Multidisciplinary management of acute cholecystitis during the COVID-19 pandemic.

The coronavirus disease 2019 pandemic had a major impact on most medical services. Our aim was to assess the outcome of acute cholecystitis during the nationwide lockdown period. All patients admitted to our emergency department for AC were analysed. Patient characteristics, performance status, AC severity, treatment modality and outcome of AC were assessed during the lockdown period (Period II: 1 April 2020-30 November 2021) and compared to a historical control period (Period I: 1 May 2017-31 December 2018). AC admissions increased by 72.8% in Period II. Patients were younger (70 vs. 74 years, p = 0.017) and greater in number in the CCI 1 group (20.4% vs. 11.2%, p = 0.043) in Period II. The unplanned readmission rate (6.3 vs. 0%, p = 0.004) and the gallbladder perforation (GP) rate was higher (18.0 vs. 7.3%, p = 0.006) in Period II. Percutaneous transhepatic gallbladder drainage (PTGBD) was more frequent (24.1 vs. 12.8%, p = 0.012) in Period II. In addition to a drop in patient age and CCI, a significant rise in the prevalence of acute cholecystitis, GP and unplanned readmissions was observed during the nationwide lockdown due to the COVID-19 pandemic. PTGBD was more frequent during this period, whereas successful conservative treatment was less frequent.

Metal-Phenolic Film Coated Quartz Crystal Microbalance as a Selective Sensor for Methanol Detection in Alcoholic Beverages.

The facile real-time monitoring of methyl content in fermented beverages is of fundamental significance in the alcohol and restaurant industry, since as little as 4 mL of methanol entering the blood may cause intoxication or blindness. So far, the practical applicability of available methanol sensors, including the piezoresonance analogs, is somewhat limited to laboratory use due to the complexity and bulkiness of the measuring equipment involving multistep procedures. This article introduces a hydrophobic metal-phenolic film-coated quartz crystal microbalance (MPF-QCM) as a novel streamlined detector of methanol in alcoholic drinks. Unlike other QCM-based alcohol sensors, our device operates under saturated vapor pressure conditions, permitting rapid detection of methyl fractions up to seven times below the tolerable levels in spirits (e.g., whisky) while effectively suppressing the cross-sensitivity to interfering chemical compounds such as water, petroleum ether or ammonium hydroxide. Furthermore, the good surface adhesion of metal-phenolic complexes endows the MPF-QCM with superior long-term stability, contributing to the repeatable and reversible physical sorption of the target analytes. These features, combined with the lack of mass flow controllers, valves and connecting pipes delivering the gas mixture, outline the likelihood for future design of a portable MPF-QCM prototype suitable to point-of-use analysis in drinking establishments.

Is axillary lymph node dissection necessary for positive preoperative aspiration cytology lymph node results?

INTRODUCTION: Based on international guidelines, axillary lymph node dissection (ALND) is recommended in cases of breast cancer if preoperative examinations confirm axillary metastasis. We examined which set of preoperative parameters might render ALND unnecessary. PATIENTS AND METHODS: Preoperative examinations (axillary ultrasound and aspiration cytology) confirmed axillary metastasis in 190 cases out of 2671 patients with breast cancer; primary ALN dissection was performed on these patients with or without prior neoadjuvant therapy. The clinicopathological results were analysed to determine which parameter might predict the presence of no more than 2 or 3 metastatic ALNs. RESULTS: The final histological examination confirmed 1-3 metastatic lymph nodes in ALND samples in 116 cases and over 3 metastatic lymph nodes in 74 cases. For patients receiving neoadjuvant therapy (59 out of the 190 cases), if the size of the primary tumour was 2 cm or smaller and/or the metastatic ALN was 15 mm or smaller, then the patient was likely to have no more than 3 positive ALNs (stage N0-1 disease) (p < 0.001). If the patient did not receive neoadjuvant therapy, stage N2 or N3 disease was very likely. No correlation was found between other clinicopathological characteristics of the tumour and involvement of the ALNs. CONCLUSION: Axillary lymph node dissection is not necessary for selected breast cancer patients with axillary metastasis receiving neoadjuvant therapy. In these cases, sentinel lymph node biopsy with or without radiation therapy and close follow-up may serve as adequate therapy.

Post-transplantation morphological and functional changes in kidneys from expanded criteria donors.

Introduction Despite an increase in the number of cadaver donors and overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. The authors wanted to examine whether differences could exist in the function and/or morphology of transplanted kidneys originated from expanded criteria donors (ECDs) and ideal donors 1 and 5 years after transplantation. Methods Kidney function and histopathologic findings were analyzed and compared 1 and 5 years after transplantation in 97 patients having ECD kidneys and in 178 patients who received ideal donor kidneys (IDK). Results Serum creatinine level was significantly higher (p = 0.001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having ECD kidneys as compared with those with IDK 5 years after transplantation. Morphological changes in the transplanted kidneys, such as tubulitis (p = 0.025) and interstitial inflammation (p = 0.002), were significantly more frequently present in patients with ECD kidneys than in those with IDK 1 year after transplantation. Conclusion Despite an absence of differences in kidney function 1 year after kidney transplantation between patients having ECD and IDK, morphological differences in the transplanted kidneys can be detected between the two groups of patients.

Is intraoperative touch imprint cytology indicated in the surgical treatment of early breast cancers?

INTRODUCTION: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results. METHODS: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 µm; impression smears were evaluated after being stained with hematoxylin eosin. RESULTS: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%. CONCLUSIONS: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer.

Low On-Treatment Platelet Reactivity Predicts Long-Term Risk of Bleeding After Elective PCI.

BACKGROUND: Bleeding after percutaneous coronary interventions (PCI) is an important complication with impact on prognosis. AIM: To evaluate the predictive value of enhanced platelet responsiveness to dual antiplatelet therapy with aspirin and clopidogrel, for bleeding, after elective PCI. METHODS AND RESULTS: We performed multiple electrode aggregometry (MAE) platelet functional tests induced by arachidonic acid (ASPI) and adenosine-diphosphate (ADP) before PCI, and 24 hours after PCI, in 481 elective PCI patients who were followed-up for an average of 15.34 ± 7.19 months. Primary end point was the occurrence of any bleeding, while ischemic major adverse cardiovascular event (MACE) was a secondary endpoint. The incidence of total, BARC ≤ 2, and BARC ≥ 3 bleeding, according to BARC classification, was 19, 18, and 1%, respectively. Groups with any, and BARC ≤ 2 bleeding, had a lower average value of MAE ADP test after 24 hours, compared to the group without bleeding: 45.30 ± 18.63 U versus 50.99 ± 19.01 U; P = 0.005; and 45.75 ± 18.96 U versus 50.99 ± 18.99 U; P = 0.01; respectively. Female gender (HR 2.11; CI 1.37-3.25; P = 0.001), previous myocardial infarction (HR 0.56; CI 0.37-0.85; P = 0.006), lower body mass (HR 0.78; CI 0.62-0.98; P = 0.03), and MAE ADP test after 24 hours (HR 0.75; CI 0.61-0.93; P = 0.009) were the independent predictors for any bleeding by Cox univariate analysis. After adjustment, MAE ADP test after 24 hours, was the only independent predictor for any (HR 0.7; CI 0.56-0.87; P = 0.002), and BARC ≤ 2 (HR 0.71; CI 0.56-0.89; P = 0.003) bleeding, by Cox multivariate analysis. CONCLUSION: MAE ADP test before and after PCI, was associated with any, and BARC ≤ 2 bleeding after elective PCI.

Early histopathological changes in new-onset diabetes after kidney transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is one of the most common complications after kidney transplantation. METHODS: Patients were randomly assigned to receive cyclosporine A-based or tacrolimus-based immunosuppression. Fasting and oral glucose tolerance tests were performed, and the patients were assigned to one of the following 3 groups, on the basis of the results: normal, impaired fasting glucose/impaired glucose tolerance, or NODAT. NODAT developed in 14% of patients receiving cyclosporine A-based immunosuppression and in 26% of patients taking tacrolimus (P = .0002). RESULTS: Albumin levels were similar, but uric acid level (P = .002) and the age of the recipient (P = .003) were significantly different between the diabetic and the normal groups. Evaluation of tissue samples revealed that acute cellular rejection and interstitial fibrosis/tubular atrophy were significantly different in the NODAT group. Changes in the Banff score provided significant difference regarding tubulitis and interstitial inflammation (P = .05). CONCLUSIONS: The pathological effect of new-onset diabetes after kidney transplantation can be detected in the morphology of the renal allograft earlier, before the development of any sign of functional impairment.

International multicenter tool to predict the risk of four or more tumor-positive axillary lymph nodes in breast cancer patients with sentinel node macrometastases.

Recently, many centers have omitted routine axillary lymph node dissection (ALND) after metastatic sentinel node biopsy in breast cancer due to a growing body of literature. However, existing guidelines of adjuvant treatment planning are strongly based on axillary nodal stage. In this study, we aim to develop a novel international multicenter predictive tool to estimate a patient-specific risk of having four or more tumor-positive axillary lymph nodes (ALN) in patients with macrometastatic sentinel node(s) (SN). A series of 675 patients with macrometastatic SN and completion ALND from five European centers were analyzed by logistic regression analysis. A multivariate predictive model was created and validated internally by 367 additional patients and then externally by 760 additional patients from eight different centers. All statistical tests were two-sided. Prevalence of four or more tumor-positive ALN in each center's series (P = 0.010), number of metastatic SNs (P < 0.0001), number of negative SNs (P = 0.003), histological size of the primary tumor (P = 0.020), and extra-capsular extension of SN metastasis (P < 0.0001) were included in the predictive model. The model's area under the receiver operating characteristics curve was 0.766 in the internal validation and 0.774 in external validation. Our novel international multicenter-based predictive tool reliably estimates the risk of four or more axillary metastases after identifying macrometastatic SN(s) in breast cancer. Our tool performs well in internal and external validation, but needs to be further validated in each center before application to clinical use.

Functional and morphological changes in kidneys from marginal donors.

Despite the increased number of cadaver donors and overall organ transplantations, we have observed a dramatic increase in the waiting list. We evaluated transplantations performed using marginal (n = 63) and "ideal" or optimal donors (n = 86). Donor and recipient functional and histopathological data were studied at 1 and 5 years after transplantation. Among the marginal donor group, we investigated whether the age or pre-existent hypertension in the donor showed a strong impact on the functional deterioration of the grafts. Twenty-three graftectomies were performed in marginal, and 39 in ideal recipients (P = .002). Evaluating graft function, at 5 years, we observed the serum creatinine level (P = .0001) and the estimated glomerular filtration rate (P = .003) are significantly different between the two groups. At this time there was a significant difference in the serum creatinine level of patients who were older than the age of 55 years compared with those who showed hypertension (P = .0003). Evaluating morphological changes in the kidneys, acute rejection episodes (P = .0004) and interstitial fibrosis/tubular atrophy (P = .002) were significantly greater among the marginal versus the ideal groups. At 1 year after kidney transplantation, despite no significant difference regarding renal function, they were significant in the histology of marginal versus ideal donor kidneys.

Mental representations of the new organ and posttransplant patients' anxiety as related to kidney function.

Transplant patients' representations of their illness, body, and emotional state significantly influence their recovery. In this study, our primary aim was to examine the possible connections between emotional factors, body and illness representations, and renal function after 58 kidney transplantations. To measure mental representations of transplanted kidneys, we developed a projective drawing test. Other assessment instruments were the Beck Depression Inventory, Spielberger's State and Trait Anxiety Scale, and an in-house questionnaire. We also measured conventional kidney function markers, such as serum creatinine and urea levels. Analysis of our results revealed that patients with higher anxiety levels drew significantly larger kidneys in their projective drawing tests, and displayed significantly higher 10-day creatinine and urea level leading us to consider interrelations of an organ's intrapsychic integration and kidney function. If the graft is not integrated mentally in the body image, the representations of the "foreign body" can be associated with such psycho-neuro-immunologic processes of anxiety, which eventually may lead to adverse physiological effects on kidney function.

Post-transplant diabetes mellitus - risk factors and effects on the function and morphology of the allograft.

The incidence of post-transplant diabetes mellitus and its effects on the kidney allograft function and morphology were assessed. Patients were divided into three groups according to their glucose metabolism. Risk factors for diabetes were first assessed, and then changes in renal function were checked. Morphological changes in the allografts were examined by protocol biopsies. The overall incidence of diabetes was 16%. The development of diabetes was influenced significantly by the body mass index, the body weight and the age of the recipient. The incidence of diabetes was 8.6% in patients on cyclosporine A therapy and 28.8% in those on tacrolimus (p < 0.05). As to the morphology of the kidney, a significantly higher proportion of the biopsies showed severe interstitial fibrosis/tubular atrophy (p = 0.0004) and subclinical acute rejection ( p = 0.001) in the diabetic group compared to the normal one. This clinical study has revealed that the adverse effect of diabetes on the allograft can be detected with protocol biopsy before the manifestation of a functional deterioration.

The relationship of multifocality and tumor burden with various tumor characteristics and survival in early breast cancer.

The presence of multifocality and the aggregate tumor size were retrospectively analysed in a database of 1071 operated breast cancers. Around a quarter of all these cancers involved multiple foci, while a tenth of the total demonstrated more than one invasive focus. Although the multifocal cancers were smaller and more often screen-detected than the unifocal cancers, their aggregate tumor size was larger, and they more frequently displayed casting-type calcifications in the mammogram and HER2 positivity. Lobular histology favoured larger tumor burden. The invasive multifocal cancers were more commonly lymph node-positive than the other tumors. In a subgroup of 584 patients with a median follow-up time of 5 years, the larger size of the invasive tumor, the presence of LVI or lymph node involvement, HER2 positivity and triple negativity were associated with a poorer RFS and OS, while the outcome of screen-detected tumors was superior to that of non-screen-detected or interval cancers. A large tumor size, lymph node positivity and HER2 positive or triple negative phenotypes were independent determinants of a poorer survival rate.

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch.

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.

Multicentre validation of different predictive tools of non-sentinel lymph node involvement in breast cancer.

Sentinel lymph node (SN) biopsy offers the possibility of selective axillary treatment for breast cancer patients, but there are only limited means for the selective treatment of SN-positive patients. Eight predictive models assessing the risk of non-SN involvement in patients with SN metastasis were tested in a multi-institutional setting. Data of 200 consecutive patients with metastatic SNs and axillary lymph node dissection from each of the 5 participating centres were entered into the selected non-SN metastasis predictive tools. There were significant differences between centres in the distribution of most parameters used in the predictive models, including tumour size, type, grade, oestrogen receptor positivity, rate of lymphovascular invasion, proportion of micrometastatic cases and the presence of extracapsular extension of SN metastasis. There were also significant differences in the proportion of cases classified as having low risk of non-SN metastasis. Despite these differences, there were practically no such differences in the sensitivities, specificities and false reassurance rates of the predictive tools. Each predictive tool used in clinical practice for patient and physician decision on further axillary treatment of SN-positive patients may require individual institutional validation; such validation may reveal different predictive tools to be the best in different institutions.

Treatment of subclinical injuries detected by protocol biopsy improves the long-term kidney allograft function: a single center prospective randomized clinical trial.

BACKGROUND: The long-term benefit of early treatment of subclinical disorders detected in kidney allografts by protocol biopsy is controversial. We collected 145 protocol biopsies from 113 recipients for comparison with 51 control patients in a single-center, prospective, randomized trial. METHODS: Ultrasound-guided biopsies were performed in recipients with stable renal function. Samples were taken at 3 (n=66) and/or 12 months (n=79) after transplantation. The biopsies were evaluated according to the Banff scheme, and patients were treated based on the diagnosis. Changes in glomerular filtration rate (GFR) were compared with 51 patients who were randomized as a control group. RESULTS: The findings on 38 samples (29%) were considered to be normal. Based on the pathology findings, such as subclinical acute rejection (n=23), calcineurin inhibitor toxicity (n=28), chronic rejection (n=6), and other specific pathologies (n=23), including polyoma virus nephropathy (n=2), induced treatment among 82 recipients (57%). Significantly better graft function was observed at 3-year follow-up among the biopsy group, compared with controls: GFR = 46.0 ± 13.8 vs 35 ± 15 mL/min (P=.002). The 5-year graft survival was significantly higher in the biopsy (81%) than in the control (55.6%) group (P=.0012). CONCLUSION: Early detection and treatment of subclinical pathologies improved graft function and long-term survival. Protocol biopsies were a valuable tool for posttransplantation management.

Functional and histopathologic changes in renal transplant patients with new-onset diabetes and dyslipidemia.

BACKGROUND: The principal risk factors for cardiovascular mortality posttransplantation are hyperglycemia, hypertriglyceridemia, obesity, and smoking. METHODS: Among 115 patients, we assessed the risk factors for new-onset diabetes (NODM) and dyslipidemia (NODL), and their effects on the function and histopathologic changes in the allografts at 1 year posttransplantation. RESULTS: When evaluating the risk factors and the initial recipient data, we observed a significant difference in age when comparing normal vs NODM patients (P=.004), normal versus NODL patients (P=.002), and normal versus NODL + NODM patients (P=.0001). The difference in body mass index (BMI) was significant when comparing normal with NODM + NODL patients (P=.003). In regard to immunosuppressive therapy, NODM was significantly more frequent among/prescribed tacrolimus (tac; P=.005), whereas subjects who received cyclosporine (CsA) showed a significantly higher incidence of NODL (P=.001). The triglyceride levels were 3.02 ± 1.51 mmol/L among those on CsA versus 2.15 ± 1.57 mmol/L for (P=.004). The difference also proved to be significant for total cholesterol level: 5.43 ± 1.23 mmol/L versus 4.42 ± 1.31 mmol/L respectively (P=.001). In regard to allograft function a significant difference was noted at 1 year after transplantation between the NODM + NODL and the normal group in serum creatinine level (P=.02) as well as the estimated glomerular filtration rate (P=.004). Among diabetic patients, the serum creatinine level measured at posttransplant year 5 was significantly higher than that in 1 year (212.43 vs 147.00 µmol/L; P=.0003). When assessing morphologic changes in the kidney, we observed significantly more frequent interstitial fibrosis/tubular atrophy in all 3 groups compared with normal function patients. CONCLUSION: Our clinical study suggested that at 1 year after transplantation allograft function is already impaired in the presence of both medical conditions (NODM and NODL). However, in regard to morphology, a single condition (NODM or NODL) was sufficient to produce histologic changes in the kidney.

Early microcirculatory changes after ischemic preconditioning and small bowel autotransplantation.

BACKGROUND/AIMS: Ischemia-reperfusion injury contributes to the high complication rate of small bowel transplantation (SBTX). Ischemic preconditioning (IPC) protects against reperfusion injury in several organs, but the IPC-induced microcirculatory reaction in the intestine is unknown. METHODS: We examined the effects of IPC on the macrohemodynamics and graft microcirculation in a canine model of SBTX during a 4-hour reperfusion period. In group 1 SBTX was performed, in group 2 IPC was induced before graft harvesting (ischemia 3 times for 5 min, followed by 10 min of reperfusion). Cardiac index and mesenteric blood flow were measured, and the mucosal microcirculation, villus epithelial thickness and functional capillary density were monitored by orthogonal polarization spectral imaging. Leukocyte-endothelial cell interactions were monitored in the postcapillary venules, with intravital fluorescence microscopy. RESULTS: Reperfusion decreased cardiac index and mesenteric blood flow during reperfusion; IPC significantly improved these changes. Reperfusion was accompanied by decreased functional capillary density and epithelial thickness of the villi and increased leukocyte-endothelial cell interactions. IPC increased functional capillary density, prevented epithelial narrowing and reduced leukocyte rolling and adherence. CONCLUSION: IPC improves the macrohemodynamics and the intestinal microcirculation and reduces leukocyte-mediated tissue injury during reperfusion. IPC can be an effective tool to limit reperfusion injury during SBTX.

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.

OBJECTIVE AND DESIGN: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model. MATERIALS AND SUBJECTS: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0-16-grade Geisinger scoring scale. RESULTS: Acid exposure was followed by a significant decrease in the level of beta-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased beta-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant beta-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone. CONCLUSIONS: The acid-induced transcriptional level downregulation of mucosal beta-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.

The role of the glucocorticoid-dependent mechanism in the progression of sodium taurocholate-induced acute pancreatitis in the rat.

The effects of glucocorticoids on acute pancreatitis (AP) have remained contradictory. The aim of this study was to investigate the time courses of the effects of the exogenous glucocorticoid agonists dexamethasone (DEX) and hydrocortisone (HYD) and a glucocorticoid antagonist (RU-38486) and to characterize the local and systemic responses in AP in rats. The glucocorticoid antagonist and agonists were administered just before AP induction. Serum amylase activity determinations, IL-6 bioassays, pancreatic weight/body weight ratio measurements, and survival analysis were performed. Liver and lung injuries were assessed via neutrophil leukocyte infiltration in myeloperoxidase (MPO) assays, tissue adenosine triphosphate (ATP) level determinations, and histology. In the glucocorticoid agonist groups, the survival rate increased, while the serum amylase level, the IL-6 activity, and the pancreatic weight/body weight ratio decreased significantly as compared with the control and RU-treated groups. AP resulted in significant decreases in tissue ATP levels in both the liver and the lung. In the DEX- or HYD-treated groups, the liver ATP levels were significantly elevated, while both the liver and the lung MPO levels were attenuated as compared with the AP and RU-treated groups. These results suggest that glucocorticoids may play important roles in mitigating the progression of the inflammatory reaction during the early phases of AP.

Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells. The mossy fiber bundle was labeled in the hilus as well as along the entire CA3 area of Ammon's horn. In the human, CART-immunoreactive mossy cells displayed the characteristic thorny excrescences both on their somata and their main dendrites. Axon collaterals of mossy cells could be seen in the hilus and the main axons formed a dense band in the inner molecular layer of the dentate gyrus, suggesting that mossy cells are the principal source of the associational pathway. Granule cells of the dentate gyrus and pyramidal neurons of the human hippocampal formation were devoid of CART peptide immunoreactivity. A few labeled non-pyramidal cells and a large group of strongly immunostained axons of unknown origin were present in all layers of CA1-3. Granule cells are the main excitatory cell population of the dentate gyrus while mossy cells are in a key position in controlling activity of granule cells. The specific location of CART peptide in the dentate granule cells of rodents and in the mossy cells of the human hippocampus may indicate involvement of neuronal circuitry of the dentate gyrus in the memory-related effects of cocaine and amphetamine. Independently of its functional role, CART peptide can be used as a specific marker of human mossy cells and of the dentate associational pathway. The sensitivity of CART peptide to postmortem autolysis may restrict the use of this marker in surgically removed hippocampi or in human brains removed and fixed shortly after death.