Carcinoma de células claras variedad no hialinizante de parótida: comunicación de dos casos con diferente grado de diferenciación / Non-hyalinizing clear cell carcinoma of the parotid: report of two cases with different grade of differentiation

El carcinoma de células claras es una neoplasia rara de bajo grado que se desarrolla casi exclusivamente en glándulas salivales menores humanas. El objetivo de esta comunicación es analizar las características estructurales, histoquímicas e inmunohistoquímicas (IHQ) de dos casos de carcinoma de células claras de parótida y realizar el diagnóstico diferencial con otros tumores salivales primarios y metastásicos que presentan células claras. Cortes de ambos tumores fueron procesados para H/E, tricrómicos de Masson y Dane, Azul de toluidina, Azul alciano, PAS y PAS/diastasa; marcaciones IHQ para citoqueratinas de bajo y alto peso molecular, ki67, HMB45, p63 y proteína S-100. El patrón estructural de estos tumores estaba determinado por nidos y cordones de células claras delimitados por un estroma no hialinizado. En un tumor se observó una neoplasia maligna a células claras con manifiesta anaplasia. La expresión de ki67 fue importante. El otro tumor estaba constituido por células claras monomorfas sin signos manifiestos de atipia y casi nula expresión de ki67. Con PAS se demostró la presencia de glucógeno y no se observó un desarrollo importante del estroma colágeno en ambas neoplasias. En ambos casos resultó francamente positiva la inmunomarcación para citoqueratinas de bajo y alto peso molecular. Por el contrario resultó negativa para HMB45 y p63. La proteína S-100 tuvo su expresión en células aisladas. Se concluye que los casos presentados son de localización poco común (parótida) según lo descripto en la bibliografía; corresponden a la variedad no hialinizante ya que no está presente un importante estroma colágeno hialinizado, y ambos tumores son primarios de glándulas salivales, de origen epitelial, no melanocítico ni hematopoyético (linfomas) como lo demuestran las marcaciones IHQ.

The clear cell carcinoma is a rare neoplam of low level grade that develops almost exclusively in human minor salivary glands. The objective of this present work is to analyze the structural, histochemical and inmunohistochemical (IHQ) characteristics of two cases of parotid clear cell carcinoma and make a differential diagnosis with other primary and metastatic salivary tumors that clear cells show. Serial cuts of both tumors were processed for H/E, Masson and Dane trichromes, Toluidine blue, Alcian blue, PAS and PAS/diastase; IHQ marking of both high-and low-molecular weight cytokeratins, ki67, HMB45, p63 and S-100 protein. The structural pattern of these tumors were determined by nests and cords of clear cells delimited by a stroma non hyaline. In a tumor a malign neoplasia was observed in clear cells with anaplasia. The ki67 expression was important. The other tumor was constitued of clear monomorph cells without manifestation signs of atypia and almost no ki67 expression. With PAS was confirmed the presence of glycogen and not observed an important development of the collagen stroma in both neoplasms. Both cases resulted very positive the immunostaining of both high and low molecular weight cytokeratins. It resulted negative for the HMB45 and p63. The protein S-100 has it´s expression in isolated cells. We conclude that: the presented cases are very uncommon localization (parotid) as described by the literature; it matches a non hyalinizing variety because a very important hyalinized collagen stroma is not present, both primary tumors of salivary glands, of epithelial origin, non melanocytic, renal or hematopoietic lymphomas which shows immunostaining IHQ.

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes.

BACKGROUND AND AIMS: Metabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity. DESIGN AND METHODS: Eighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated. RESULTS: As expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as >250%ml⁻¹ h⁻¹. The predictive variables of high CETP were non-HDL-C≥160mg/dl (OR=11.1;95%IC=3.3-38.2;p<0.001) and HOMA-IR>2.1 (OR=4.4;95%IC=1.3-14.8;p<0.05). CONCLUSIONS: High non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.

Assessment of the multiple components of the variability in the adenoma detection rate in sigmoidoscopy screening, and lessons for training.

BACKGROUND AND STUDY AIMS: The determinants of the observed variability of adenoma detection rate (ADR) in endoscopy screening have not yet been fully explained. PATIENTS AND METHODS: Between November 1999 and November 2006 13 764 people (7094 men, 6670 women; age range 55-64) underwent screening flexible sigmoidoscopy at five hospital endoscopy units in Turin. To study the determinants of the ADR for distal adenomas, accounting for patient, examiner, and hospital characteristics, we applied a multivariate multilevel regression model. RESULTS: Average ADRs for all adenomas and for advanced adenomas (size > or = 10 mm, villous component > 20 %, high grade dysplasia) were 13.5 % (range 5.2 %-25.0 %) and 6.4 % (3.1 %-10.7 %) for men, and 8.0 % (2.5 %-14.0 %) and 3.7 % (0.2 % - 7.4 %) for women. In multivariate analysis, increased ADR of advanced adenomas was associated with male gender (odds ratio [OR] 1.78, 95 %CI 1.49 - 2.11), self-report of one first-degree relative with colorectal cancer (CRC) (1.44, 1.11-1.86), or of recent-onset rectal bleeding (1.73, 1.24-2.40). Adjusting for these variables, a significantly lower ADR was found for endoscopists with either a lower rate of incomplete sigmoidoscopy (< 9 %; OR 0.59, 95 %CI 0.41-0.87) or a higher rate (> 12 %; 0.64, 0.45-0.91), or with low activity volume (< 85 sigmoidoscopies/year; 0.66, 0.50-0.86). Residual variability explained by the endoscopy center effect was about 1 % and statistically significant. CONCLUSIONS: Endoscopist performance in flexible sigmoidoscopy CRC screening is highly variable. Low volume of screening activity independently predicts lower ADR, suggesting that operators devoting more time to screening sigmoidoscopy may perform better. Variability among pathologists in adenoma classification might explain part of the residual variability across endoscopy units.

Salmonid microarrays identify intestinal genes that reliably monitor P deficiency in rainbow trout aquaculture.

Nutrient-responsive genes can identify important metabolic pathways and evaluate optimal dietary levels. Using a 16K Salmo salar microarray, we identified in rainbow trout (Oncorhynchus mykiss) 21 potential phosphorus (P)-responsive genes, mainly involved in immune response, proteolysis or transport, whose expression levels changed in the intestine after 5 days of feeding a low-P (LP) diet. Diet-induced changes in the expression levels of several genes in each fish were tightly correlated with changes in serum P, and the changes persisted for an additional 15 days after dietary P deficiency. We then evaluated these and previously identified P-responsive genes under simulated farm conditions, and monitored the intestinal gene expression from 6 h to 7 days after the trout were switched from a sufficient-P (SP) diet to a LP diet (SP-->LP), and from a LP diet to a SP diet (LP-->SP). After 7 days, mean serum P decreased 0.14 mM/day for SP-->LP and increased 0.10 mm/day for LP-->SP. The mRNA abundance of the metalloendopeptidase meprin 1alpha (MEP1alpha), the Na(+)-dependent phosphate co-transporter (NaPi2b,SLC34A2), the sulfotransferase SULT2beta1 and carbonic anhydrase XIII genes all increased after SP-->LP and decreased after LP-->SP, suggesting that adaptive expression is reversible and correlated with dietary P. The duration of change in gene expression in response to SP-->LP was generally shorter than that of LP-->SP, suggesting potentially different mechanisms of adaptation to deficiency as opposed to excess. Diet-induced changes in mRNA abundance of other genes were either transient or modest. We identified, by heterologous microarray hybridization, new genes sensitive to perturbations in dietary P, and then showed that these genes can reliably monitor P deficiency under field conditions. Simultaneous changes in the expression of these P biomarkers could predict either P deficiency (to prevent economic losses to the farmers) or P excess (to prevent inadvertent pollution of nearby waters).

Barrett's oesophagus: long-term follow-up after complete ablation with argon plasma coagulation and the factors that determine its recurrence.

BACKGROUND: Argon plasma coagulation seems to be a promising technique for ablation of Barrett's oesophagus, yet few long-term efficacy data are available. AIM: To report on a long-term follow-up and the factors that determine the recurrence of intestinal metaplasia in a cohort of patients with non dysplastic, intestinal type Barrett's oesophagus, after complete ablation of the metaplastic mucosa with argon plasma coagulation. METHODS: Ninety-six patients underwent endoscopic argon plasma coagulation with adequate acid suppression obtained through a continuous omeprazole therapy (50 patients) or through laparoscopic fundoplication (46 patients). Complete ablation was achieved in 94 patients who underwent follow-up. Endoscopic and histological examinations were performed every 12 months. RESULTS: The median follow-up of the patients was 36 months (range 18-98). A recurrence of intestinal metaplasia was found in 17 patients (18%), with an annual recurrence rate of 6.1%. Neither dysplasia, nor adenocarcinoma were found during the follow-up. Through the use of logistic regression analysis, previous laparoscopic fundoplication was associated with a reduced recurrence rate of intestinal metaplasia (odds ratio 0.30, 95% confidence interval 0.10-0.93). CONCLUSIONS: The long-term recurrence of intestinal type Barrett's oesophagus was low after complete ablation with argon plasma coagulation. The control of oesophageal acidity acid exposure with laparoscopic fundoplication seems to reduce the recurrence rate.

Predictive value of rectal bleeding for distal colonic neoplastic lesions in a screened population.

The aim of this study was to determine the diagnostic value of rectal bleeding for distal colorectal cancer (CRC), or large (> or =10 mm) adenomas among an average-risk population. A cross-sectional survey was conducted among individuals aged 55-64 years, who attended sigmoidoscopy (FS) screening in the context of a multicentre randomised trial of FS screening for CRC. Sensitivity, specificity and positive predictive value (PPV) of rectal bleeding for large distal adenomas or CRC were calculated. Rectal bleeding was reported by 8.8% of 8507 patients examined (15% of those with large adenomas and 29% of those with CRC). The risk of CRC was increased when bleeding was associated with an altered bowel habit: odds ratio (OR)=10.42; 95% Confidence Interval (CI): 4.08-26.59; the corresponding OR for isolated bleeding was 5.29 (95% CI: 2.28-12.30). Rectal bleeding carries an increased risk of distal neoplastic lesions. However, most lesions are detected among asymptomatic subjects. This finding suggests that screening represents the optimal strategy to detect CRC or large adenomas in the distal colon in the targeted age range.

Dietary P regulates phosphate transporter expression, phosphatase activity, and effluent P partitioning in trout culture.

Phosphate utilization by fish is an important issue because of its critical roles in fish growth and aquatic environmental pollution. High dietary phosphorus (P) levels typically decrease the efficiency of P utilization, thereby increasing the amount of P excreted as metabolic waste in effluents emanating from rainbow trout aquaculture. In mammals, vitamin D3 is a known regulator of P utilization but in fish, its regulatory role is unclear. Moreover, the effects of dietary P and vitamin D3 on expression of enzymatic and transport systems potentially involved in phosphate utilization are little known. We therefore monitored production of effluent P, levels of plasma vitamin D3 metabolites, as well as expression of phosphatases and the sodium phosphate cotransporter (NaPi2) in trout fed semipu diets that varied in dietary P and vitamin D3 levels. Mean soluble P concentrations varied markedly with dietary P but not with vitamin D3, and constituted 40-70% of total effluent P production by trout. Particulate P concentrations accounted for 25-50% of effluent P production, but did not vary with dietary P or vitamin D3. P in settleable wastes accounted for <10% of effluent P. The stronger effect of dietary P on effluent P levels is paralleled by its striking effects on phosphatases and NaPi2. The mRNA abundance of the intestinal and renal sodium phosphate transporters increased in fish fed low dietary P; vitamin D3 had no effect. Low-P diets reduced plasma phosphate concentrations. Intracellular phytase activity increased but brushborder alkaline phosphatase activity decreased in the intestine, pyloric caeca, and gills of trout fed diets containing low dietary P. Vitamin D3 had no effect on enzyme activities. Moreover, plasma concentrations of 25-hydroxyvitamin D3 and of 1,25-dihydroxyvitamin D3 were unaffected by dietary P and vitamin D3 levels. The major regulator of P metabolism, and ultimately of levels of P in the effluent from trout culture, is dietary P.

Endoscopic ablation of Barrett's esophagus using argon plasma coagulation (APC) following surgical laparoscopic fundoplication.

BACKGROUND: Barrett's esopagus (BE) is considered a risk factor for the development of esophageal carcinoma. Recently, partial restoration of squamous mucosa after ablation of BE with endoscopic techniques has been described. METHODS: From November 1996 to November 1999, 23 patients with histologically proven BE have been treated by endoscopic argon plasma coagulation (APC) following suppression of gastro-esophageal reflux by laparoscopic fundoplication. Histological follow-up after completed ablation ranged from 16 to 45 months (mean, 31.9 months). RESULTS: Histologically, complete squamous reepithelialization was observed in 20/23 patients, whereas a regrowth of a mixed squamous and gastric type mucosa was observed in 1 patient. Small islands of intestinal metaplasia were observed under the neosquamous epithelium in two patients (9%) during follow-up. CONCLUSION: The success rate of APC ablation following laparoscopic antireflux surgery in our series may be as high as 91%. Nevertheless, small islands of intestinal metaplasia under the new squamous epithelium may persist in some patients. In these circumstances, the authors recommend that endoscopic ablation of BE should be confined to controlled clinical trials.

[Differential diagnosis in fibro-osseous lesions of facial bones: report of a case of ossifying fibroma and review of literature]. / Diagnosi differenziale delle lesioni fibro-ossee delle ossa del massiccio facciale: descrizione di un caso clinico di fibroma ossificante e revisione della letteratura.

Ossifying fibroma is a relatively rare, benign neoplasm of non-odontogenic origin, affecting the facial bones, and prevalently localized in the mandible, but which can also appear in the maxilla, paranasal sinuses and peripheral bones. Its growth is generally very slow and it is usually asymptomatic, for which it often manages to reach a considerable size. An incidental diagnosis during orthopantography, on the other hand, is not infrequent. The diagnosis, which is fundamentally made by utilizing conventional x-rays and CT and NMR scans, may present several controversial aspects and is not to be disjointed from the clinical and anatomopathological aspects, for which close interdisciplinary collaboration is required in many cases. In effecting a differential diagnosis, the possibility of inflammatory lesions, other fibrous-osseous lesions (in particular, fibrous dysplasia) and benign or malignant neoplasms must be taken into consideration. The present work presents a case of ossifying fibroma of the maxilla that is emblematic in its clinical, radiological and histopathological aspects. It also discusses problems connected with classification and differential diagnosis, in particular with respect to fibrous dysplasia, which are important in determining the proper therapeutic approach.

Dietary and developmental regulation of intestinal sugar transport.

The Na(+)-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na(+) and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar transport regulation in the small intestine. I close by suggesting specific areas of research that may yield important information about this interesting, but difficult, topic.

Prognostic indicators of local recurrence in patients operated for rectal cancer.

BACKGROUND/AIMS: To identify subgroups of patients at high risk of local relapse after curative surgery for rectal cancer. METHODOLOGY: Thirty-five variables of 216 patients observed from January 1987 to December 1995 were retrospectively analyzed according to univariate and multivariate methods. Median follow-up was 38 months. RESULTS: High and moderate grade (P = 0.0001), Size > or = 5 cm (P = 0.013), lymph nodes involvement (P = 0.002) and patients with locally advanced rectal cancer underwent extensive surgery and postoperative radiation significantly increased local relapse; whereas surgical procedure and experience of surgeons had no influence. CONCLUSIONS: The above-mentioned prognostic factors of rectal cancer that show a risk of local relapse 2- to 3.5-times higher than comparative conditions could be useful in identifying subgroups of patients at high risk for local recurrence. These patients should undergo a careful selection according to risk factors of relapse in order to increase local control of disease performing "optimal" primary surgery, effective postoperative radiation and tailored follow-up.

Intestinal perfusion induces rapid activation of immediate-early genes in weaning rats.

C-fos and c-jun are immediate-early genes (IEGs) that are rapidly expressed after a variety of stimuli. Products of these genes subsequently bind to DNA regulatory elements of target genes to modulate their transcription. In rat small intestine, IEG mRNA expression increases dramatically after refeeding following a 48-h fast. We used an in vivo intestinal perfusion model to test the hypothesis that metabolism of absorbed nutrients stimulates the expression of IEGs. Compared with those of unperfused intestines, IEG mRNA levels increased up to 11 times after intestinal perfusion for 0.3-4 h with Ringer solutions containing high (100 mM) fructose (HF), glucose (HG), or mannitol (HM). Abundance of mRNA returned to preperfusion levels after 8 h. Levels of c-fos and c-jun mRNA and proteins were modest and evenly distributed among enterocytes lining the villi of unperfused intestines. HF and HM perfusion markedly enhanced IEG mRNA expression along the entire villus axis. The perfusion-induced increase in IEG expression was inhibited by actinomycin-D. Luminal perfusion induces transient but dramatic increases in c-fos and c-jun expression in villus enterocytes. Induction does not require metabolizable or absorbable nutrients but may involve de novo gene transcription in cells along the villus.

GLUT-5 expression in neonatal rats: crypt-villus location and age-dependent regulation.

The rat fructose transporter normally appears after completion of weaning but can be precociously induced by early feeding of a high-fructose diet. In this study, the crypt-villus site, the metabolic nature of the signal, and the age dependence of induction were determined. In weaning rats fed high-glucose pellets, GLUT-5 mRNA expression was modest, localized mainly in the upper three-fourths of the villus, and there was little expression in the villus base. When fed high-fructose pellets, GLUT-5 mRNA expression was two to three times greater in all regions except the villus base. Intestinal perfusion in vivo of a nonmetabolizable fructose analog, 3-O-methylfructose, tended to increase fructose uptake rate and moderately increased GLUT-5 mRNA abundance but had no effect on glucose uptake rates and SGLT1 mRNA abundance. Gavage feeding of high-fructose, but not high-glucose, solutions enhanced fructose uptake only in pups > or =14 days, suggesting that GLUT-5 regulation is markedly age dependent. Fructose or its metabolites upregulate GLUT-5 expression in all enterocytes, except those in the crypt and villus base and in pups <14 days old.

Role of magnetic resonance imaging in the staging of gastrointestinal neoplasms.

A concise review is presented of the current applications and techniques of magnetic resonance imaging (MRI) in the field of diagnostic imaging of oncologic disease of the gastrointestinal tract, with a summary of the diagnostic possibilities of MRI in the various types of tumor pathology of the gastrointestinal tract. We conclude with a review of the specific situations in which MRI presents distinct advantages over other diagnostic imaging methods (such as computed tomography and ultrasound).

Lactase synthesis is pretranslationally regulated in protein-deficient pigs fed a protein-sufficient diet.

The in vivo effects of protein malnutrition and protein rehabilitation on lactase phlorizin hydrolase (LPH) synthesis were examined. Five-day-old pigs were fed isocaloric diets containing 10% (deficient, n = 12) or 24% (sufficient, n = 12) protein. After 4 wk, one-half of the animals in each dietary group were infused intravenously with [(13)C(1)]leucine for 6 h, and the jejunum was analyzed for enzyme activity, mRNA abundance, and LPH polypeptide isotopic enrichment. The remaining animals were fed the protein-sufficient diet for 1 wk, and the jejunum was analyzed. Jejunal mass and lactase enzyme activity per jejunum were significantly lower in protein-deficient vs. control animals but returned to normal with rehabilitation. Protein malnutrition did not affect LPH mRNA abundance relative to elongation factor-1alpha, but rehabilitation resulted in a significant increase in LPH mRNA relative abundance. Protein malnutrition significantly lowered the LPH fractional synthesis rate (FSR; %/day), whereas the FSR of LPH in rehabilitated and control animals was similar. These results suggest that protein malnutrition decreases LPH synthesis by altering posttranslational events, whereas the jejunum responds to rehabilitation by increasing LPH mRNA relative abundance, suggesting pretranslational regulation.

Chronic but not acute energy restriction increases intestinal nutrient transport in mice.

Chronic energy restriction (ER) dramatically enhances intestinal absorption of nutrients by aged mice. Do adaptations in nutrient absorption develop only after extended ER or immediately after its initiation? To determine the time course of adaptations, we measured rates of intestinal glucose, fructose and proline transport 1-270 d after initiation of ER (70% of ad libitum) in 3-mo old mice. Mice of the same age that consumed food ad libitum (AL) served as controls; a third group was starved for 1 or 2 d only, to distinguish the effects of acute ER from those of starvation. Acute ER of 1, 2 and 10 d had no effect on nutrient absorption. Starvation significantly decreased intestinal mass per centimeter, thereby reducing transport per centimeter and intestinal absorptive capacity without significantly altering transport per milligram of intestine. ER for 24 d enhanced only fructose uptake, whereas ER for 270 d enhanced uptake of all nutrients by 20-100%. Despite marked differences in body weights, the wet weights of the stomach, small intestine, cecum and large intestine were generally similar in AL and ER mice, suggesting that the gastrointestinal tract was spared during ER. In contrast, the wet weights of the lungs, kidneys, spleen, heart, pancreas and liver each differed by 40-120% between ER and AL mice. Intestinal transport adaptations develop gradually during ER, and the main mechanism underlying these adaptations is a dramatic increase in transport activity per milligram tissue.

[Ultrastructural behavior of interstitial cells innervation during the differentiation of the chick embryo ovary cultured with 17-beta-estradiol]. / Comportamiento ultraestructural de la inervación de las células intersticiales durante la diferenciación del ovario del embrión de pollo cultivado con 17-beta-estradiol.

In a previous work we demonstrated the relationship between nerve fibers and nerve endings and interstitial cells (estrogen-producing cells) from the atrophic right ovary and the medulla in the left functioning ovary during embryogenesis in the chick, in ovo. Besides, the local production of neurotrophins by steroidogenic cells is probably involved in the control of ovarian innervation. The objective of the present study was to analyze ultrastructurally the innervation during the differentiation of chick ovary cultured with 17-beta-estradiol. Explants of right and left ovaries from seven to nineteen days in ovo development were cultured separately for 4 days in MEM (controls) or in the presence of 17-beta-estradiol (problems). In controls the electron microscopic examination of the innervation explants from chick embryo ovaries revealed that the interstitial cells are well innervated. Nerve fibres and nerve endings were observed in close contact with steroid-producing cells, a similar pattern of innervation that those of the fifteen days ovaries in ovo development. Problems cultured from seven days showed nerve fibres and nerve endings at difference to controls. These results in vitro suggest that innervation of the ovaries is controlled by indirect mechanism via the hypothalamic-pituitary system and local production factors. More experiments are necessary to confirm this results.

Developmental reprogramming of rat GLUT-5 requires de novo mRNA and protein synthesis.

Fructose transporter (GLUT-5) expression is low in mid-weaning rat small intestine, increases normally after weaning is completed, and can be precociously induced by premature consumption of a high-fructose (HF) diet. In this study, an in vivo perfusion model was used to determine the mechanisms regulating this substrate-induced reprogramming of GLUT-5 development. HF (100 mM) but not high-glucose (HG) perfusion increased GLUT-5 activity and mRNA abundance. In contrast, HF and HG perfusion had no effect on Na(+)-dependent glucose transporter (SGLT-1) expression but increased c-fos and c-jun expression. Intraperitoneal injection of actinomycin D before intestinal perfusion blocked the HF-induced increase in fructose uptake rate and GLUT-5 mRNA abundance. Actinomycin D also prevented the perfusion-induced increase in c-fos and c-jun mRNA abundance but did not affect glucose uptake rate and SGLT-1 mRNA abundance. Cycloheximide blocked the HF-induced increase in fructose uptake rate but not the increase in GLUT-5 mRNA abundance and had no effect on glucose uptake rate and SGLT-1 mRNA abundance. In neonatal rats, the substrate-induced reprogramming of intestinal fructose transport is likely to involve transcription and translation of the GLUT-5 gene.

Intestinal transport during fasting and malnutrition.

Fasting or malnutrition (FM) has dramatic effects on small intestinal mucosal structure and transport function. Intestinal secretion of ions and fluid is increased by FM both under basal conditions and in response to secretory agonists. Intestinal permeability to ions and macromolecules may also be elevated by FM, which increases the potential for fluid and electrolyte losses and for anaphylactic responses to luminal antigens. Mucosal atrophy induced by FM reduces total intestinal absorption of nutrients, but nutrient absorption normalized to mucosal mass may actually be enhanced by a variety of mechanisms, including increased transporter gene expression, electrochemical gradients, and ratio of mature to immature cells. These observations underscore the value of enteral feeding during health and disease.

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group.

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.