BACKGROUND: There is no known serum marker for intestinal rejection. Serum concentrations of the amino acid citrulline arise almost exclusively from the intestinal mucosa. We examined the impact of acute cellular rejection (ACR) of intestinal allografts on serum citrulline levels. METHODS: Citrulline concentrations were assayed in serum samples of healthy volunteers (n=6) and seven patients who underwent small bowel transplants (SBTx). Trends in mean citrulline concentrations versus degree of ACR were assessed by matching posttransplantation citrulline concentrations with patients' grade of ACR at time of serum collection. Rejection was confirmed by biopsy and graded by following standardized criteria. An additional patient had citrulline concentrations determined for 31 sequential specimens 3-60 days posttransplant. RESULTS: Mean citrulline concentrations in controls were significantly higher than posttransplantation samples at any rejection grade. Mean concentrations declined significantly as rejection severity increased. The overall downward trend was statistically significant (P<0.05). In sequential measurements, citrulline levels increased significantly over time with declining severity of rejection. The increase in mean citrulline concentration between posttransplant days 3-16 and 52-60 was significant (P<0.01). CONCLUSIONS: Serum citrulline levels decline with increasing grade of ACR and may be a useful serum marker for intestinal rejection.

Adult↗

PubMed2001

Herpes simplex colitis in a child with combined liver and small bowel transplant.

Herpes simplex virus (HSV) has been a rare cause of gastrointestinal (GI) infection, especially in immunocompromised patients. A variety of GI sites may be involved; however, only three reported cases of HSV colitis have been documented in the literature. To our knowledge, this is the first report of HSV colitis in a small bowel transplant recipient.

Colitis↗

PubMed2001

Tacrolimus and diarrhea: pathogenesis of altered metabolism.

Explore the source record for details and available documents.

Diarrhea↗

PubMed2001

Indications for pediatric intestinal transplantation: a position paper of the American Society of Transplantation.

Parenteral nutrition represents standard therapy for children with short bowel syndrome and other causes of intestinal failure. Most infants with short bowel syndrome eventually wean from parenteral nutrition, and most of those who do not wean tolerate parenteral nutrition for protracted periods. However, a subset of children with intestinal failure remaining dependent on parenteral nutrition will develop life-threatening complications arising from therapy. Intestinal transplantation (Tx) can now be recommended for this select group. Life-threatening complications warranting consideration of intestinal Tx include parenteral nutrition-associated liver disease, recurrent sepsis, and threatened loss of central venous access. Because a critical shortage of donor organs exists, waiting times for intestinal Tx are prolonged. Therefore, it is essential that children with life-threatening complications of intestinal failure and parenteral nutrition therapy be identified comparatively early, i.e. in time to receive suitable donor organs before they become critically ill. Children with liver dysfunction should be considered for isolated intestinal Tx before irreversible, advanced bridging fibrosis or cirrhosis supervenes, for which a combined liver and intestinal transplant is necessary. Irreversible liver disease is suggested by hyperbilirubinemia persisting beyond 3-4 months of age combined with features of portal hypertension such as splenomegaly, thrombocytopenia, or prominent superficial abdominal veins; esophageal varices, ascites, and impaired synthetic function are not always present. Death resulting from complications of liver failure is especially common during the wait for a combined liver and intestinal transplant, and survival following combined liver and intestinal Tx is probably lower than following an isolated intestinal transplant. The incidence of morbidity and mortality following intestinal Tx is greater than that following liver or kidney Tx, but long-term survival following intestinal Tx is now at least 50-60%. It is probable that outcomes shall improve in the future with continued refinements in operative technique and post-operative management, including immunosuppression.

Child↗

PubMed2001

Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain.

Addiction to nicotine may result in molecular adaptations in the neurocircuitry of specific brain structures via changes in the cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription program. We therefore investigated the effects of chronic nicotine exposure and its withdrawal on CREB and phosphorylated CREB (p-CREB) protein levels in the rat brain. We report here that chronic nicotine exposure (1-h withdrawal) had no effect on the expression of CREB and p-CREB in the rat cortex and amygdala. On the other hand, decreases in the expression of CREB protein and phosphorylation of CREB occur in the cingulate gyrus, and in the parietal and the piriform but not in the frontal cortex during nicotine withdrawal (18 h) after nicotine exposure. It was also observed that CREB and p-CREB protein levels were significantly decreased in the medial and basolateral, but not in the central amygdala during nicotine withdrawal (18 h) after chronic nicotine exposure. Furthermore, it was found that nicotine withdrawal (18 h) after chronic nicotine exposure leads to decreased CRE-DNA binding without modulating cAMP-dependent protein kinase A activity in the cortex and the amygdala of rats. In addition, chronic nicotine treatment produced anxiolytic effects whereas nicotine withdrawal (18 h) produced anxiety in rats as measured by the elevated plus-maze test. These results provide the first evidence that decreased CREB activity and/or expression in specific cortical and amygdaloid brain structures may be involved in the underlying molecular mechanisms of nicotine dependence.

Amygdala↗

PubMed2001

Effects of chronic ethanol intake and its withdrawal on the expression and phosphorylation of the creb gene transcription factor in rat cortex.

This investigation examined the effects of chronic ethanol treatment (15 days) and its withdrawal (24 h) on the expression and phosphorylation of cyclic AMP-response element-binding (CREB) protein in the rat cortex. The effects of chronic ethanol treatment and withdrawal on protein kinase A (PKA) activity and on the expression of the regulatory RII-beta- and the alpha-subtype catalytic subunits of PKA, and on the protein expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and calcineurin in the rat cortex were also investigated. It was found that ethanol withdrawal but not ethanol treatment produced a significant decrease in the phosphorylated CREB (p-CREB) and CaM kinase IV protein levels in the frontal, parietal, and piriform cortex. Ethanol treatment and its withdrawal had no effect on the protein levels of total CREB in the frontal, parietal, and piriform cortex. On the other hand, ethanol treatment produced a significant reduction in the protein levels of CREB, p-CREB, and CaM kinase IV in the cingulate gyrus, and these changes reverted to normal levels during ethanol withdrawal. Total CREB protein levels were significantly higher in the cingulate gyrus during ethanol withdrawal. It was also observed that mRNA levels of CREB were significantly higher in the rat cortex during ethanol withdrawal but not during ethanol treatment. The protein levels of RII-beta- and alpha-subtype catalytic subunits of PKA and PKA activity were not modified in the rat cortex by chronic ethanol treatment and its withdrawal. Furthermore, the expression of calcineurin in the rat cortex was not altered during ethanol treatment and withdrawal. Taken together, these results suggest the possibility that decreased CREB-dependent events in the neurocircuitry of the frontal, parietal, and piriform cortex may play an important role in the phenomenon of alcohol dependence and also that decreased CREB-dependent events in the neurocircuitry of the cingulate gyrus may play a role in alcohol tolerance.

Animals↗

PubMed2001

Candidemia in neonatal intensive care unit.

The present study was conducted over a period of 6 months to determine the Candida species causing candidemia in a neonatal intensive care unit and to analyse the risk factors associated with acquisition of significant fungemia. Speciation of the 19 isolated Candida spp was done by the standard techniques. Antimicrobial susceptibility of these isolates was determined by disc diffusion method against Amphotericin B, Fluconazole, Ketoconozole and 5-Flucytosine. Candida glabrata was the most common species involved (42.1%). Other species isolated were C. tropicalis (31.6%). Calbicans (21.1%) and C.parapsilosis (5.2%). All the isolates were sensitive to Amphotericin B. Resistance to other antigungal agents was seen only in C. globrata. Significant candidemia was seen in 14/19 (72.6%) of neonates. Risk factors found to be associated with significant candidemis in these neonates included intake of multiple broad-spectrum antibiotics (p<0.0001), use of total parenteral nutrition (p<0.045) and ventilators (p<0.0001).

Amphotericin B↗

PubMed2000

Blockade of cyclic AMP-responsive element DNA binding in the brain of CREB delta/alpha mutant mice.

The cAMP-responsive element binding protein (CREB) gene transcription factor has been implicated in the synaptic plasticity and memory. Here, we investigated the mechanisms of CREB and/or cyclic AMP-responsive element modulatory protein (CREM) binding to CRE sites in brain tissues. CRE-DNA binding was determined in nuclear extracts obtained from the several brain structures of wild-type and CREB delta/alpha mutant mice. It was found that antibodies to CREB, phosphorylated CREB, and CREM supershifted the CRE-DNA binding complex in cortical nuclear extracts from wild-type mice, which suggests that the CRE-DNA binding complex contains both CREB and CREM proteins. In contrast, CRE-DNA binding is abolished in the cortex, hippocampus, cerebellum, and amygdala of CREB delta/alpha mutant mice. Because the CREB delta and alpha isoforms have been deleted in CREB mutant mice, consequently, other forms of CREB, such as CREB-beta and CREM, are up-regulated. These results suggest that the binding of CREM to CRE sites requires the presence of CREB delta/alpha, and that CREB-beta may be inefficient in binding to CRE-sites. Thus, these results indicate that CREB delta/alpha mutant mice are a useful animal model for studying the functional role of CREB-dependent gene expression.

Animals↗

PubMed2000

Otomycosis: a clinicomycologic study.

Otomycosis is a common fungal infection of the ear that is seen in the tropical and subtropical regions of the world. We performed mycologic analyses on debris and scraping samples from the external ear canals of 95 patients who had been clinically diagnosed with otomycosis. Seventy-one samples (74.7%) were positive for fungal growth; two of these samples contained two fungi, bringing the total number of isolates to 73. The most common pathogens were Aspergillus fumigatus (41.1% of all isolates), A niger (36.9%), and Candida albicans (8.2%).

Adult↗

PubMed1999

Neuroadaptational changes in DNA binding of stimulatory protein-1 and nuclear factor-kB gene transcription factors during ethanol dependence.

To define the molecular basis of ethanol dependence, the changes in gene transcription factor stimulatory protein-1 (SP1) and nuclear factor-kB (NF-kB) DNA binding activities were investigated in the rat cortex and hippocampus during ethanol treatment (15 days) and its withdrawal. It was found that both protracted ethanol treatment and its withdrawal (12, 24, or 72 h) had no effect on NF-kB DNA binding activity in the rat cortex and hippocampus. Time-course studies of the changes in SP1 DNA binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after protracted ethanol exposure indicated that SP1 DNA binding in the rat cortex was significantly decreased at 0 h, and that it remained decreased at 12, 24, and 72 h of withdrawal. On the other hand, SP1 DNA binding activity did not change in the rat hippocampus during ethanol treatment but was significantly decreased at 12, 24, and 72 h of withdrawal. These results suggest the possibility that decreased SP1-dependent gene transcription in the rat cortex and hippocampus may be associated with the molecular mechanisms of ethanol dependence.

Adaptation, Physiological↗

PubMed1999

Involvement of the cyclic AMP-responsive element binding protein gene transcription factor in genetic preference for alcohol drinking behavior.

BACKGROUND: Cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding (CREB) protein is a gene transcription factor that can integrate the signals mediated via the cAMP second messenger cascade at the gene expression level, which then controls neuronal functions. METHODS: To examine if the protein kinase A --> CREB signaling cascade is involved in genetic alcohol drinking preference, different measures of CREB were determined in various brain structures of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. RESULTS: We show here that CRE-DNA binding activity is significantly decreased in the amygdala but not in the cortex, hippocampus, or striatum of P rats compared with NP rats. The levels of total CREB and phosphorylated CREB protein in the amygdala are significantly lower in P rats compared with NP rats. On the other hand, levels of the alpha-isoform of the catalytic subunit of protein kinase A protein, and basal as well as cAMP-stimulated protein kinase A activity are similar in the amygdala of both P and NP rats. CONCLUSIONS: Because P and NP rats are genetically bred for high and low alcohol drinking behavior, respectively, these results suggest the possibility that decreased expression of CREB protein in the amygdala may be associated with the high alcohol drinking behavior of P rats.

Activating Transcription Factor 2↗

PubMed1999

Potential role of the gene transcription factor cyclic AMP-responsive element binding protein in ethanol withdrawal-related anxiety.

This investigation examined the effects of acute and chronic ethanol exposure and its withdrawal on the cAMP-responsive element binding protein (CREB) and the activator protein-1 (AP-1) gene transcription factors in the rat brain. The anxiogenic effects of ethanol withdrawal after acute or protracted ethanol treatment of rats were measured by the elevated plus-maze (EPM) test. It was observed that ethanol withdrawal after acute ethanol treatment has no effect on open-arm activity (percent of open-arm entries and the mean percent of time spent on the open arms) of rats on the EPM test. On the other hand, the time course studies of the development of anxiety during ethanol withdrawal (0, 12, 24, and 72 h) after 15 days of ethanol treatment indicate that peak anxiety (significant decrease in open-arm activity) occurred at 24 h of ethanol withdrawal in rats. It was observed that acute ethanol treatment and its withdrawal (24 h) had no effect on CRE- or AP-1 DNA-binding activities in the rat cortex as determined by the electrophoretic gel-mobility shift assay. It was also found that chronic ethanol treatment and its withdrawal (24 h) had no effect on AP-1 DNA-binding activity in the rat cortex. Investigation of the time course studies of changes in CRE-DNA-binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after 15 days of ethanol treatment indicated that the peak reduction of CRE-DNA-binding activity occurred at 24 h of ethanol withdrawal. The changes in the immunolabeling of the CREB-related target, that is, brain-derived neurotrophic factor (BDNF), in the rat cortex during chronic ethanol treatment and its withdrawal (24 h) were examined using western blotting. It was found that 24 h but not 0 h of ethanol withdrawal after 15 days of ethanol treatment caused a significant decrease in the immunolabeling of BDNF in the rat cortex. Fluoxetine (alone) treatment of rats for 1 or 15 days had no effect on open-arm activity and cortical CRE-DNA-binding activity. However, when fluoxetine was administered concurrently with ethanol treatment for 15 days, it caused a reversal of the anxiogenic effects of ethanol withdrawal and antagonized the down-regulation of CRE-DNA-binding activity and of the decrease in immunolabeling of BDNF in the cortices of ethanol-withdrawn rats. On the other hand, acute fluoxetine treatment produced normalization of the reduction of cortical CRE-DNA binding in ethanol-withdrawn rats (24 h) but did not reach the level of significance compared with normal control rats. Acute fluoxetine treatment had no effect on anxiety in ethanol-withdrawn rats. Taken together, these results suggest the possibility that decreased CRE-DNA-binding activity in the rat cortex may be associated with the molecular mechanisms of ethanol dependence (i.e., ethanol withdrawal-related anxiety).

Animals↗