The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats.

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.

Mononuclear phagocytic system in acute pancreatitis.

1. Functional alterations of the mononuclear phagocytic system (MPS) may be an important factor in the pathogenesis of infection in acute pancreatitis (AP). In the present study, MPS activity was investigated in rats and hepatic blood flow (HBF) was also determined. 2. A total of 122 male Wistar rats were divided into three groups: 1, AP group (N = 51); 2, sham-operated (SO) (N = 49); 3, intact group (IG) (N = 22). AP was induced by retrograde injection of 0.5 ml of 2.5% sodium taurocholate saline into the main biliopancreatic duct under ketamine chloride anesthesia. SO animals were submitted to the same surgical steps as AP animals except for AP induction. 3. Each experimental group was subdivided into two subgroups. The first subgroup was submitted to the study of MPS activity as follows: each group was injected with colloidal 198Au and liver clearance parameters were determined 2 h (N = 11), 12 h (N = 10) and 24 h (N = 10) later in the AP group, and 2 h (N = 9), 12 h (N = 10) and 24 h (N = 11) later in the SO group. In the second subgroup, HBF was assessed using 131I-bromosulphalein at 2 h (N = 10) and 24 h (N = 10) in the AP group and at 2 h (N = 10) and 24 h (N = 10) in the SO group. The IG was submitted to both radioactive tracer studies. Each animal was used for only one experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Modifications of tissue blood flow in acute pancreatitis.

1. Acute pancreatitis (AP) was induced by ductal injection of 2.5% sodium taurocholate saline solution. Plasma and red blood cell (RBC) volume and visceral organ blood flow were evaluated by a radioisotopic method (51Cr tracers) in 45 adult male Wistar rats (22 submitted to AP and 23 controls) 4 h after AP induction. 51Cr-albumin was used to measure plasma volume and 51Cr-RBC was used to measure RBC volume. 2. Changes in tissue hematocrit reflect alterations in tissue blood flow, since reduction in blood flow increases microvascular erythrocyte sequestration. To evaluate the tissue blood flow, we introduce a "tissue hematocrit index" calculated by relating 51Cr-RBC and 51Cr-albumin specific activities measured in visceral organ biopsies. Application of this index to the control and AP groups showed a decrease in blood flow in all visceral organs of the AP group which was reflected by an increase in tissue hematocrit index (2.5-fold for kidneys, 2-fold for pancreas and lungs, 1.6-fold for liver, and 1.2-fold for spleen). 3. As expected, there was an increase in blood hematocrit and a decrease in plasma volume in the AP group, but there were no significant alterations in RBC volume. However, an unequal decrease in blood flow in various tissues such as kidneys, lungs, pancreas and liver was detected in the AP group. 4. This approach provides an easy and simple way to evaluate possible therapeutic protocols for the treatment of acute pancreatitis by measuring effects on visceral blood flow and plasma and blood volumes.

Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study.

Biliary dyskinesia is frequently encountered in clinical practice and is characterized by pain during or after meals. The present study was designed to assess the action of hymecromone in patients with motor disorders of the bile ducts. One hundred twenty-three patients (36 men and 87 women) were enrolled in the multicenter double-blind placebo-controlled study. The mean age was 60.3 years +/- 14.2 SD. Diagnosis was dyspepsia in 58 patients, dyskinesia in 59, cholelithiasis in five and hepatopathy in one. The patients were divided into two groups. One group (61 patients) was treated with hymecromone (300 mg tablets at a dosage of 1,200 mg/day, 2 tablets midday and evening) and another group (62 patients) was treated with placebo. Treatment lasted for 14 days. Control of dyspepsia and pain symptoms of biliary origin was more marked and constant with hymecromone than with placebo. By the end of the treatment, patients in the hymecromone group showed a 70.3% reduction in intensity of spontaneous abdominal pain, while the placebo group showed a 43.8% reduction. Hymecromone was well accepted by the patients and judged to be effective by the investigator in 88.5% of patients treated. The possibility of using hymecromone in 300-mg tablets in the treatment of motor disorders of the bile ducts is thus confirmed.

[Eosinophilic gastroenteritis. Report of a clinical case]. / La gastroenterite eosinofila. Descrizione di un caso clinico

An unusual case of eosinophilic gastroenteritis is described, together with its differential diagnosis from allergic enteropathy. Numerous biopsies and other instrumental examinations pointed to small intestine as the only site and eosinophilic enteritis as a suitable classification. Disappearance of the clinical symptoms was obtained with corticosteroid management in the space of 6 months.

[Ascites in chronic pancreatitides. Report of 2 cases]. / L'ascite nelle pancreatiti croniche. Descrizione di 2 casi.

2 cases of alcoholic chronic pancreatitis complicated by ascites are described. Both presented a cystic formation in the pancreas. In the first, a direct communication existed between the cystic and peritoneal cavities with passage of pancreatic secretion and serous membrane inflammatory reaction. The literature shows that this mechanism is the one most frequently responsible for ascites in chronic pancreatitis. For diagnosis, demonstration of high amylase and proteins in the ascitic fluid was decisive. Internal drainage of the cyst carried out in one of the two cases resolved the picture.

Blockade of the renin-angiotensin system inhibits growth of colorectal cancer liver metastases in the regenerating liver.

Partial hepatectomy (PH), the preferred option for selected patients with colorectal cancer liver metastases (CRCLM), is associated with 40-80% tumor recurrence rates. Renin-angiotensin system (RAS) blockade inhibits tumor growth and has been suggested to improve liver regeneration. We documented the effect of RAS blockade on tumor growth and liver regeneration in a murine model. CRCLM induction followed by 70% PH was performed on 78 CBA mice. Liver regeneration (days 2, 6) and CRCLM tumor load were measured by liver (and tumor) weights, percentage of CRCLM burden and tumor nodule count (days 16, 21). mRNA expression of the RAS components was characterised. Statistical analysis was performed using 2-independent sample T test or Mann-Whitney test (SPSS). Captopril did not impair liver regeneration. By day 21, Captopril decreased tumor burden (percentage of CRCLM in the liver) (48.7 ± 4.7% control, 24.4 ± 6.2 Captopril; p = 0.008), tumor volume (1046.2 ± 200.2 mm(3), 388.3 ± 150.4; p = 0.02), tumor nodule count per image field (181.1 ± 28.5, 68 ± 17.6; p = 0.005) and tumor angiogenesis (71.8 ± 6.4 vessels/mm(2), 43.1 ± 7.6; p = 0.015) compared to controls. Captopril enhanced tumor apoptosis (1 ± 0.2%, 2.5 ± 0.7; p = 0.028). Liver regeneration and tumor development increased liver ACE levels. Blockade of the RAS effectively retarded CRCLM tumor growth at the late stage of tumor development within the regenerating liver without impeding liver regeneration following PH, via anti-angiogenesis and pro-tumor apoptosis. Captopril may be of therapeutic benefit in patients undergoing PH for CRCLM.

Benign pancreatic hyperenzymemia or Gullo's syndrome.

Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by an abnormal increase in serum pancreatic enzymes in the absence of pancreatic disease. The hyperenzymemia can occur sporadically or in a familial form, and all of the pancreatic enzymes show elevations. Although the condition is persistent, the enzyme elevations fluctuate considerably, even temporarily returning to normal levels at times. In this review the main characteristics of this syndrome are described.

Air in the main pancreatic duct: demonstration with US.

Air in the pancreas--nearly always related to an abscess or a pancreatic fistula--is rarely demonstrated. Over a 3-year period, the authors detected air in the main pancreatic duct with ultrasonography (US) in 11 patients. The ductal caliber was normal in five patients and dilated in six. At US, air in the main pancreatic duct is characterized by strongly echogenic foci or echogenic lines in the duct, casting acoustic shadows or producing reverberation artifacts. It is likely that in patients who have biliary-enteric anastomoses or have undergone sphincterotomy, air in the duct of Wirsung is the result of biliary-pancreatic reflux. In patients who have not undergone such operations, the likely cause of pancreatic gas is duodenal-pancreatic duct reflux. Pancreatic gas may be related to causes other than a pancreatic abscess or fistula; it is therefore important for clinicians to realize that pancreatic ductal gas seen on US images may be secondary to prior surgery or due to sphincter of Oddi dysfunction.

Effect of glucagon on pure human exocrine pancretic secretion.

In this study the inhibitory effect of glucagon on pure exocrine pancreatic secretion obtained by direct drainage of the duct of Wirsung in man is demonstrated. In two experiments carried out during stimulation with secretin and CCK-PZ and in one experiment during secretin stimulation an inhibitory effect on pancreatic secretion was found. This effect was global, affecting both the total volume and the concentration and output of protein and the output of bicarbonate. The greater inhibition, however, occurred in the case of protein.

Cortisol and pancreatic secretion. Observations on pure pancreatic juice.

In view of the conflicting results in the literature, we undertook a study of the effects of intravenous administration of control on the external secretion of the pancreas. The study was carried out in five subjects with external transduodenal drainage of the main pancreatic duct, performed after biliary tract surgery. The intravenous injection of cortisol, 100 mg, during a constant intravenous infusion of secretin and cholecystokinin did not cause any significant change in pancreatic secretion. The results do not confirm previous findings in man indicating an inhibitory effect of glucocorticoids given intravenously on exocrine pancreatic secretion.

Investigation of exocrine pancreatic function by continuous infusion of caerulein and secretin in normal subjects and in chronic pancreatitis.

Exocrine pancreatic function has been evaluated in 24 controls and 29 patients with confirmed chronic pancreatitis by continuous infusion (90 min) of synthetic caerulein, 100 ng/kg/h, plus GIH secretin, 1 CU/kg/h. Mean secretory values of the controls were comparable to those obtained by others using maximal doses of secretin and CCK. Unlike the controls, patients suffering from chronic pancreatitis demonstrated a progressive reduction in secretion during infusion. Thus, the comparison of responses for the final 30-min period gave much clearer and more complete discrimination between normal and abnormal pancreatic function than the preceding 30-min period.