Absorption of amino penicillins from everted rat intestine

1. Using an in vitro everted gut sac method based on that of Wilson & Wiseman (1954), a number of amino penicillins were tested in order to identify the involvement of any specialized transport mechanisms in their absorption across rat intestine. 2. Only one of the amino penicillins, cyclacillin (1-amino-cyclohexyl penicillin) was shown to be actively transported. The other penicillins appeared to diffuse passively across the intestine. 3. Cyclacillin was found to concentrate against a gradient at 37 degrees C but not at 19 degrees C. 4. Transport of cyclacillin across the mucosal membrane was saturated at mucosal concentrations greater than 1000 microgram/ml. 5. The rate of the forward flux of cyclacillin was many times that of its back flux. 6. No relationship between the active transport of cyclacillin and that of amino acids could be demonstrated.     

Small intestinal dysmotility following abdominal irradiation in the rat small intestine

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6-8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (> 20 mmHg, long-duration > 6 sec) pressure waves, and long (> 20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of > 20 pressure waves.     

Studies on the composition of phospholipids in rat small intestinal smooth muscle

The phospholipid composition of rat small intestinal smooth muscle was investigated in comparison with those of the mucosa and liver. Phospholipid content per g of the wet smooth muscle was almost identical with that of the mucosa and was about 1/4 of that in the liver. The phospholipid/protein ratio of the smooth muscle was about 1/2 of the value in the liver. Sphingomyelin content was significantly high and amounted to 18% of total phospholipids. This value was about twice that in the mucosa and 4 times higher than that in the liver. On the other hand, the percent distribution of phosphatidylcholine was lowest in the smooth muscle. Distribution patterns of phosphatidylserine and phosphatidylinositol in the smooth muscle as well as in the mucosa were different from those in the liver. The occurrence of vinyl-ether and ether phospholipids was clearly demonstrated in the smooth muscle as well as in the mucosa. A major part of the ether lipids was detected in the phosphatidylethanolamine fraction, in which they amounted to about 50%; 40% as alkenyl-acyl type and 12% as alkyl-acyl type. A high content of ether lipids was also observed in the phosphatidylethanolamine fraction from mucosa, but the distribution was reversed, that is, 14% alkenyl-acyl type and 28% alkyl-acyl type. Fatty aldehydes, fatty alcohols, and fatty acids were also determined by gas-liquid chromatography. The compositions of fatty aldehydes in the phosphatidylethanolamine fraction from smooth muscle and from mucosa were similar, whereas the compositions of long chain fatty alcohol and fatty acids were clearly different. The compositions of fatty alcohols and fatty acids of the phosphatidylcholine fraction from smooth muscle showed significantly different patterns from those of the phosphatidylethanolamine fraction and from those of the same phospholipid fraction in the mucosa.     

The effect of the live weight of rats on the intestinal in vitro absorption of nickel using everted intestinal sacs

The influence of the live weight of the experimental animals on the Ni absorption was investigated in vitro with everted sacs from rats. Totally 75 male rats in the live weight range from 30 to 250 g were used. With increasing live weight the Ni uptake by the intestinal wall and the Ni transfer across the intestinal wall decreased significantly. Ni transfer was already significantly reduced by 45% when body weight increased from 30 to 60 g. For the animals with a live weight above 200 g Ni transfer reached only about 10% of the Ni transfer measured for the animals with 30 g live weight. The decline of the Ni uptake by the intestinal wall was only slightly in the live weight range from 30 to 150 g. Within the live weights higher than 190 g Ni uptake by the intestinal wall decreased significantly to about 25% compared to the animals with 30 g live weight.     

Effect of vitamin A on small intestinal brush border enzymes in a rat

To determine the utility of the myocardial tracer Tc-99m-tetrofosmin in the examination of patients with left bundle branch block (LBBB) and to investigate Tc-99m-tetrofosmin uptake and retention in the myocardium, early and delayed Tc-99m-tetrofosmin SPECT was performed in 10 patients having LBBB without coronary stenosis. METHODS: After 740 MBq of Tc-99m-tetrofosmin injection in the resting state, the early and delayed SPECT imaging was done at 30 min and 180 min, respectively. RESULTS: Decreased Tc-99m-tetrofosmin uptake in the septal segments was observed in 4 patients (40%) at 30 min and in 9 (90%) at 180 min. Reverse redistribution was seen in 9 of 10 patients. In patients with LBBB, the septal-to-lateral uptake ratio was lower in the delayed images than in the early images (0.80 +/- 0.09 vs. 0.89 +/- 0.09, p < 0.001). In patients with LBBB, the washout rate of Tc-99m-tetrofosmin was higher in the septal segments than in the lateral segments (28.3 +/- 4.3% vs. 22.8 +/- 3.3%, p < 0.001). CONCLUSION: The SPECT data indicate that in LBBB without coronary stenosis, the uptake of Tc-99m-tetrofosmin is decreased in the septal wall, and that reverse redistribution occurs frequently. Our results contribute to the elucidation of both the cellular biokinetics of Tc-99m-tetrofosmin in the myocardium and the hemodynamics of the septum in LBBB, and indicate the possible clinical utility of Tc-99m-tetrofosmin.     

Macrophage inflammatory protein-2: chromosomal regulation in rat small intestinal epithelial cells

Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown. Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1beta (IL-1beta) and incubated with sodium butyrate. Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2. However, lipopolysaccharide and IL-1beta induced MIP-2 expression. Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1beta-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells. Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1beta. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion. Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines.     

Role of mechanical stimulation in maintaining small intestinal mass in Thiry-Vella loops in the rat

Two 10-cm long Thiry-Vella (TV) loops were constructed in each of 20 rats. An elastic-plastic device, which served as a source of continuous intraluminal mechanical stimulation, was fixed in one of the loops. Two weeks later the jejunum, ileum and both TV-loops were biopsied. Wet and dry weight per 3 cm intestine, villus height and muscular thickness, were determined. Both TV loops were atrophic, but the wet and dry weight and muscular thickness were significantly greater in the mechanically stimulated ones. The villus height was not significantly effected by the mechanical stimulation. The experiments demonstrate that the effect of mechanical stimulation on the food-deprived small intestine is limited to a certain extent of muscular hypertrophy resulting in a lesser degree of atrophy expressed in terms of wet and dry weight of the intestine.     

Interaction of a self-emulsifying lipid drug delivery system with the everted rat intestinal mucosa as a function of droplet size and surface charge

OBJECTIVES: Recovery from focal motor pathway lesions may be associated with a functional reorganisation of cortical motor areas. Previous studies of the relation between structural brain damage and the functional consequences have employed MRI and CT, which provide limited structural information. The recent development of diffusion tensor imaging (DTI) now provides quantitative measures of fibre tract integrity and orientation. The objective was to use DTI and functional MRI (fMRI) to determine the mechanisms underlying the excellent recovery found after a penetrating injury to the right capsular region. METHODS: DTI and fMRI were performed on the patient described; DTI was performed on five normal controls. RESULTS: The injury resulted in a left hemiplegia which resolved fully over several weeks. When studied 18 months later there was no pyramidal weakness, a mild hemidystonia, and sensory disturbance. fMRI activation maps showed contralateral primary and supplementary motor cortex activation during tapping of each hand; smaller ipsilateral primary motor areas were activated by the recovered hand only. DTI disclosed preserved structural integrity and orientation in the posterior capsular limb by contrast with the disrupted structure in the anterior limb on the injured side. CONCLUSIONS: The findings suggest that the main recovery mechanism was a preservation of the integrity and orientation of pyramidal tract fibres. The fMRI studies do not suggest substantial reorganisation of the motor cortex, although ipsilateral pathways may have contributed to the recovery. The initial deficit was probably due to reversible local factors including oedema and mass effect; permanent damage to fibre tracts in the anterior capsular limb may account for the persistent sensory deficit. This study shows for the first time the potential value of combining fMRI and DTI together to investigate mechanisms of recovery and persistent deficit in an individual patient.     

Survival in small intestinal adenocarcinoma

All cases of adenocarcinoma in the duodenum (n = 263) and jejunum/ileum (n = 663), diagnosed between 1960 and 1988, were recruited from the Swedish Cancer Registry. Corrected and overall survival were investigated by sex, age and year of diagnosis with life-table and Cox proportional hazards analyses. The corrected 5- and 10-year survival rates were 39% and 37% for duodenal tumours and 46% and 41% for those in jejunum/ileum (P = 0.16 for difference between sites). The corrected 5- and 10-year survival rates were 52% and 48% for women and 40% and 34% for men with tumours in jejunum/ileum (P = 0.0095 for difference by sex) while no such relation was found in duodenal tumours (P = 0.84). Survival correlated with age at diagnosis for duodenal tumours (P = 0.03377). A Cox proportional hazards analysis revealed a temporal trend with more favourable prognosis in recent years. This study confirms that prognosis of small bowel adenocarcinoma is serious, but gives a more optimistic outlook than many hitherto published series.     

Effect of aging on the intestinal transport of hydrophilic drugs in the rat small intestine

The effect of aging on the intestinal transport of hydrophilic drugs (and probe compounds) was investigated in the rat small intestine. Passive transport was suggested to be unchanged with aging from 8 (young) to 54 (old) and further to 101 (very old) weeks old, as shown for D-xylose and urea in single-pass intestinal perfusion (under urethane anesthesia), where steady-state transport across the intestinal membrane into the blood stream was evaluated. The passive transports of cephradine, 5-fluorouracil (5-FU) and L-glucose were also unchanged, though they were compared only between the young and the old. Consistently, the passive uptake in the intestinal everted sacs, where the entry process into the membrane was evaluated for 5-FU, D-xylose, urea and polyethylene glycol (PEG) 900, was unchanged with aging from the young to the very old. The carrier-mediated transport of cephradine was also unchanged with aging from the young to the old in perfusion under anesthesia, though that of D-glucose was declined by about 50% with aging from the young to the old and thereafter remained constant in the very old. In perfusion in unanesthetized rats, age independency in passive transport (examined for cephradine, L-glucose and D-xylose) and an age-dependent decline in D-glucose transport were also observed, suggesting that the findings under anesthesia are not qualitatively distorted. These results suggest that, although carrier-mediated transport may moderately decline with aging, the barrier function of the intestinal membrane to passive permeation of hydrophilic drugs (with molecular weight below 1000) may be unaffected by aging, supporting the suggestion from our previous in vivo studies that age-dependent increases in the orally absorbed fraction may be predicted for incompletely absorbed drugs because of delayed intestinal transit rather than increased intestinal transport (membrane permeability).     

Histological and functional studies of small intestinal mucosa in intestinal tuberculosis

Twelve cases of peptic ulcer with diabetes mellitus were found in 165 hospitalized diabetics. All of them had gastric ulcer and no duodenal ulcers were found. The incidence of peptic ulcer in diabetics was comparatively higher than the previously reported series. But there was nosignificant correlation between the duration of diabetes and the onset of gastric ulcer. The gastric ulcer with poorly controlled diabetes showed more intractability than those without triopathy and well-controlled diabetes.     

The role of cyclic guanylate monophosphate in nitric oxide-induced injury to rat small intestinal epithelial cells

PURPOSE: Biostatistical models predicting the risk of recurrence after radical prostatectomy for clinically localized prostate cancer are necessary. Identifying these high risk patients shortly after surgery, while tumor burden is minimal, makes them candidates for possible adjuvant therapy and/or investigational phase II clinical trials. This study builds on previously proposed models that predict the likelihood of early recurrence after radical prostatectomy. MATERIALS AND METHODS: In our analysis we evaluate age, race, prostatic acid phosphatase and nuclear grade with the established prognostic variables of pretreatment prostate specific antigen, postoperative Gleason sum and pathological stage. RESULTS: After multivariable Cox regression analysis using only statistically significant variables that predicted recurrence we developed an equation that calculates the relative risk of recurrence (Rr) as: Rr = exp[(0.51 x Race) + (0.12 x PSAST) + (0.25 x Postop Gleason sum) + (0.89 x Organ Conf.). These cases are then categorized into 3 distinct risk groups of relative risk of recurrence of low (< 10.0), intermediate (10.0 to 30.0) and high (> 30.0). Kaplan-Meier survival analysis of these 3 risk groups reveals that each category has significantly different risks of recurrence (p < 0.05). This model is validated with an independent cohort of radical prostatectomy patients treated at a different medical center by multiple primary surgeons. CONCLUSIONS: This model suggests that race, preoperative prostate specific antigen, postoperative Gleason sum and pathological stage are important independent prognosticators of recurrence after radical prostatectomy for clinically localized prostate cancer. Race should be considered in future models that attempt to predict the likelihood of recurrence after surgery.     

Techniques of intestinal transplantation in rat

Two surgical models of intestinal transplantation in the rat are described. One is the implantation of fetal and newborn intestine as free grafts into the omentum of adult recipients, the other the adult intestine transplantation as an accessory graft using vascular anastomoses. A hundred and sixteen small-bowel transplantations were done; 36 of which were fetal intestine (group I), 40 of newborn intestine (group II), and 40 of adult intestine (group III). In the fetal and newborn intestinal transplantation, we emphasize the practices that allowed us to avoid ischemic and traumatic injury to the graft. In the adult intestine transplantation with vascular anastomoses, we heighten the modifications in the surgical technique that made the operation easier and the strategies used to prevent hypothermia and hypovolemic shock. Once experienced with the two chosen surgical techniques, transplantation using an avascular segment became much easier and quicker than transplantation with vascular anastomoses.     

Intestinal hypertrophy after small intestinal bypass in the rat. Studies on methods and reversibility of changes

This study assessed sex differences in spontaneous wheel running and maze performance in relation to puberal status in rats. No sex differences were found prepuberally in either task whereas, postpuberally, females exceeded males in wheel running and males made fewer maze errors than females. Postpuberal males and females were less active than independent groups of prepuberal males and females, respectively. Although mature females made more errors than prepuberal females, no differences were found between independent groups of pre- and postpuberal males.     

UDP-glucuronosyltransferase UGT1A7 induced in rat small intestinal mucosa by oral administration of 2-naphthoflavone

Cerebellar basket cells form highly specialized inhibitory synaptic contacts with Purkinje cells, namely the pericellular basket and pinceau nerve terminal structures, wrapping around the Purkinje cell somatic and axon hillock regions. These inhibitory synaptic contacts are ideally located to control the ultimate output of the cerebellar cortex. Previous immunohistochemical studies have shown that these synaptic structures possess a very high density of the dendrotoxin (DTX)-sensitive potassium channel subunit, Kv1.2. We have taken advantage of this unique anatomical arrangement offering a high concentration of identified Kv channel subunits by combining whole-cell patch-clamp recording and fluorescence microscopy to establish a novel preparation and perform the first recordings from unambiguously identified mammalian CNS inhibitory presynaptic terminals. We report that DTX-sensitive potassium channels are present in basket cell terminals but not in the basket cell soma. This selective cellular distribution suggests that these channels play an important role in modulating cerebellar inhibitory synaptic transmission.