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.

General metabolism of the dimorphic and pathogenic fungus Paracoccidioides brasiliensis

Annotation of the transcriptome of the dimorphic fungus Paracoccidioides brasiliensis has set the grounds for a global understanding of its metabolism in both mycelium and yeast forms. This fungus is able to use the main carbohydrate sources, including starch, and it can store reduced carbons in the form of glycogen and trehalose; these provide energy reserves that are relevant for metabolic adaptation, protection against stress and infectivity mechanisms. The glyoxylate cycle, which is also involved in pathogenicity, is present in this fungus. Classical pathways of lipid biosynthesis and degradation, including those of ketone body and sterol production, are well represented in the database of P. brasiliensis. It is able to synthesize de novo all nucleotides and amino acids, with the sole exception of asparagine, which was confirmed by the fungus growth in minimal medium. Sulfur metabolism, as well as the accessory synthetic pathways of vitamins and co-factors, are likely to exist in this fungus.

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.

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.

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 iv 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 per cent) 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 per cent) (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 per cent in the liver and 17.3 vs 18.6 per cent 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 diffedential tissue accumulation and possible toxicity.

Changes in capillary permeability during severe experimental acute pancreatitis in rats.

Abnormalities of microcirculation are thought to have an important role in the pathogenesis of severe acute pancreatitis (SAP) and in the associated multiple organic failure. We studied changes in capillary permeability during experimental SAP in rats. Necrotizing acute pancreatitis was induced by retrograde injection of sodium taurocholate in pancreatic ducts in rats (n = 30). The animals were distributed in three groups in which the spaces of compartmental distribution as well as the tissue distribution of labeled tracers were evaluated with the use of erythrocytes and albumin tagged with radioactive chromium, apart from determining the volume of total body water. All the studies were carried out four hours after the induction of acute pancreatitis and the administration of radioactive tracers.

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)

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 per cent 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)

Hepatocellular carcinoma. Prognostic factors and survival analysis in 135 Italian patients.

This is a retrospective study to evaluate the history of hepatocellular carcinoma and find the relationship between clinical, biochemical and ultrasonographic features and survival in Italian patients. In 135 consecutive patients median follow-up was 16 months (range 1-66 months) and median survival from the time of diagnosis was 12 months. Univariate analysis showed that individual variables associated with significantly decreased survival included: absence of therapy, Okuda's Stage III, Child-Pugh's Class C, alpha-fetoprotein greater than 400 ng/ml, presence of symptoms, moderate or severe ascites, tumor involving both lobes, mixed internal echo pattern, and multinodular or massive type. Multiple regression analysis (Cox model) revealed that the mixed internal echo pattern of hepatocellular carcinoma, the presence of moderate or severe ascites and Okuda's Stage III were independent predictors of high risk of death. These data can help in selecting patients whose probability of survival is considered high enough to undergo treatment and may be useful for stratifying patients in randomized controlled trials.

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.

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.

Modifications of tissue blood flow in acute pancreatitis

I.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. II.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 "tissuehematocrit index" calculated 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). III.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. IV.This approach provides an easy and simple way to evaluate possible therapeutic protocols for the treatment of acute panreatitis by measuring effects on visceral blood flow and plasma and blood volumes

Feocromocitoma maligno: importância do acompanhamento cintilográfico com I131-meta iodo benzilguanidina (I131-MIBG) / Malignant pheochromocytoma: the importance of a scintigraphic investigation with I131 meta iodo benzylguanidine (MIBG I131)

Os autores apresentam um caso de feocromocitoma rastreado com metaiodobenzilguanidina marcada com 131I (MIBG-131I). Esta metodologia identifica a lesäo primitiva, sua recorrência e sua metastatizaçäo. Säo apontadas as vantagens do ensaio pela sua especificidade, sensibilidade e inoqüidade, oferecendo informaçöes ímpares de natureza morfofuncional no diagnóstico e acompanhamento evolutivo dessa doença

Action of secretin on pancreatic enzyme secretion in man. Studies on pure pancreatic juice.

The action of pure, natural secretin on the pancreatic secretion of enzymes was investigated in six patients with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Secretin infused for five successive 50 minute periods at increasing doses of 0.03, 0.1, 0.3, 0.9 and 2.7 clinical units (CU)/kg/h, produce a dose dependent increase in protein and lipase output. A weak but significant (p less than 0.02) increase of enzyme output above the fasting level was already observed with the lowest dose. The maximal output of protein and lipase, observed with the highest dose of secretin infused, corresponded to about 50% of that induced by maximal doses of cerulein (100 ng/kg/h) plus secretin (1 CU/kg/h). As far as bicarbonate is concerned, the lowest dose of secretin (0.03 CU/kg/h) significantly (p less than 0.001) stimulated bicarbonate output. The dose of 0.9 CU/kg/h of secretin evoked a bicarbonate output of 526 +/- 49 micromol/min; trebling the dose of secretin did not significantly increase the output of bicarbonate above this value. Increasing doses of secretin induced a dose related increase in calcium output. There was a close parallel between calcium and protein outputs, suggesting that the increase in calcium output reflected primarily an increase in the enzyme-associated fraction of pancreatic juice calcium. It is concluded that secretin stimulates pancreatic enzyme secretion in man probably by a direct action on the acinar cells.

Analise perinatal de 1017 recem-nascidos com peso superior a 1000g na Maternidade Mario Totta, no ano de 1982. / Perinatal analysis of 1017 newborn infants weighting more than 1000g at the Maternidade Mario Totta, in 1982

Na Maternidade Mario Totta, durante o ano de 1982, ocorreram 5077 partos. Desses, mediante amostra aleatoria sistematica, foram analisadas 1000 gestantes e seus 1017 recem-nascidos cujo peso excedeu a 1000g. Os resultados mostraram uma frequencia de gestacao de alto risco de 33,1% uma incidencia de cesariana de 13%, uma taxa de mortalidade materna de 1% e mortalidade neonatal precoce de 10,82%. As patologias principais envolvidas na morbidade e mortalidade neonatal foram respectivamente as infeccoes e a membrana hialina.Os fatores de risco mais significativos na mortalidade neonatal precoce foram a gestacao de alto risco, a prematuridade, o baixo peso e a depressao ao nascer. Ha necessidade, ainda, de uma assistencia perinatal mais adequada visando ao diagnostico precoce, prevencao e tratamento desses fatores de risco para reducao da mortalidade neonatal