Reversal by ribo- and deoxyribonucleosides of dehydroepiandrosterone-induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation-selection process of experimental carcinogenesis

The effect of dehydroepiandrosterone (DHEA) on the activityof NADPH-producing enzymes and the development of enzyme-alteredfoci has been investigated in the liver of female Wistar ratssubjected to an initiating treatment (a necrogenic dose of diethylnitrosaimine)followed, 15 days later, by a selection treatment [a 15-dayfeeding of a diet containing 0.03% 2-acetylamlnofluorene (2-AAF),with a partial hepatectomy at the midpoint of this feeding].At the end of the selection treatment all rat groups received,for 15 days, a basal diet containing, when indicated, 0.05%phenobarbital (PB) and/or 0.6% DHEA. The effect of DHEA on theactivity of NADPH producing enzymes was also studied in normalrats fed, for 15 days, a diet containing 0.6% DHEA and in theirpair-fed controls. DHEA caused a 43–58% inhibition ofglucose-6-phosphate dehydrogenase (G6PD) and, respectively,338–420% and 21–24% increases in malic enzyme (ME)and isocitric dehydrogenase activities in all rat groups. Thiswas coupled with a great fall in the production of ribulose-5-phosphate,while no change in NADP⁺/NADPH ratio occurred. Hepatocytes,isolated from DHEA-treated rats, exhibited a very low activityof hexose monophosphate shunt (HMS), which was not stimulatedby methylene blue, an exogenous oxidizing agent that markedlystimulated HMS activity in control hepatocytes. DHEA causeda great fall in the percentage of liver occupied by -glutamyltranspeptidase(GGT)-positive foci, in the rats subjected to the initiation- selection treatments. PB enhanced the development of thesefoci, an effect which was completely overcome by DHEA. In addition,focal cells no longer expressed a G6PD activity higher thanthat of surrounding liver in DHEA-treated rats, but exhibiteda high histochemical reaction for ME. DHEA also caused a greatfall in labelling index of GGT-positive foci. Starting at theend of 2-AAF feeding, a mixture of ribonucleosides (RNs) ofadenine, cytosine, guanine and uracil and of deoxyribonucleosides(DRNs) of adenine, cytosine, guanine and thymine were injectedi.p. every 8 h for 12 days to the rats subjected to the initiation- selection treatments plus PB. Rats were killed 3 days afterthe end of RN and DRN treatments. These treatments completelyovercome the DHEA effect on the development of GGT-positivefoci and DNA synthesis by the focal cells, without affectingG6PD activity of both whole liver and putative preneoplasticfoci. Experiments with labeled nucleosides revealed that RNsand DRNs produced derivatives that were incorporated into liverDNA. These data indicate that liver of DHEA-treated rats produceenough NADPH for reduction of RNs to DRNs and growth. The antipromotingeffect of DHEA could depend on a relative deficiency of nudeosidesfor DNA synthesis, caused by a great fall in pentose phosphateproduction.     

Common Exposure to STL Polyomavirus During Childhood

STL polyomavirus (STLPyV) was recently identified in human specimens. To determine seropositivity for STLPyV, we developed an ELISA and screened patient samples from 2 US cities (Denver, Colorado [500]; St. Louis, Missouri [419]). Overall seropositivity was 68%–70%. The age-stratified data suggest that STLPyV infection is widespread and commonly acquired during childhood.     

Effects of morphine on human pancreatic secretion: studies on pure pancreatic juice.

Data concerning the effects of morphine on human pancreatic secretion are fragmentary and inconclusive. In the present study, we evaluated the effects of morphine on pure pancreatic secretion in nine subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Intravenous infusion of a small dose of morphine, 40 microgram/kg/h, during pancreatic stimulation with secretin and cholecystokinin, caused a significant increase in volume, bicarbonate, and calcium secretion, and a significant decrease in protein secretion. The stimulatory effect on water and electrolyte secretion was rapid and much more pronounced, reaching about 45-50% of the control levels, whereas the inhibition of protein output was slightly delayed and of lesser magnitude, reaching about 20-25% of the control values. Both effects were long-lasting. The addition of naloxone, potent opiate antagonist, prevented in part the effects of morphine on pancreatic secretion, suggesting that specific opiate receptors might be involved in these effects.     

Effects of nifedipine GITS and diuretics in isolated systolic hypertension--a subanalysis of the INSIGHT study

Aims: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. Major findings: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. Conclusion: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.     

Elevation of Carbohydrate Antigen 19.9 in Benign Hepatobiliary Conditions and Its Correlation with Serum Bilirubin Concentration

Background Carbohydrate antigen 19.9 (CA19.9), a tumor marker for malignancies of the hepatobiliary tract and pancreas, has frequently been shown to be deranged in a number of non-malignant conditions that are associated with jaundice. This study aims to demonstrate the correlation between CA19.9 and serum bilirubin concentration in patients with benign conditions and to determine the frequency of a false-positive increase in CA19.9 in patients being investigated for potential HPB malignancies. Methods This is a retrospective review of 83 consecutive patients presenting with an abnormal CA19.9 and radiological or clinical features suggestive of HPB malignancy subsequently shown to have benign disease. All patients were thoroughly investigated and followed up until the diagnosis of malignancy could be safely excluded. Results Serum bilirubin, sodium, lymphocyte count, neutrophil:lymphocyte ratio (NLR), β-human chorionic gonadotrophin (HCG), and age were found to correlate with CA19.9 by Pearson’s correlation (P = 0.001, P = 0.006, P = 0.006, P < 0.001, P = 0.012, and P = 0.049, respectively). In multivariate regression analysis, bilirubin was identified as an independent variable that may predict CA19.9 level (P = 0.028). Conclusion CA19.9 level is significantly influenced by serum bilirubin and elevated levels have been observed in patients with non-malignant HPB conditions. Adjusting CA19.9 according to bilirubin levels is likely to improve the specificity of this antigen in the differential diagnosis of benign and malignant HPB diseases and its reliability in the monitoring of disease response to chemotherapy.     

Lymph node pick up by separate stations: Option or necessity

AIM: To evaluate whether lymph node pick up by separate stations could be an indicator of patients submitted to appropriate surgical treatment. METHODS: One thousand two hundred and three consecutive gastric cancer patients submitted to radical resection in 7 general hospitals and for whom no information was available on the extension of lymphatic dissection were included in this retrospective study. RESULTS: Patients were divided into 2 groups: group A, where the stomach specimen was directly formalinfixed and sent to the pathologist, and group B, where lymph nodes were picked up after surgery and fixed for separate stations. Sixty-two point three percent of group A patients showed 16 retrieved lymph nodes compared to 19.4% of group B(P 0.0001). Group B(separate stations) patients had significantly higher survival rates than those in group A [46.1 mo(95%CI: 36.5-56.0) vs 27.7 mo(95%CI: 21.3-31.9); P = 0.0001], independently of T or N stage. In multivariate analysis, group A also showed a higher risk of death than group B(HR = 1.24; 95%CI: 1.05-1.46).CONCLUSION: Separate lymphatic station dissection increases the number of retrieved nodes, leads to better tumor staging, and permits verification of the surgical dissection. The number of dissected stations could potentially be used as an index to evaluate the quality of treatment received.