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PubMed1999

Physiological changes in spaceflight that may affect drug action.

Despite nearly 40 years of spaceflight, the paucity of time spent in microgravity and somewhat scattered approach to the study to pharmacology in microgravity have resulted in little solid information. Moreover, they have generally only been studied in the first few days of spaceflight or its simulation by bedrest, when physiological changes are most dynamic. Nevertheless, early physiological responses to microgravity have been well documented and provide good support for the hypothesis that both pharmacokinetics and pharmacodynamics should be altered, with more significant changes occurring as stays in space increase in duration. Whether given orally, by intravenous (IV) or intramuscular (IM) injection, intranasally (IN) or rectally, a drug must distribute through the body, usually crossing certain membranes and becoming bound to other molecules, reach its receptor and bind to it in order to exert its action. This paper, then, will follow a drug's passage through the body in terms of pharmacokinetic parameters known to be affected by microgravity, and mention other factors.

Adaptation, Physiological↗

PubMed1975

[The use of residue-free resorbable nutrient preparations in colonic surgery].

1. Our tests have shown that the use of the oral nutrient Vivasorb which is completely resorbed in the small intestine, allows patients to be prepared for a large bowel surgical procedure without having them fast. This nutrient guarantees the supply of all the necessary components of nutrition, including high caloric value. 2. The main effects that recommend the use of Vivasorb are: an improvement in the conditions for the healing of intestinal sutures because of the absence of intestinal contents and good trophic conditions in the intestinal wall. 3. The use of Vivasorb offers the possibility to avoid successive operations, e.g. with temporary fistulae. 4. The administration of Vivasorb allows the possibility to balance the nitrogen deficit which would otherwise result from fasting during the preparative stage before the operation and, additionally, from the increased turnover which persists during the post-operative phase. 5. We achieved good successes with the oral nutrient Vivasorb in our investigations, and in the operative treatment of large bowel and rectal carcinomas, and in cases of haemorrhoids and anal fistuale. Further investigations are being made. 6. We feel that it is favourable to use enemas during the preparative period, so that by removing the faeces remaining from the time before Vivasorb administration, the preparation period can be shortened without compromising the "sterility" of the large bowel.

Adult↗

PubMed1995

A semisynthetic Quillaja saponin as a drug delivery agent for aminoglycoside antibiotics.

PURPOSE: The purpose of this study was to investigate the utility of a purified, semisynthetic saponin, DS-1, prepared by deacylation of a naturally occurring saponin from the bark of the Quillaja saponaria Molina tree, as a permeation enhancer for mucosal delivery of the aminoglycosides, gentamicin and tobramycin. METHODS: Gentamicin or tobramycin formulations, with and without DS-1, were administered to rats nasally, ocularly, and rectally. Serum aminoglycoside levels following mucosal application were compared with those administered intramuscularly. Gentamicin formulations, with and without DS-1, were administered intranasally to mice 60 minutes after a lethal bacterial challenge. To ascertain nasal irritation potential, DS-1 nosedrops were administered to rats twice daily for 7 days in the right nostril only. Comparison of the left (internal control) and right nostril was made with a control group that received only buffer. RESULTS: Significant transport across mucous membranes was only observed in formulations containing DS-1. This effect on drug delivery was transient. Administration of an intranasal gentamicin/DS-1 formulation reversed the lethal bacterial challenge in mice, demonstrating that biological activity was retained after absorption. Nasal irritation was not observed in groups receiving DS-1 nosedrops, which were identical to control groups. CONCLUSIONS: DS-1 has potential as a transmucosal delivery agent for the aminoglycoside antibiotics.

Aminoglycosides↗

PubMed1979

Hyperchloremic acidosis and imperforate anus.

The predominant electrolyte imbalance associated with enterourinary fistulas is hyperchloremic acidosis. The mechanism is the absorption of urinary electrolytes across the colonic mucosa. One of the genitourinary associated anomalies of a high imperforate anus is a rectourinary fistula. There have been 5 cases of hyperchloremic acidosis as a complication of an imperforate anus with a rectourinary fistula reported in the literature to date. An additional case is presented with a clinical analysis of the previously reported cases. The important factors in the development of hyperchloremic acidosis in patients with an imperforate anus are 1) the presence of a rectourinary fistula, 2) an initial diverting colostomy permitting a long segment of colonic mucosa for the absorption of urinary electrolytes, 3) distal urinary tract obstruction allowing significant volumes of urine to flow into the colonic segment and 4) the presence of urinary tract infection contributing to the urinary obstruction. Management should consist of vigorous electrolyte therapy, decreasing the retrograde flow of urine into the colon by temporary catheterization and early repair of the fistulous tract.

Acidosis↗

PubMed1988

New surgical method to prevent pelvic radiation enteropathy.

Pelvic radiation doses exceeding 4,000-4,500 cGy are known to be associated with acute and chronic radiation enteropathy. This same radiation dose is, at the same time, only moderately effective in the elimination of microscopic malignancy, let alone gross clinical disease. Numerous medical and surgical attempts to minimize this complication have been uniformly unsuccessful. With the availability of a new synthetic, absorbable, polyglycolic acid mesh, an intestinal sling surgical procedure has been devised to exclude the small bowel from the pelvis and subsequent radiation fields. Twenty-five patients have been treated by this new technique with only one complication presenting as a fungal infection. Small-bowel barium contrast studies in 16 patients referred for postoperative radiation demonstrated 13 satisfactory exclusions of the small bowel from the translateral pelvic irradiation field. In 16 evaluable patients, three had unsatisfactory exclusion two of which were due to technical error. This has permitted high-dose (5,500-6,500 cGy) radiotherapy to the critical treatment volume without posttreatment complication. Mean follow-up time is 14.8 months. Several patients have been reexplored demonstrating complete absorption of the mesh without fibrinous adhesions or other foreign body reaction. It is concluded that this new technique of small bowel exclusion will permit the routine delivery of much higher doses of radiation in patients requiring improved local-regional control of their pelvic cancers and without morbidity from radiation-associated small bowel injury.

Aged↗

PubMed2002

Absorption and storage of phosphorus by larval Manduca sexta.

The role of phosphorus (P) in numerous important biological structures, coupled with the observation that P-content of many insect foods is disproportionately low, suggests that P may be a critical nutrient for growing insects - however, the few studies examining the effects of dietary P on insect performance have generally found only weak relationships. This mismatch may be reconciled by understanding the physiological mechanisms by which insects handle P. Here we describe P processing by larvae of Manduca sexta. When given un-manipulated leaves of a common host plant, Datura wrightii, fifth-instar larvae retained about 85% of P consumed; when given P-enriched leaves larvae retained only 25% of P consumed. Analysis of gut concentrations of P at four sites along the digestive tract, and in leaves and feces, indicates that the rectum is the primary site of P transport between the gut and body and that differences in P retention may be accounted for by differential rates of rectal P transport. Larvae given P-enriched leaves also showed an eightfold increase in the concentration of P in the hemolymph, primarily as alpha-glycerophosphate - but only a 12% increase in the concentration of P in body tissues, suggesting that hemolymph plays a central role in storage and buffering of P.

Journal Article↗

PubMed2004

The physical properties of rectal contents have effects on anorectal continence: insights from a study into the cause of fecal spotting on orlistat.

PURPOSE: The intermittent loss of oil or stool ("spotting") is an adverse effect that occurs in patients taking orlistat; the pathophysiology is unknown. This study was designed to investigate the local effects of orlistat, free fatty acids, and the effects of the physical properties of rectal contents on anorectal function and continence. METHODS: Anorectal physiology and continence function were assessed in ten healthy patients after the application of four test enemas: 1) high-viscosity stool substitute, 2) stool substitute with free fatty acid, 3) low-viscosity oil with placebo, 4) oil with orlistat. Rectal function and capacity were assessed by barostat techniques. Anal resting pressure, squeeze pressure, and squeeze duration were assessed by manometry. A retention test was performed using the same enemas as a quantitative assessment of continence. RESULTS: Orlistat and free fatty acid had no adverse effects on anorectal function or continence. For each enema, the maximum volume retained correlated with rectal capacity (r = 0.85; P < 0.01). Continence during rectal filling was better maintained for high-viscosity stool substitute than low-viscosity oil enemas (P < 0.03). Patients able to maintain effective squeeze pressure retained more of the low-viscosity enemas than those with short squeeze duration (P < 0.01); in contrast, the volume retained of high-viscosity enemas was unaffected by anal sphincter function. CONCLUSIONS: The physical properties of rectal contents, rectal capacity, and voluntary anal sphincter function have effects on continence function in healthy patients. The occurrence of spotting may depend on both intrinsic anorectal function and the effects of orlistat on the volume and physical properties of stool.

Administration, Oral↗

PubMed1999

Dye-enhanced selective laser ablation for surgical mucosectomy.

The diode laser operates at a wavelength of 805 nm; indocyanine green (ICG) has a maximum energy absorption of a wavelength of approximately 800 nm. The effect of the diode laser as a laser knife can be significantly enhanced with an injection of ICG. In the present study, this dye-enhanced photothermal effect was investigated in the field of surgical endoscopy. A 9-cm2 region of the canine gastric mucosa was removed by the laser after injection of 5 ml of ICG solution at a concentration of 0.5 mg/mL into the submucosal space. The diode laser was used at a power output of 10 watts. The canine stomach was removed 10 days after the operation to investigate the site histologically. Clinical application using transanal endoscopic microsurgery (TEM) was employed using a dye-enhanced laser in five patients with a rectal adenoma. The pathological changes in the canine gastric wall resected 10 days after the operation showed that the low-power laser enhanced by ICG produced less fibrosis in the submucosal space than electrocautery. Mucosal resection using a dye-enhanced laser was easily performed in these five patients. It was concluded that this easy removal of the mucosa by a dye-enhanced laser was due to its ability to produce hemostasis of the vessels and its excellent tissue-cutting effect.

Adenoma↗

PubMed1997

Delaying colostrum intake by one day has important effects on metabolic traits and on gastrointestinal and metabolic hormones in neonatal calves.

Effects on metabolic and endocrine traits of feeding colostrum on d 1 and 2, then mature milk up to d 7, or glucose or water on d 1, colostrum on d 2 and 3 and then mature milk up to d 7 were studied in calves. Calves fed colostrum within the first 24 h after birth had significantly higher rectal temperatures, heart rates and respiratory frequencies than calves provided only water or glucose. Significantly elevated plasma nonesterified fatty acid and bilirubin concentrations on d 1 and 2 of life in calves fed only water on d 1 compared with calves of the other groups mirrored reduced energy intake. Fecal consistency was significantly higher during wk 1 of life, and gastrin and glucose-dependent insulinotropic polypeptide increased only on d 1 and/or 2 of life in calves already fed colostrum on d 1, expressing improved functioning of the gastrointestinal tract. Significantly higher plasma globulin levels up to d 7 in calves fed colostrum on d 1 than in those starting colostrum intake only on d 2 demonstrated significantly enhanced efficiency of gamma-globulin absorption. Furthermore, significantly higher circulating glucose, albumin, insulin, insulin-like growth factor-I concentrations and significantly lower urea levels in calves fed colostrum on d 1 compared with those fed colostrum starting on d 2 of life indicated stimulation of anabolic processes. In conclusion, colostrum intake by calves within the first 24 h of life is needed not only for an adequate immune status, but also to produce the additional important and favorable effects on metabolic and endocrine traits and on vitality.

Animal Nutritional Physiological Phenomena↗

PubMed1995

Immediate hypersensitivity in the Flinders rat: further evidence for a possible link between susceptibility to allergies and depression.

Rats of the Flinders sensitive line (FSL, selectively bred for their increased cholinergic activity and used as a genetic animal model of depression) were compared with their control counterparts, the Flinders resistant line, for their susceptibility to anaphylaxis and the response of small intestinal tissues to the muscarinic agonist, bethanechol. Following sensitization to ovalbumin (OA), rats of both lines were challenged in vivo either with 3 mg OA i.p. or with saline. In spite of the absence of line-related differences in IgE titers, FSL rats were more susceptible to the induction of anaphylactic shock as evidenced by (1) more pronounced mast cell degranulation; (2) a greater drop in rectal temperature; (3) higher hematocrit values; and (4) changes in gut function characterized by an elevation of basal short-circuit current and increased conductance (indicating increases in transport tone and permeability) of the tissues mounted in Ussing chambers. Thus, this study provides further evidence for a common cholinergic mechanisms in susceptibility to both allergies and depression.

Anaphylaxis↗

PubMed1987

Time course of endotoxemia and cardiovascular changes in heat-stressed primates.

Heat stress causes a marked reduction in splanchnic blood flow in order to compensate for the increased flow to the skin. Splanchnic ischemia causes a leakage of endotoxins from the gut lumen into the portal circulation and, especially in the presence of a compromised reticuloendothelial system, may cause severe systemic endotoxemia. Since many of the pathological features of heat stroke are similar to the shock state produced by LPS, we examined whether heat-stress causes endotoxemia. Five anesthetized monkeys were subjected to an environmental temperature of 41 degrees +/- 0.3 degrees C and relative humidity of 100%, until death. Rectal temperatures were recorded continuously, blood pressure and ECG were recorded at 5-min intervals, and arterial blood samples were taken at 15-30 min intervals. A decline in mean arterial pressure and rapid rise in heart rate occurred at about 42 degrees C. Plasma LPS remained at 0.071 +/- 0.006 ng.ml-1 until a rectal temperature of +/- 42 degrees C. Thereafter, it increased slowly until beyond 43 degrees C when it rose rapidly to 0.347 +/- 0.024 prior to death. Endotoxemia may have been a contributing factor in the pathogenesis of heat stroke. If so, then the use of anti-LPS antibodies may be expected to be beneficial.

Animals↗

PubMed1984

Biopharmaceutical investigations of rectal suppositories. Part 1: Pharmaceutical and biological availability of theophylline.

The influence of suppository base and some tensides on the release and resorption of theophylline from model rectal suppositories was investigated in a preliminary way. It was established that the original Bulgarian suppository base Novosup ensures higher pharmaceutical and biological availability of theophylline in comparison with other investigated lipophilic bases. The preliminary inclusion of Tween 80 in Witepsol H 15 increased the pharmaceutical and biological availability of the drug. A linear relationship between the pharmaceutical and biological availability was observed after administration of model suppositories in rabbits.

Animals↗

PubMed1983

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. II. Blood group association.

Colorectal carcinoma patients' sera with ADCC antibody reacting with the HT-29 cell line (blood group A) generally (88%) cross-reacted with another group A cell line (COLO-394) but much less frequently (6-33%), with six tumor cell lines that did not express ABO blood group antigens. The findings suggested the possibility that the ADCC reactivity against the HT-29 cell line particularly by patients of blood group O is generally via "A" or "A-like" antigenicity of the target cells. This was supported by absorption studies that showed that the ADCC reactivity could be removed by blood group A but never by group B erythrocytes. Our results suggest that the prognostically favorable ADCC antibody in colorectal carcinoma patients' sera is of anti-blood group A specificity or cross reactivity.

ABO Blood-Group System↗

PubMed1996

Evaluation of suprapubic bladder aspiration for detection of group B streptococcal antigen by latex agglutination in neonatal urine.

Our objective was to determine whether urine collection by suprapubic bladder aspiration (SBA) improves the specificity of the group B streptococcal (GBS) latex agglutination (LA) test by avoiding contamination of urine with GBS from perineal and rectal colonization that can result in a positive LA test in an uninfected infant when the urine is collected by bag. Part 1 consists of a retrospective review of the medical records of 113 infants who had urine collected by SBA for GBS LA testing as part of evaluation for possible sepsis. The sensitivity and specificity of the urine LA test was assessed by comparing it with blood culture results. In part 2, a prospective analysis was performed of 19 newborns who had rectal and vaginal/penile cultures as well as urine by SBA and bag for GBS cultures and LA. Results of LA testing on urine collected by both of these methods were compared with results of urine, perineal, and rectal cultures. In the retrospective review of GBS LA testing performed on 113 consecutive urine specimens collected by SBA from neonates being evaluated for suspected sepsis, the sensitivity and specificity were 67% and 89%, respectively, when compared with blood culture results. Twelve infants who had a positive LA test result but a sterile blood culture (BC-,LA+) were compared with 95 infants with both blood cultures and urine LA tests negative for GBS (BC-, LA-). BC-, LA+ infants were more likely than those with BC-, LA- to have an immature to total neutrophil (I/T) ratio > or = 0.16 at 12 and 24 hours (p = 0.04 and 0.02, respectively). In the prospective study, we found that a positive GBS LA test can be due to perineal contamination and possibly to gastrointestinal absorption of GBS antigen. No false positive LA test results occurred on urine obtained by SBA; however, use of this method failed to detect the one infant with GBS bacteremia. Because of suboptimal sensitivity and specificity, use of the GBS LA test on urine obtained either by SBA or bag cannot be recommended for diagnosis of early onset GBS disease.

Antigens, Bacterial↗

PubMedDate not supplied

Trans-splenic portal scintigraphy in normal dogs.

The purpose of this study was to (1) establish a technique for ultrasound-guided trans-splenic portal scintigraphy (TSPS) using 99mTcO4(-), (2) evaluate portal vein morphology, (3) compare the radiation exposures for TSPS vs. per-rectal portal scintigraphy (PRPS), and (4) compare the quality of numerical data from the TSPS vs. PRPS. Eight juvenile dogs underwent PRPS and TSPS (minimum of 48h between studies) after initial screening tests. PRPS was done according to established protocol using 425 +/- 36MBq (mean +/- SD) of 99mTcO4(-). TSPS was done with the dogs in right lateral recumbency over the gamma camera. 99mTcO4(-) (57 +/- 13.9 MBq) was injected into the spleen 1-2s following initiation of the dynamic acquisition. The frame rate was 4 frames/s for 5 min. There was significantly lower radioactivity of 99mTcO4(-) given and significantly higher total counts recorded in the liver and heart during the TSPS compared with PRPS. The total counts for the TSPS and PRPS were 7120 +/- 4386 and 830 +/- 523, respectively. Percent absorption from the spleen was 52.5 +/- 19.1% compared with 9.2 +/- 5.7% for the colon. Calculated transit time for the TSPS studies was 7 +/- 2.3s. In TSPS studies, the splenic and portal veins were clearly identified. Radiation exposure levels of the dogs were significantly lower following TSPS than after PRPS. TSPS appears superior to PRPS as a method to image the portal venous system representing a valid alternative diagnostic test for animals with suspected portosystemic shunts.

Animals↗

PubMed1996

Colonization in the rectum and uterine cervix with group B streptococci may induce specific antibody responses in cervical secretions of pregnant women.

We have studied the relationships between genital or rectal carriage of group B streptococci (GBS) with the levels of systemic and mucosal antibodies to GBS in 200 women at about week 17 of pregnancy. Secretions from the uterine cervix were collected with absorbent cylindrical wicks for quantification of antibody levels with whole cell enzyme-linked immunosorbent assay. GBS were cultured from the cervix (with or without concomitant rectal colonization) of 13.5%, from the rectum (with or without concomitant cervical colonization) of 12%, and from both culture sites of 8.5% of the women. Serotypes Ia, II, and III were predominant. Compared with culture-negative women, the group of women colonized rectally had markedly elevated levels of both immunoglobulin A (IgA) and IgG antibodies to GBS in cervical secretions and also had a moderate but significant elevation of IgA antibodies in sera. Women colonized only in the cervix had increases of specific IgA and IgG antibodies in cervical secretions, but their serum antibody levels were not elevated. In cervical secretions, the increase in antibody levels in the groups of colonized women was most pronounced for the IgG isotype, indicating a mucosal immune response involving IgG as well as IgA. A close correlation was found among the levels of antibodies to each of the three GBS serotypes tested. Evidence for such cross-reacting antibodies to different serotypes of GBS, as well as to group A streptococci, was also obtained from absorption experiments. Altogether, our results show that undiluted secretions for antibody determination can be easily collected from the uterine cervix with absorbent wicks and demonstrate that colonization of GBS in the rectum and the uterine cervix may induce a systemic as well as a pronounced local immune response in the female genital tract. The findings may have implications for the development of a mucosal vaccine against GBS disease.

Adolescent↗

PubMed2001

New food components and gastrointestinal health.

Apart from its main functions of digestion, absorption and faecal processing, the human gastrointestinal tract has a complex pattern of muscular activity regulated by a largely autonomous nervous system, and its various organs contain large concentrations of immune and endocrine tissues. Any failure of these closely-integrated systems can lead to diseases ranging from the mildly irritating to the life threatening. Food contains a huge variety of chemical species, many of which are biologically active, and the distal regions of the gut are colonised by a rich and metabolically-active commensal flora that depend on nutrients derived ultimately from the host's dietary residues. The present paper explores the evidence for significant effects of food ingredients on functional bowel disorders, intestinal infections, and aspects of epithelial cell physiology involved in the development of colo-rectal neoplasia. Various strategies, including the manipulation of the colo-rectal microflora with pre- and probiotics, and the development of new products and plant varieties containing biologically-active constituents, have the potential to underpin the development of novel functional food products. However, these products will need to be based on proven biological principles, and fully tested for efficacy and safety. The rapidly-developing fields of functional genomics and cell biology will open up new experimental strategies to explore these possibilities, and emerging processing technologies seem likely to provide novel methods for their exploitation.

Bacteria↗

PubMed2006

Review article: aminosalicylates for distal colitis.

About two-thirds of patients with ulcerative colitis have an inflammatory involvement distal to the splenic flexure and therefore may be effectively treated with topical treatment. This allows the delivery of the active drug directly to the site of inflammation, limiting the systemic absorption and the potential side effects. Topical aminosalicylate therapy is the most effective approach, provided that the formulation reaches the upper extent of the disease. Suppositories should be considered the treatment of choice for proctitis and distal sigmoiditis. A 1 g Pentasa-suppository once daily induces a quicker clinical and endoscopic remission and was better tolerated than a 500-mg suppository twice daily. Enemas, foams and gel, thanks to their proximal spread, should be the treatment of choice for proctosigmoiditis and left-sided colitis. Oral aminosalicylates are less effective than topical therapies for patients with active disease; however, a combination of oral and topical aminosalicylates can be successfully tried in refractory patients. Topical aminosalicylates also play an important role in the maintenance of remission, and the combination of oral plus rectal 5-aminosalicylate is superior to the single agent. Patients who prefer not to continue on long-term rectal therapy can be treated with oral aminosalicylates.

Aminosalicylic Acids↗