NSAIDs and the GI tract—potential hazards and benefits

Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have a substantial impact upon the gastrointestinal tract with both toxicity and benefit. The major toxicity relates to gastroduodenal ulceration and injury to the small and large intestine. The major benefits relate to evidence that the drugs may prevent, delay or cause regression of progress towards malignancy in the colon, and almost certainly also the stomach. The mechanism of toxicity has been thought to relate to inhibition of the synthesis of prostaglandins, since these are protective to the gastrointestinal mucosa as a result of effects on blood flow and mucus and bicarbonate secretion. It is difficult to attribute any anti-cancer effect to these actions. Promotion of apoptosis, which appears to be independent of prostaglandin synthesis, may better account for both therapeutic benefits and possibly some of the toxicity.     

“In vivo” pH values of the estrous reproductive tract of the gilt

The hydrogen ion concentration of the fluids of various portions of the reproductive tract was determined in 6 estrous gilts. Determinations were made with a pH cardiovascular catheter electrode placed in the lumen of the oviduct, uterus, cervix and vagina and a reference electrode placed in the peritoneal cavity. The mean pH values were 7.02, 6.98, 7.49, and 6.61 for the oviduct, uterus, cervix and vagina, respectively.     

Do neocortical pyramidal neurons display stochastic resonance?

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity that has a significant impact on various electrophysiological properties and dendritic integration. Using detailed biophysical models of a morphologically reconstructed neocortical pyramidal neuron, in which synaptic background activity was simulated according to recent measurements in cat parietal cortex in vivo, we show that the responsiveness of the cell to additional periodic subthreshold stimuli can be significantly enhanced through mechanisms similar to stochastic resonance. We compare several paradigms leading to stochastic resonance-like behavior, such as varying the strength or the correlation in the background activity. A new type of resonance-like behavior was obtained when the correlation was varied, in which case the responsiveness is sensitive to the statistics rather than the strength of the noise. We suggest that this type of resonance may be relevant to information processing in the cerebral cortex.     

Do type 1 fimbriae promote inflammation in the human urinary tract?

Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.     

Brushing cytology of the upper gastrointestinal tract. Obsolete or not?

The merit of brushing cytology of the upper gastrointestinal tract has been questioned since it appears to duplicate biopsy. To determine its value, the reports on all endoscopic biopsy and cytology specimens from a one-year period were reviewed. The 683 procedures included 481 in which only a histologic biopsy sample was obtained, 47 in which only a cytologic brushing sample was obtained and 155 in which both types of samples were obtained ("combined specimens"). Among the 155 combined specimens, 4 of the confirmed malignancies were detected by histology only while 2 were detected by cytology only. A diagnosis of suspicious or positive for malignancy was made for 20% of the combined specimens as compared to less than 5% of the biopsy-only or brushing-only specimens. While 15% of the specimens that included a brushing sample (either alone or with biopsy) showed fungal infections, only 1.2% of the biopsy-only specimens did. It appears that the clinicians at this hospital tend to use brushing in combination with biopsy when either a malignancy or a fungal infection is suspected. Other empiric advantages of endoscopic brushing cytology include its rapid turn-around time, minimal invasiveness and good recognition of lymphoid cells. The selective use of brushing cytology should increase the probability of detecting malignancies and fungal infections without any increased risk or discomfort to the patients.     

Does the lateral bundle of the medial olfactory tract mediate reproductive behavior in male crucian carp?

The olfactory tract in crucian carp (Carassius carassius) is divided into three distinct bundles: the lateral tract (LOT) and the lateral (lMOT) and medial (mMOT) bundles of the medial tract. The LOT has been shown to mediate information associated with feeding behavior, whereas the mMOT mediates information associated with alarm response. The role of the medial olfactory tract (lMOT and mMOT) in reproductive behavior is still under debate. In the present experiment, male reproductive behavior towards prostaglandin-injected females was investigated before and after cutting off the different olfactory tract bundles, to determine which of the tract bundles is essential for mediating reproductive behavior in male crucian carp. The fish were maintained in physiological saline before and after surgery to preserve the remaining tract bundles. Operations were performed symmetrically on both sides and post-operative inspections revealed the functionality of the intact tracts. Sham-operated males and males with only the lMOT intact showed typical reproductive behavior, with following of the female and inspections of the female anal papilla. However, males in which the lMOT was cut, leaving both the mMOT and the LOT intact, showed reduced reproductive behavior. Our results suggest that the lMOT mediates reproductive behavior in male crucian carp.     

Is feeding behaviour in crucian carp mediated by the lateral olfactory tract?

Experiments were performed to investigate which bundle of the olfactory tract was essential for mediating feeding behaviour in crucian carp. Fish were divided in three groups: control fish, fish with only the lateral olfactory tracts (LOTs) intact and fish with the LOTs cut. The fish were maintained in physiological saline after surgery to preserve the remaining tracts and postoperative inspections revealed the functional status of the remaining tracts. With the injection of food odour into the aquaria the scores for various feeding behaviours--biting, snapping, mouth openings and vertical posture--were not significantly different between those of the control fish and the fish with the LOT intact. Those fish that had the LOT cut but the medial and lateral parts of the medial olfactory tract (mMOT, lMOT) intact had significantly lower feeding-related scores than the other two groups of fish. The results of the present study indicate that the LOT is necessary to maintain the full qualitative and quantitative extent of feeding behaviour in crucian carp.     

Timing and irreversibility of Müllerian duct inhibition in the embryonic reproductive tract of the human male

A study was undertaken to determine (1) the effects of endogenous Müllerian inhibiting substance (MIS) on the developing human fetal genital tract; (2) the time in fetal life when MIS is first capable of inhibiting the growth of the embryonic Müllerian ducts; and (3) the reversibility of the effects of MIS on the developing male Müllerian ducts. Human fetal reproductive tracts were transplanted and grown for sustained periods in vivo in athymic nude mice. The genital tracts from 12 male human fetuses, ages 51 to 68 days postovulation, were grafted without their associated gonads into castrated murine hosts and grown for 30 to 70 days. Controls consisted of genital tracts from 8 female human fetuses, ages day 53 to 70 that were grown under identical conditions. Male specimens grew to approximately one-half the size of female specimens and disclosed varying degrees of inhibition of the Müllerian duct system from absence of the Müllerian ducts in older specimens (after Day 63) to poorly segregated segments of stroma as the mildest defect (less than Day 61). It is concluded that (1) MIS secretion by the embryonic testes probably begins before Day 51 of gestation; (2) the effects of MIS are progressive during the so-called critical window; (3) the effects of MIS are permanent; and (4) the mesenchyme is an important target of MIS.     

Different effects of α- and γ-glycine on the aberrant activity of pyramidal neurons of hippocampal slices

Experiments in vitro on hippocampal slices of mouse have shown that solutions prepared from polymorphic modifications α- and γ-glycine have different effect on the aberrant activity of neurons. In the presence of α-glycine the excitability of these neurons decreased more slowly, prolonging its modulating effect on NMDA type glutamate receptors. This effect agrees with higher biological activity of α-polymorphic modifications (as compared with that of the α-form) that previously observed with respect to behavior of mice from the line with genetic diathesis to catalepsy, which were used as a biological model for investigation of some pathological behavior forms.     

In vitro studies on calcium absorption from the gastrointestinal tract in␣small ruminants

Unidirectional flux rates of Ca²⁺ across gastrointestinal tissues from sheep and goats were measured in vitro by applying the Ussing-chamber technique. Except for the sheep duodenum, mucosal to serosal Ca²⁺ flux rates (J _ms) exceeded respective flux rates in the opposite direction (J _sm) in both species and in all segments of the intestinal tract. This resulted in net Ca²⁺ flux rates␣(J _net = J _ms − J _sm) ranging between −2 and 9 nmol · cm⁻² · h⁻¹ in sheep and between 10 and 15 nmol cm⁻² · h⁻¹ in goats. In sheep, only J _net in jejunum, and in goats, J _netin duodenum and jejunum were significantly different from zero. Using sheep rumen wall epithelia, significant J _net of Ca²⁺ of around 5 nmol · cm⁻² · h⁻¹ could be detected. Since the experiments were carried out in the absence of an electrochemical gradient, significant net Ca²⁺ absorption clearly indicates the presence of active mechanisms for Ca²⁺ transport. Dietary Ca depletion caused increased calcitriol plasma concentrations and induced significant stimulations of net Ca²⁺ absorption in goat rumen. J _net of Ca²⁺ across goat rumen epithelia was significantly reduced by 1 mmol · l ⁻¹ verapamil in the mucosal buffer solution. In conclusion, there is clear evidence for the rumen as a main site for active Ca²⁺ absorption in small ruminants. Stimulation of active Ca²⁺ absorption by increased plasma calcitriol levels and inhibition by mucosal verapamil suggest mechanistic and regulatory similarities to active Ca²⁺ transport as described for the upper small intestines of monogastric species. Accepted: 31 July 1996     

Effects of cereal β-glucans and enzyme inclusion on the porcine gastrointestinal tract microbiota

This study was designed to evaluate the effect barley-based diets vs. oats based diets on levels of Lactobacillus, Bifidobacterium and Enterobacterium in the porcine gastrointestinal tract (GIT). In addition the effect of enzyme supplementation in both diets was explored. Twenty-eight boars were used in a 2 × 2 factorial arrangement and were assigned to 1 of 4 dietary treatments: barley-based (B) diet; barley-based diet plus an enzyme supplement (B + ES); oat-based (O) diet or oat-based diet plus an enzyme supplement (O + ES). The enzyme supplement contained endo-1,3-β-glucanase and endo-1,4-β-xylanase. Faecal samples were collected from the pigs prior to initiations of the experiment and at slaughter. At slaughter digesta samples were collected from the stomach, ileum, caecum, proximal and distal colon. Alterations in Lactobacillus species composition in the gastrointestinal tract (GIT) were analysed by genus-specific PCR – denaturing gradient gel electrophoresis (DGGE). DGGE profiles indicated that cereal source provoked shifts in Lactobacillus population. The most diverse populations of lactobacilli emerged after feeding the O diets. Enzymes inclusion altered the composition of Lactobacillus species prevalent throughout the GIT in animals fed the B diet, causing a shift in the dominant lactobacilli present in the caecum and proximal colon. No such effect was evident in animals fed the enzyme supplemented O + ES diet. Microbial plate counts revealed that the O diets gave rise to higher counts of Lactobacillus in the caecum and colon and Bifidobacterium counts in the ileum, caecum and colon than the B diets. The O diet caused a 2 log increase in Enterobacterium counts in the proximal colon, no such effects were observed in animals fed the B, the B + ES or the O + ES diets. Overall both O diets had a more positive influence on the counts of the beneficial microorganisms and richness of the Lactobacillus population in the porcine GIT.     

Immunocytochemical localization of a novel pituitary polypeptide “7B2” in the gastro-intestinal tract of the rat

Summary Immunoreactivity to the polypeptide designated 7B2 recently isolated from human and porcine pituitary glands, appears to be consistently confined to neuroendocrine and endocrine cells in various tissues. In rat gut, immunoreactive 7B2 was found in endocrine-paracrine cells. Highly labeled cells were found in the antrum of the stomach and, cells with lower concentrations, in the fundus, duodenum, jejunum and ileum. Except for a few cells which were simultaneously positive for 5-hydroxytryptamine, and a few others showing Grimelius's reaction, 7B2 cells do not exhibit argentaffin and/or argyrophil character. The 7B2 polypeptide seems to be distributed amongst several different types of endocrine cells in the gut.     

Obstruction of the fetal urinary tract: a role for surgical intervention in utero?

Obstruction of the lower urinary tract was diagnosed by ultrasound in 11 fetuses. One pregnancy was therapeutically aborted. Four of the neonates died within 48 hours because of pronounced pulmonary hypoplasia, which is associated with obstruction of the urinary tract. The remaining six survived with adequate renal function but one, now aged 4, is obviously too small for his age. Intervention in utero for obstruction of the urinary tract is safe, but those fetuses for whom it is appropriate cannot yet be identified because of difficulties in diagnosing the condition of the whole fetus.     

Expression of α-taxilin in the murine gastrointestinal tract: potential implication in cell proliferation

α-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker. To gain insight into the physiological role of α-taxilin in normal tissues, we examined α-taxilin expression by Western blot and performed immunochemical analysis in the murine gastrointestinal tract where cell renewal vigorously occurs. α-Taxilin was expressed in the majority of the gastrointestinal tract and was prominently expressed in epithelial cells positive for Ki-67, a marker of actively proliferating cells. In the small intestine, α-taxilin was expressed in transient-amplifying cells and crypt base columnar cells intercalated among Paneth cells. In the corpus and antrum of the stomach, α-taxilin was expressed in cells localized in the lower pit and at the gland, respectively, but not in parietal or zymogenic cells. During development of the small intestine, α-taxilin was expressed in Ki-67-positive regions. Inhibition of cell proliferation by suppression of the Notch cascade using a γ-secretase inhibitor led to a decrease in α-taxilin- and Ki-67-positive cells in the stomach. These results suggest that expression of α-taxilin is regulated in parallel with cell proliferation in the murine gastrointestinal tract.     

Sperm storage in the vertebrate female reproductive tract: How does it work so well?

The capacity for sperm storage within the female reproductive tract occurs widely across all groups of vertebrate species and is exceptionally well developed in some reptiles (maximum duration, 7 yr) and fish (maximum duration, >1 yr). Amphibians (most salamanders and one species of frog; duration approximately 5 mo), all birds examined to date and some bats, have also evolved the ability to store spermatozoa in the female reproductive tract. Although there are many reports on both the occurrence of female sperm storage and its adaptive benefits, few studies have been directed toward explaining the mechanisms involved. Phylogenetic evidence suggests that the capacity for sperm storage has evolved independently within different taxonomic groups, and it is by no means clear whether these groups have established similar or different mechanisms or whether simple and common principles have been exploited during evolution. If the process has indeed developed by the invention of numerous different and species-specific mechanisms, it is surprising that none have yet been elucidated by technologists wishing to improve the long-term storage of fresh semen. On the other hand, if there is a simple and common solution to the problem, readily accessed by diverse groups of species, it is equally logical to suppose that the mechanism should be easily discovered in the laboratory. While recognizing that studies on wild species are usually neither practically or ethically easy to undertake, it is clear that there is a huge and largely unexplored field to be investigated.