Glutamine and Other Amino Acid Losses During Continuous Venovenous Hemodiafiltration

Abstract: Serum amino grams and daily losses of glutamine (Gin) and other amino acids (AAs) into diafiltrate were measured during the first 5 days of continuous venovenous hemodiafiltration (CVVHDF) in 6 ICU patients with acute renal failure (ARF). Four patients had ARF as a part of multiple organ failure (MOF) of septic origin, and 2 patients had isolated ARF because of primary renal disease. During the study, all the patients received defined total parenteral nutrition (TPN). The mean daily AA losses into dialysate were relatively low (0.61 ± 0.1 g N ) and reached 4.5% of the daily AA substitution. Gln represented 32.7 ± 5.9% of the total AA losses (0.19 ± 0.04 g N ). Serum levels of Gin (p = 0.002) and of most other AAs were significantly lower in the patients than in the control subjects (AA analysis in 16 healthy volunteers). Phenylalanine (Phe) was the only AA that was increased significantly (p < 0.01) in the patients. The mean patient serum concentrations of Phe and tyrosine were significantly higher (p < 0.03) than the correspondent concentrations in dialysate, but the lysine concentration was higher in dialysate (p < 0.03). The serum and dialysate concentrations of other AAs did not differ. Gin in serum decreased significantly (p < 0.03) on the second day of CVVHDF but returned to the baseline levels subsequently. Serum concentrations of Phe increased on the second day of CVVHDF (p < 0.05). Serum concentrations of other AAs remained stable during the whole study. We conclude that Gin losses into dialysate during CVVHDF are relatively low, but CVVHDF itself may induce changes in Gin metabolism and distribution that are reflected by a decrease of serum Gin levels at the institution of this treatment. Therefore, the need for Gin supplementation in ICU patients is even greater in the first days of CVVHDF.     

Stimulation of glycolysis in Ehrlich ascites carcinoma cells with phenylhydrazonopropanedinitrile and others uncouplers of oxidative phosphorylation

The metabolic consequences of the uncoupling effect of phenylhydrazonopropanedinitrile and others uncouplers of oxidative phosphorylation on Ehrlich ascites carcinoma (EAC) cells were investigated. Upon application of uncouplers in concentrations stimulating the respiration of EAC cells the accelerate glucose uptake and lactate production was observed. The maximal glycolysis stimulation was fourfold in relation to control at the given experimental conditions. Simultaneously the degree of conversion of glucose on lactate was increased. The acceleration of glycolysis was accompanied by stimulation of 14C-labeled adenine and valine incorporation indicating the increased rate of biosynthetic processes. The prolongation of uncoupler action time and application of their higher concentrations cause the inhibition of glycolysis and biosynthetic processes which is evoked with nonspecific effects of the compounds.     

Intrascrotal adenomatoid tumors

Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin. The majority of cases reported have involved the epididymis. We report our experience with 8 cases of testicular tumors and 11 of epididymal adenomatoid tumors during a 13-year period, and review the relevant literature. The incidence of adenomatoid tumors relative to all tumors in the testis was 6.9% (8 of 116), exceeding that of Leydig cell tumors, which were previously believed to be the most common benign testicular neoplasms. The adenomatoid tumors included 38% epididymal tumors (11 of 29). The clinical course of the tumors was benign, without recurrences. Local excision is regarded as the treatment of choice for epididymal and testicular adenomatoid tumors.     

Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.     

Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP)

Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.     

Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats

The effect of bile on the development of 1,2-dimethylhydrazine (DMH)-induced colon cancer was studied in male Wistar rats. Experimental operative models were created, in which in Group 1, the half intestinal tract, the ileum, and the right side of colon were released from bile. In Group 2, both sides of the colon contained bile. The sham operated animals formed Group 3. These techniques changed the concentration of bile acid in different parts of the colon, and the daily total fecal bile acid excretion as well. After DMH treatment, the relationship between these changes of bile acid level and the development of colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the bile acid concentration in the left side of the colon were increased. Our findings show an unambiguous connection between the fecal bile acid level and the incidence of DMH-induced colon cancer.