD and suffering from diarrhoea were investigated in order to detect malabsorption (blood tests and faecal fat excretion) and bile acid malabsorption ([75Se]selenahomocholic acid-taurine (SeHCAT) retention) and to study intestinal morphology (duodenal and rectal biopsies). RESULTS: Two patients had deficiency of folic acid and four showed reduced levels of pancreatic isoamylase, but none of them had steatorrhoea. Two out of eight patients had abnormal bile acid breath tests with normal SeHCAT, indicating small bowel bacterial overgrowth and 12 displayed reduced SeHCAT retention. Duodenal biopsies were normal in eight patients and five out of nine rectal biopsies displayed slight inflammation. CONCLUSIONS: A possible mechanism of diarrhoea in MD could be identified in most of the patients. Bile acid malabsorption seems to be a frequent cause and can be treated successfully.

Adult↗

Effect of age and disease on the pharmacokinetics of nimesulide.

Nimesulide is a nonsteroidal anti-inflammatory agent with additional antipyretic and analgesic activity. The recommended dosage is 100 to 200 mg twice daily orally or rectally. The pharmacokinetics profile of nimesulide has been studied in patients with a predisposition for altered pharmacokinetics. The pharmacokinetic profile of nimesulide and its hydroxy metabolite was not altered when the drug was administered in a standard regimen (100mg twice daily) to elderly patients aged < 80 years, suggesting that dosage adjustment is not necessary for such patients. In children aged 7 to 9 years, nimesulide 50mg administered in a granular formulation showed a tendency for greater absorption and elimination than that recorded for adults administered nimesulide in tablet form. These results suggest that the pharmacokinetic profile of this paediatric formulation should be assessed in children aged < 7 years to determine whether their dosage should be adjusted. In patients with moderate renal insufficiency, the pharmacokinetic profile of nimesulide was not altered even though the terminal elimination half-life of its hydroxy metabolite was greater and this resulted in slight accumulation with multiple dose administration in a standard regimen. This slight effect was not considered to be clinically significant and therefore dosage adjustment for patients with moderate renal impairment appears unnecessary. Administration of nimesulide to patients with severe renal failure should be avoided until the propensity and significance of hydroxy-nimesulide accumulation is quantified in this patient group. The pharmacokinetic profile of nimesulide has not been determined in patients with hepatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Evaluation of salicin as an antipyretic prodrug that does not cause gastric injury.

Pharmacokinetic and pharmacological studies were performed to compare the antipyretic effects of salicin (SL), saligenin (SG, an aglycone of SL) and salicylic acid (SA, an active metabolite of SL) in rats. When SL was administered orally to rats, SA appeared slowly in the plasma and levels increased gradually, in contrast to the rapid appearance observed after oral administration of sodium salicylate (SANa) or SG. Orally administered SL did not affect the rectal temperatures of afebrile rats at a dose of 5 mmol/kg; at this dose, SANa and SG lowered body temperature significantly. However, it significantly reduced yeast-induced fever, producing a normal body temperature, and completely prevented fever when administered simultaneously with yeast. SL did not induce gastric lesions even at a dose of 5 mmol/kg; conversely, SANa and SG induced severe gastric lesions in a dose-dependent manner at 1, 2.5 and 5 mmol/kg. Poor absorption of SL and rapid absorption of SA and SG were confirmed in an in vivo system, as well as in an in vitro system using everted rat jejunal sacs. Only small amounts of SA and SG were detected in the intestinal tracts of rats 1 h after oral administration, whereas more than 50 % of an SL dose was recovered as SL and SG from the intestinal tracts 1 h after treatment and 15.8 % of the dose was still present as SG 4 h after administration. When given to germ-free rats, 19.8 % of the SL dose was recovered intact, mainly from the cecum, and no SG was detected even at 4 h after treatment. These results indicate that SL is a prodrug which is gradually transported to the lower part of the intestine, hydrolyzed to SG by intestinal bacteria, and converted to SA after absorption. It thus produces an antipyretic action without causing gastric injury.

Absorption↗

Cardiovascular, hematologic, and biochemical effects of acute ventral exposure of conscious rats to 2450-MHz (CW) microwave radiation.

In this study the influence of acute (6 hr) exposure to 2450 MHz (CW) microwave radiation on certain cardiovascular, biochemical, and hematologic indices was examined in unanesthetized rats. Under methoxyflurane anesthesia, a catheter was inserted into the right femoral artery, which was used for monitoring blood pressure, heart rate, and blood sampling. Colonic temperature was monitored via a VITEK thermistor probe inserted rectally to a depth of 5 cm. The rat was subsequently placed into a ventilated restraining cage which was located inside an anechoic chamber. The temperature and humidity in the chamber were maintained at 22 +/- 0.5 degrees C and 60 +/- 5% (means +/- S.E.), respectively, during the experimental period. Rats (60) were exposed to either 0 (sham) or 10 mW/cm2 (exposed) for 6 hr. During exposure rats were oriented perpendicular to the E-field, and the measured specific absorption rate (SAR) was 3.7 mW/g. In the sham and exposed rats, the preexposure (time 0) mean +/- S.E. arterial blood pressure (MABP), heart rate, and colonic temperature were approximately 120 +/- 5 mmHg, 450 +/- 10 beats/min, and 37.0 +/- 0.2 degrees C, respectively. In the sham-exposed rats these values remained stable throughout the 6-hr exposure period. In the exposed rats, no effects were noted on MABP or colonic temperature; however after 1 hr of exposure, a significant reduction in heart rate was noted (450 versus 400 beats/min). This decrease in heart rate persisted throughout the remainder of the exposure period. None of the hematologic or biochemical parameters examined were affected by the microwave exposure. Although other mechanisms may be responsible, this decrease in heart rate may have been due to subtle cardiovascular adjustments because of microwave-induced heating with a resultant reduction in resting metabolic rate.

Animals↗

Influence of cimetidine on steady state concentration and metabolite formation from antipyrine infused with a rectal osmotic mini pump.

The utility of an osmotic rectal drug delivery system as a tool in steady-state pharmacokinetic interaction studies has been investigated using the cimetidine-antipyrine interaction. Antipyrine was administered to six healthy male volunteers at the rate of 15 mg/h until steady-state was reached. Cimetidine 400 mg was then given followed by 200 mg cimetidine after 2, 4 and 6 h. Antipyrine kinetics in plasma and saliva were assessed, and metabolite excretion was determined in urine. Antipyrine levels in plasma and saliva increased shortly after cimetidine administration, indicating inhibition of antipyrine metabolizing enzymes. From the metabolite data it was concluded that all major metabolic pathways of antipyrine were affected to the same extent. The effect lasted somewhat longer than anticipated on the basis of the plasma cimetidine concentrations, but it had disappeared within 48 hours after cessation of treatment. It is concluded that the osmotic rectal drug delivery system is a useful tool in pharmacokinetic interaction studies, because it provides very constant steady-state concentrations, thus permitting investigation of the time course of drug interactions.

Adult↗

Cytological and enzyme-histochemical investigations on the digestive organs of Nautilus pompilius (Cephalopoda, Tetrabranchiata).

The foregut, stomach, caecum, midgut, and rectum of the digestive tract of Nautilus pompilius L.were investigated with ultrastructural and enzyme-cytological methods. Three different cell types were identified within the lamina epithelialis mucosae: main cells, goblet cells, and cells with secretory granules. The main cell type is the epithelial cell with microvilli, a basal nucleus surrounded by dictyosomes, rough endoplasmic reticulum, mitochondria, and electron-dense granules identified as lysosomes in the apical part of the cell. In the caecum this cell type contains endosymbiotic bacteria. The presence of endocytotic vesicles and the storage of lipids in the caecum indicate that this organ is involved in the process of absorption. In the caecum and the longitudinal groove of the rectum the main cells are, in addition, ciliated, facilitating the transport of food particles and faeces. Two types of goblet cells are found in all organs except in the stomach, forming a gliding path for food particles and protecting the epithelium. In the foregut and rectum, cells with electron-dense granules were recognized as the third type. The conspicuous secretory cells of the rectum represent a delimited rectal gland; its possible biological function is discussed. The tunica muscularis in all organs of the digestive tract consists of obliquely striated muscle cells innervated by axons containing transparent, osmiophilic and dense-cored vesicles. Positive reactions for acid and alkaline phosphatase, monoamine oxidase, beta-glucuronidase, and trypsin- and chymotrypsin-like enzymes are localized in the lamina epithelialis mucosae.

Animals↗

Duodenal obstruction in thyroid storm.

A 35-year-old, previously healthy woman, known to be thyrotoxic, was transferred from a community hospital for "acute abdomen." Abdominal pain, distention, and hyperemesis resolved with placement of nasogastric tube (NGT) and return of 2,600 mL of bilious fluid. Continued high NGT output made oral or NGT administration of antithyroid drugs impossible. We gave propylthiouracil (PTU) by retention enemas with therapeutic serum levels and sublingual saturated solution of potassium iodide (SSKI) with 70% absorption based on 24-hour free iodine urinary excretion. The patient's thyroxine (T4) and triiodothyronine (T3) radioimmunoassays were normal on hospital days 10 and 12, respectively. However, free T4 and T3 resin uptake did not normalize until hospital day 31. On hospital day 32, she tolerated removal of NGT without nausea and 4 days later was taking a regular diet. We conclude that our patient's gastrointestinal symptoms were a prominent feature of her thyrotoxicosis and that rectal PTU and sublingual SSKI are effective in administration of antithyroid drugs.

Abdomen, Acute↗

Effect of omeprazole on intestinal output in the short bowel syndrome.

Ten patients with an end jejunostomy and one with a jejuno-rectal anastomosis (jejunal length 30-140 cm) ate a constant chosen diet for 2 control days, and 2 test days when 40 mg omeprazole orally was taken each morning. In the 7 patients with a net secretory output of fluid, there was a mean reduction in wet weight of 0.66 kg/24 h (range -0.16 to 1.45 kg/24 h; P less than 0.05) and sodium 46 mmol/24 h (-51 to 135 mmol/24 h; N.S.); the four patients with net absorption of fluid showed no reduction in intestinal output. One patient with 30 cm jejunum responded little to oral but did so to intravenous 40 mg omeprazole twice a day with a reduction in wet weight of 3.00 kg/24 h and sodium 157 mmol/24 h. In one patient oral 40 mg omeprazole daily gave equivalent results to oral 300 mg ranitidine twice daily; in 2 others it was equivalent to intravenous 50 micrograms octreotide twice daily. Omeprazole reduces the intestinal output in patients with the short bowel syndrome and a net secretory output, but not enough to prevent the need for parenteral fluid and electrolyte replacement.

Anastomosis, Surgical↗

Enteropathy associated with the acquired immunodeficiency syndrome.

To explore the effect of the acquired immunodeficiency syndrome on gastrointestinal structure and absorption, the cases of 12 homosexual men with the syndrome and 11 homosexual controls were studied. Seven patients had diarrhea with weight loss. Bacterial or parasitic infections were not detected. All patients were malnourished; had significantly fewer T-lymphocyte helper and suppressor cells; and had significantly lower body weights, midarm circumferences, serum albumin concentrations, and iron binding capacities than homosexual controls. D-Xylose malabsorption and steatorrhea were present in patients, especially those with diarrhea. Jejunal and rectal biopsy samples were histologically abnormal in all patients with diarrhea. Jejunal abnormalities included partial villus atrophy with crypt hyperplasia and increased numbers of intraepithelial lymphocytes. Rectal abnormalities included intranuclear viral inclusions, mast cell infiltration in the lamina propria, and focal cell degeneration near the crypt base. The histologic findings suggest that a specific pathologic process occurs in the lamina propria of the small intestine and colon in some patients with the syndrome.

Acquired Immunodeficiency Syndrome↗

In vitro methods for the evaluation of drug availability from suppositories: comparison between biological and artificial membranes.

Drug availability from suppositories is currently evaluated in vitro by means of a model consisting of a dialysis tube (porous membrane) or isolated biological membrane (animal rectum). We propose a new alternative in vitro method to determine drug availability from suppositories consisting of an artificial membrane soaked with n-octanol, coupled with a filter paper sheet soaked with phosphate buffer. This method provides for an integrated hydro-lipophilic simulation of the biological membrane, including the mucus layer adhering to the rectal mucosa. By simply using the porous membrane, the amount of drug released varied directly according to its solubility for formulations with lipophilic excipients. For formulations with hydrophilic excipients, drugs with low/intermediate solubility in water showed increased availability in comparison to lipophilic excipients. The in vitro rat rectum model provided overall results that were similar to those obtained with the porous membrane method, although the percentage values of AUC were lower. The new model of in vitro simulated absorption produced a degree of drug availability that was lower in comparison to both previous methods. However, the simulated model appeared to give a pattern of drug availability closer to that of the model of in vitro rat rectum. The new in vitro artificial model thus appears to be useful in suppositories preformulation studies, allowing for an estimate of drug availability and the choice of the most adequate excipient.

Algorithms↗

[In vitro studies of drug liberation from suppositories with the rotating flask method].

The official dissolution apparatuses of the U.S.P. XXI or those recommended by the DAC 1979, respectively, are not suitable for the pertinent examination of rectal drug dosage forms. In the literature, on the other hand, numerous experimental setups have been proposed for the study of drug release from suppositories. However, these devices are all rather complicated as concerned with their construction as well as their handling, and, thus, cannot be considered as universally applicable test models. The rotating flask model, that has already been presented to the public earlier, in its two appearances, i.e. the dissolution tester (simple rotating flask) and the absorption model (compartmented rotating flask), can be employed for the testing of drug liberation from suppositories. The release parameters which have been determined in either of the two types of the rotating flask correlate well with each other and are also relevant characteristics of the bioavailability.

Chemistry, Pharmaceutical↗

Control of fluid transport in human rectal adenocarcinoma cells (HRA-19) in monolayer and collagen gel cultures.

HRA-19a1.1. cells, derived from a primary human rectal adenocarcinoma, form polarised monolayers when grown on tissue-culture plastic. HRA-19 monolayers have a heterogeneous morphology even after 150 passages in vitro or single cell cloning. The morphological changes observed in HRA-19 monolayers were postulated to be the result of vectorial fluid transport leading to accumulation of fluid between cells. To test this hypothesis, a variety of agents that control ion transport in colorectal epithelium were tested for their effect on HRA-19 morphology. Forskolin, cholera toxin and prostaglandin E2 all markedly changed HRA-19 monolayer morphology, with the rapid disappearance of intercellular spaces. These agents all stimulate Cl- secretion in colorectal epithelium, i.e. transport from basolateral to apical surface, and therefore would be expected to reduce fluid accumulation at the basolateral side of the cell. Conversely, vasopressin, which stimulates absorption of Na+ and water across colorectal epithelium, leads to a small increase in intercellular spaces in the monolayer. In collagen gel cultures, addition of cholera toxin, forskolin or prostaglandin E2 resulted in a large increase in colony size. In such treated cultures, the colonies were 'bubble-like', often composed of a single rim of flattened cells, which appeared to encompass a fluid-filled space. Similar morphological changes were observed when HRA-19 cells were co-cultured with 3T3 cells. This effect was probably due, at least in part, to prostaglandin production by the 3T3 cells, as the effect could be markedly reduced by the addition of indomethacin to these cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Differential distribution of galactosylceramide, H antigen, and carcinoembryonic antigen in rhesus macaque digestive mucosa.

The most common route of transmission of HIV is via the mucosa. We compared human and macaque intestinal epithelia to determine whether the SIV macaque system can be used as a model to study HIV transmission by the rectal route. The overall morphology of the macaque gut mucosa is very similar to that of humans. Differentiation markers follow the same pattern as in the human system. The carcinoembryonic antigen (CEA) is apical in epithelial cells of the rectum and is absent from the small intestine. Blood group H antigen is expressed by enterocytes but not by colonocytes or rectocytes. Galactosylceramide, a potential alternative receptor for HIV in epithelial cells, is expressed in all intestinal segments as in humans. In absorptive cells it is apical and intracellular in the rectum, colon, and cecum, whereas it is only intracellular in small intestine. In goblet cells the galactosylceramide is present in intracellular vacuoles in all segments. It is also present on the membrane of mucous granules in colon and small intestine but not in rectum. We therefore believe that the macaque digestive tract may constitute a good model for the human digestive tract in the transmission of lentiviruses.

Animals↗

Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.

A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.

Administration, Rectal↗