Extracorporeal shock wave lithotripsy with a transportable mini-lithotripter and subsequent endoscopic treatment improves clinical outcome in obstructive calcific chronic pancreatitis.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) of pancreatic duct stones followed by ERCP with mechanical clearance of the pancreatic duct and subsequent stenting is an established treatment option for chronic calcific pancreatitis. OBJECTIVE: To test the efficacy of a modified transportable mini-lithotripter for ESWL of pancreatic duct stones. DESIGN: Prospective single-center study. SETTING: University hospital. PATIENTS: This study involved 32 patients with obstructive chronic calcific pancreatitis and pain in whom previous endoscopic stone removal and pancreatic duct decompression had failed. INTERVENTIONS: ESWL followed by ERCP for stone clearance of the pancreatic duct and mechanical removal of stones or stenting. MAIN OUTCOME MEASUREMENTS: Endoscopic duct clearance and/or stent insertion, pain and quality-of-life scores. RESULTS: A median of 4 ESWL sessions (interquartile range 2.75-8.5) with a median of 6800 shock waves (4225-15,425) were required. Pain relief after ESWL only was noted in 24 patients (75.0%), whereas no change in the intensity of pain was reported by 7 patients (21.9%), and pain was worse in 1 patient. All patients underwent ERCP and stent placement, resulting in complete resolution of pain in 17 patients (53.1%) and pain improvement in 28 patients (87.5%). The quality-of-life score was significantly improved after ESWL and endoscopic clearance or stenting in all patients. LIMITATIONS: Uncontrolled study. CONCLUSIONS: ESWL with the mini-lithotripter results in fragmentation of pancreatic duct calculi. ESWL in conjunction with endoscopic clearance of the pancreatic duct and stenting is associated with significant improvement in clinical outcome and quality of life in patients with obstructive calcific chronic pancreatitis.

Anti-inflammatory drugs modulate C1q secretion in human peritoneal macrophages in vitro.

The complement system plays an important role in the humoral immune response. Activation of the classical complement pathway is mediated by its subcomponent, C1q, which is involved in the pathogenesis of several autoimmune disorders. Among the main C1q-synthesising tissues, macrophages have been attributed as the main source. We investigated the effects of anti-inflammatory drugs (methylprednisolone and acetylsalicylic acid (ASA)) on C1q secretion in human peritoneal macrophages in vitro. The macrophages were isolated from peritoneal lavage fluid of patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis, and were maintained in culture for up to 6 days. ASA decreased while methylprednisolone increased C1q secretion from human peritoneal macrophages in vitro, which correlated well with the percentage of CD14 positive cells after treatment. We conclude that different response of the macrophages to treatment with methylprednisolone and ASA may point out to the importance of macrophage activation after treatment, as well as an increased abundance of membrane C1q accompanied by increased phagocytosis.

Insufficiently charged isosteric analogue of spermine: interaction with polyamine uptake, and effect on Caco-2 cell growth.

We characterised a novel, charge-insufficient isosteric analogue of spermine, 11-[(amino)oxy]-4,9-diaza-1-aminoundecane (AOSPM). This analogue was synthesised by displacing aminopropyl group by aminooxyethyl group, the latter having pK(a) of about 5. Charge deficiency of the AOSPM molecule was fixed at a definite atom, while pK(a) of the rest nitrogen was similar to the parent polyamine. AOSPM competed with putrescine, spermidine and spermine for the uptake into the cell, and was accumulated in the cells in high amounts when exogenous polyamine synthesis was impaired. It was not recognised by the cells as growth-promoting polyamine, since it was unable to restore growth arrest due to polyamine deprivation. Like natural spermine, this polyamine analogue prevented oxidative DNA damage. AOSPM could be used not only as a tool to study polyamine homeostasis in the cell, but may have distinct applications either as radiation protector, a stable and non-toxic inhibitor of polyamine uptake or, as an appropriate vector, to enhance the uptake of impermeable compounds into the cell.

Ursodeoxycholic acid for treatment of cholestasis in patients with hepatic amyloidosis.

BACKGROUND: Amyloidosis represents a group of different diseases characterized by extracellular accumulation of pathologic fibrillar proteins in various tissues and organs. Severe amyloid deposition in the liver parenchyma has extrahepatic involvement predominantly in the kidney or heart. We evaluated the effect of ursodeoxycholic acid, in four patients with severe hepatic amyloidosis of different etiologies, who presented with increased alkaline phosphatase and gamma-glutamyl transferase. CASE REPORT: The study included four patients who presented with amyloidosis-associated intrahepatic cholestasis. Three of them had renal amyloidosis which developed 1-3 years before cholestasis occurred, the remaining one having intrahepatic cholestasis as the primary sign of the disease. Amyloidosis was identified from liver biopsies in all patients by its specific binding to Congo red and green birefringence in polarized light. The biochemical nature and the class of amyloid deposits were identified immunohistochemically. In addition to their regular treatment, the patients received 750 mg ursodeoxycholic acid per day. After 2-4 weeks all patients had a significant decrease of serum alkaline phosphatase and gamma-glutamyl transferase, and their general status significantly improved. CONCLUSION: Treatment with ursodeoxycholic acid may be beneficial in patients with hepatic amyloidosis, and do extend indications for the use of ursodeoxycholic acid in amyloidotic cholestatic liver disease.

Interleukin-2 in CD8+ T cells correlates with Banff score during organ rejection in liver transplant recipients.

The aim of this study is to compare the histological grading of acute organ rejection according to the Banff score with intracellular interleukin-2 (IL-2) concentrations in cytotoxic CD8+ T cells from peripheral blood samples. 66 recipients after liver transplantation and 20 healthy controls were included into this study. Blood samples of liver transplant recipients were collected beside routine visits or, in case of suspected organ rejection, with additional liver biopsy. For cytometry, the blood cells were stained with CD3, CD8 and intracellular-IL-2. The percentage of cells with detectable intracellular IL-2 was significantly increased in patients with acute rejection (n = 7, P < 0.001, t Test) compared to recipients without rejection. The percentage of cells with detectable intracellular IL-2 (mean +/- SEM) was 7.6 +/- 0.9% in rejection patients, 2.3 +/- 0.22% in stable liver transplant recipients, and 14 +/- 2.99% in healthy controls. Intracellular IL-2 correlates to the Banff score in rejection patients (Spearmans-rho = 0.81, P < 0.05). This cytometric method shows a good sensitivity (71%) with a cut-off based on a high specificity of 95% for histological proven organ rejection in our study cohort. Measurement of intracellular IL-2 in cytotoxic CD8+ T-lymphocytes by flow cytometry correlates very well to the histological grading according to the Banff score and shows a good sensitivity and excellent specificity in acute organ rejection.

[Relationship between physical activity and some parameters of nutritional state in adolescence].

INTRODUCTION: In the last two decades, an increase in obesity along with a number of co-morbidities has been recorded among children and adolescents. OBJECTIVE: The aim was to investigate if there was a difference in nutritional status between adolescents who were active sportsmen and those who did not engage in sport activities other than regular physical activities at school and if active training could be an independent factor in the prevention of obesity. METHODS: There were 117 male adolescents on average aged 15.4 +/- 1.8 years. The subjects were divided into two groups; 32 active sportsmen engaged in regular training in football and a control group consisting of 85 adolescents engaged in no physical activity except for that at school (two hours per week). In all subjects Body Mass Index (BMI) was determined. The percentage of the total body fat was estimated from the sum of values of skin fold thickness measured at four sites (according to Durnin and Womersley). Lean Body Mass (LBM) was estimated by deducting the triceps skin fold from the upper arm circumference and comparing it to the norms. All collected data were analyzed by descriptive and analytical statistical methods: chi2-test, t-test. RESULTS: Adolescent sportsmen showed a statistically significantly lower BMI and percentage of total body fat than the adolescents in the control group (p < 0.01). A significantly higher LBM was found in the sportsmen (p < 0.01). CONCLUSION: Active participation in sports can be a contributing factor in the prevention of obesity, and it is therefore recommended to combine regular physical activities with an adequate diet. BMI screening of general population can indicate a high number of children and adolescents at risk for obesity or who are already obese.

Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate.

BACKGROUND: There is an increasing evidence, stemming from epidemiological studies as well as studies performed in human biopsies and animal and cell culture models, suggesting that folate is chemopreventive in colonic carcinogenesis. Hyperhomocysteinemia is frequently associated with folate deficiency. Homocysteine, an amino acid, is metabolized to methionine in a 5-methyltetrahydrofolate (5-MTHF) dependent reaction. AIM OF THE STUDY: The aim of this study was i) to evaluate the effects of folate and its metabolites on growth and cell cycle progression in human colon cancer cells (Caco-2) in culture, and ii) to assess the effects of exogenous homocysteine on colon cancer cell proliferation. iii) Having found that homocysteine enhances colon cancer cell growth while metabolites of folate inhibit cell proliferation, we investigated the effects of simultaneous treatment in colon cancer cells. METHODS: Caco-2 cells were incubated either with homocysteine (0.1-10 microM), and/or with folic acid and its metabolites (0.625-10 microg/ml). Cell proliferation was determined after 24 h and 48 h by measuring 5- bromo-2'-desoxyuridine (BrdU) incorporation. Additionally, the cells were trypsinized and prepared for cell cycle determination using propidium iodide for DNA staining. The stained cells were analyzed using a flow cytometer. RESULTS: Folate inhibited cell proliferation moderately within 24 h. Its metabolites, dihydrofolate and 5-MTHF were more potent inhibitors of cell growth. Treatment with folate and 5-MTHF resulted in the accumulation of cells in G1-G0 phase of the cell cycle and decreased the number of cells in G2-M phase. In addition, cells treated with 5-MTHF were predominantly accumulated in the S-phase. There was no difference in cell cycle progression of Caco-2 cells treated with homocysteine in comparison to controls. In homocysteine-treated cells, both folate and 5-MTHF reversed the homocysteine-induced enhancement of growth. In contrast, folate reduced the Caco-2 cell growth rate to control values and 5-MTHF depleted growth of homocysteine-treated cells to levels significantly lower than controls. CONCLUSIONS: Our data suggest that 5-MTHF, being the key metabolite in both the folate and homocysteine metabolic pathway, is the main modulator of growth-promoting actions of homocysteine as well as antiproliferative effects of folate in colon cancer cells.